Hematology ......,...yghjjgf dikh du yr wo tho of du
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About This Presentation
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Slide Content
Dr. Azam's
Notes in Anesthesiology
Updated up to December 2013, 3rd Edition
Hematology
Edited by:
Dr. Azam
Consultant Anesthesiologist
8. Critical Care Specialist
www.drazam.com
Notes in Anesthesiology
Updated up to December 2013, 3rd Edition
Hematology
Edited by:
Dr. Azam
Consultant Anesthesiologist
8. Critical Care Specialist
www.drazam.com
Dr Azamı's Notes in Anesthesiology 2013
Dedication
To Mohammed Shafiulla, my father, my oxygen, companion, and best friend; for
being my major pillar of support and making this vision a reality. Thank you for your
continual sacrifices with boundless love and limitless gratitude, for the sake of your
children. I owe you a debt I can never repay.
T also would like to thank my mom (Naaz Shafi), my wife (Roohi Azam), my two lovely
kids (Falaq Zohaa & Mohammed Izaan), for their support, ideas, patience, and
encouragement during the many hours of writing this book.
Finally, I would like to thank my teachers (Dr.Manjunath Jajoor & team) & Dr T. A. Patil. The
dream begins with a teacher who believes in you, who tugs and pushes and leads you to the next
plateau, sometimes poking you with a sharp stick called "truth."
Dr Azam's Notes in Anesthesiology 2013
Dedication
To Mohammed Shafiulla, my father, my oxygen, companion, and best friend; for
being my major pillar of support and making this vision a reality. Thank you for your
continual sacrifices with boundless love and limitless gratitude, for the sake of your
children. I owe you a debt I can never repay.
T also would like to thank my mom (Naaz Shafi), my wife (Roohi Azam), my two lovely
kids (Falaq Zohaa & Mohammed Izaan), for their support, ideas, patience, and
encouragement during the many hours of writing this book.
Finally, I would like to thank my teachers (Dr.Manjunath Jajoor & team) & Dr T. A. Patil. The
dream begins with a teacher who believes in you, who tugs and pushes and leads you to the next
plateau, sometimes poking you with a sharp stick called "truth."
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
ANOTE TO THE READER
Anesthesiology is an ever-changing field. Standard safety precautions must be followed, but as new research and clinical experience
broaden our knowledge, changes in treatment and drug therapy may become necessary or appropriate. Readers are advised to check the
most current product information provided by the manufacturer of each drug to be administered to verify the recommended dose, the
method and duration of administration, and contraindications.
However, in view of the possibility of human error or changes in medical sciences, neither the author nor the publisher nor any other party
who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect
accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information
contained in this work. Readers are encouraged to confirm the information contained herein with other sources. It is the responsibility of the
licensed prescriber, relying on experience and knowledge of the patient, to determine dosages and the best treatment for each individual
patient. Neither the publisher nor the editor assumes any liability for any injury and/or damage to persons or property arising from this
publication.
Dr. Azam
Dr Azam's Notes in Anesthesiology 2013
ANOTE TO THE READER
Anesthesiology is an ever-changing field. Standard safety precautions must be followed, but as new research and clinical experience
broaden our knowledge, changes in treatment and drug therapy may become necessary or appropriate. Readers are advised to check the
most current product information provided by the manufacturer of each drug to be administered to verify the recommended dose, the
method and duration of administration, and contraindications.
However, in view of the possibility of human error or changes in medical sciences, neither the author nor the publisher nor any other party
who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect
accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information
contained in this work. Readers are encouraged to confirm the information contained herein with other sources. It is the responsibility of the
licensed prescriber, relying on experience and knowledge of the patient, to determine dosages and the best treatment for each individual
patient. Neither the publisher nor the editor assumes any liability for any injury and/or damage to persons or property arising from this
publication.
Dr. Azam
Dr Azam's Notes in Anesthesiology 2013
[Contents Dr Azants Notes in Anesthesiology 2013
1. Blood & Blood Products - 6 25. Coagulation & Anesthesia - 79
2. Development of Red Blood Cells - 12 26. Hemophilia - 90
3. Blood Group system - 13 27. Coagulation Factors - 96
4. Blood storage System - 14 28. Artificial BloodBlood Substitutes - 97
5. Recommendation of Blood transfusion - 16 29.What is recombinant factor Vila? Describe the clinical usage of it - 99
6. Compatibility Testing - 17
7. Blood Component therapy & Blood substitutes - 18
8. Define Massive blood transfusion. Discuss the complications
associated with massive blood transfusion - 24 & 71
9. Describe Anesthetics concerns for regional anesthesia in a
patient on anticoagulants - 28
10. What is Disseminated intravascular coagulation? Enumerate its
causes and management - 30
11.Enumerate the indications of packed red cells, fresh frozen
plasma(FFP), platelets & cryoprecipitates - 33
12.Wiite the blood conservative strategies in a 20 year old female
scheduled for excision of angiofibroma of nose - 35
13. Autologus Blood transfusion - 37 & 63
14.Replacement therapy for coagulation factor deficiency - 41
15.Partial thromboplastin time - PTT - 42
16. Activated Clotting Time - ACT - 43
17.Prothrombin Time - PT - 44
18. Describe the coagulation factors. How do you investigate a
case of intra operative coagulopathy - 45
19. Categorization of coagulation disorders - 47
20. Describe various test used for monitoring peri-operative
coagulation - 48
21. Thromboelastography - 51
22. Assessment of blood Loss during Surgery - 53
23. Sickle Cell Anemia & Anesthesia - 55
24. Anemia & Anesthesia - 59
Dr Azam's Notes in Anesthesiology 2013
1. Blood & Blood Products - 6 25. Coagulation & Anesthesia - 79
2. Development of Red Blood Cells - 12 26. Hemophilia - 90
3. Blood Group system - 13 27. Coagulation Factors - 96
4. Blood storage System - 14 28. Artificial BloodBlood Substitutes - 97
5. Recommendation of Blood transfusion - 16 29.What is recombinant factor Vila? Describe the clinical usage of it - 99
6. Compatibility Testing - 17
7. Blood Component therapy & Blood substitutes - 18
8. Define Massive blood transfusion. Discuss the complications
associated with massive blood transfusion - 24 & 71
9. Describe Anesthetics concerns for regional anesthesia in a
patient on anticoagulants - 28
10. What is Disseminated intravascular coagulation? Enumerate its
causes and management - 30
11.Enumerate the indications of packed red cells, fresh frozen
plasma(FFP), platelets & cryoprecipitates - 33
12.Wiite the blood conservative strategies in a 20 year old female
scheduled for excision of angiofibroma of nose - 35
13. Autologus Blood transfusion - 37 & 63
14.Replacement therapy for coagulation factor deficiency - 41
15.Partial thromboplastin time - PTT - 42
16. Activated Clotting Time - ACT - 43
17.Prothrombin Time - PT - 44
18. Describe the coagulation factors. How do you investigate a
case of intra operative coagulopathy - 45
19. Categorization of coagulation disorders - 47
20. Describe various test used for monitoring peri-operative
coagulation - 48
21. Thromboelastography - 51
22. Assessment of blood Loss during Surgery - 53
23. Sickle Cell Anemia & Anesthesia - 55
24. Anemia & Anesthesia - 59
Dr Azam's Notes in Anesthesiology 2013
1. Blood & Blood Products.
History:
+ 1616 - William Harvey - circulations of blood
+ 1818 — James Blundell - man to man transfusion
+ 1874 — William Hagumore- suggested autologous blood
transfusion
+ 1899 — Shaltock — noticed agglutination
+ 1900 - LANSTEINER — described ABO grouping
+ 1902 - Decastello and Sturli - described AB blood group
+ 1916 - Rous and Tume — preservation of blood
+ Oswald Robertson first blood bank
+ 1936 — Levine and stetson — Rh. system
Blood:
+ Blood consists of a fluid medium, plasma, in which are
suspended a number of circulating cells each with its own
highly specialized functions.
‘Site of blood formation:
+ Production of blood cells commences in the yolk sac of the
‘embryo, but then shifts to the liver and to a lesser extent the
spleen, so that these organs become the dominant site of
production between the 2nd and 8th month of gestation.
+ The liver and spleen are then supersede by the bone marrow
which serves as the only important site of blood cell
production after birth
+ Hematopoietic tissue fills all the cavities within the bones of
the newbom, but with increasing age becomes localized in
the cavities of upper shafts of the femur, humerus, the pelvis,
spine, skull and bones of the thorax- this is referred to as red
marrow because of its macroscopic appearance and its total
volume is 1-2 liters.
+ The remaining bone marrow in the more peripheral regions
of the skeleton contains predominantly fat, and is termed as
YELLOW MARROW. It also occupies a volume of 1-2 liters
and serves as a space into which hematopoietic tissue can
‘expand in response to an increased demand for blood cell
production,
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ Only in pathological situations significant hematopoietic activity ocour in
liver, spleen and other sites during adult life and is referred to as
‘extramedullary hematopoesis.
Development of blood cells:
+ Blood cells develop from a small population of TOTIPOTENT
hematopoietic STEM CELLS which maintain their numbers by self
replication and also gives rise to precursors of one or other of the
various blood cells series and cells of the immune system.
paris Mature stage
Progenitor celts TAymphocytes
Se
SELF REPUCATING
TOTIPOTENT STEM
aus
Eiythroidseries -enthrocytes
Metronet
tuve mace =
Koc” matin
stp re-send
opie
Eosinophil series ~ segmented
Eosinophils
Granvlocytes
Bosophilseries- segmented
Bosophils
“Romonovsky stains
History:
+ 1616 - William Harvey - circulations of blood
+ 1818 — James Blundell - man to man transfusion
+ 1874 — William Hagumore- suggested autologous blood
transfusion
+ 1899 — Shaltock — noticed agglutination
+ 1900 - LANSTEINER — described ABO grouping
+ 1902 - Decastello and Sturli - described AB blood group
+ 1916 - Rous and Tume — preservation of blood
+ Oswald Robertson first blood bank
+ 1936 — Levine and stetson — Rh. system
Blood:
+ Blood consists of a fluid medium, plasma, in which are
suspended a number of circulating cells each with its own
highly specialized functions.
‘Site of blood formation:
+ Production of blood cells commences in the yolk sac of the
‘embryo, but then shifts to the liver and to a lesser extent the
spleen, so that these organs become the dominant site of
production between the 2nd and 8th month of gestation.
+ The liver and spleen are then supersede by the bone marrow
which serves as the only important site of blood cell
production after birth
+ Hematopoietic tissue fills all the cavities within the bones of
the newbom, but with increasing age becomes localized in
the cavities of upper shafts of the femur, humerus, the pelvis,
spine, skull and bones of the thorax- this is referred to as red
marrow because of its macroscopic appearance and its total
volume is 1-2 liters.
+ The remaining bone marrow in the more peripheral regions
of the skeleton contains predominantly fat, and is termed as
YELLOW MARROW. It also occupies a volume of 1-2 liters
and serves as a space into which hematopoietic tissue can
‘expand in response to an increased demand for blood cell
production,
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ Only in pathological situations significant hematopoietic activity ocour in
liver, spleen and other sites during adult life and is referred to as
‘extramedullary hematopoesis.
Development of blood cells:
+ Blood cells develop from a small population of TOTIPOTENT
hematopoietic STEM CELLS which maintain their numbers by self
replication and also gives rise to precursors of one or other of the
various blood cells series and cells of the immune system.
paris Mature stage
Progenitor celts TAymphocytes
Se
SELF REPUCATING
TOTIPOTENT STEM
aus
Eiythroidseries -enthrocytes
Metronet
tuve mace =
Koc” matin
stp re-send
opie
Eosinophil series ~ segmented
Eosinophils
Granvlocytes
Bosophilseries- segmented
Bosophils
“Romonovsky stains
Blood & Blood Products.Continuation:
White Cells:
+ Normal white cell count: 4-11 x 10° /1it
+ White cells count in infancy and childhood tend to be greater
than in adults, with values as high as 25 x 10° /lit at birth. After
1% week of life the count drops to 14 x 10° lit
+ The leukocyte count undergoes minor degree of diumal variation
with slight increases in the afternoon
+ Values of upto 15 x 109 /lit are common during pregnancy,
following parturition the count may rise to 20 x 109/lit retuming
to normal values within a week.
Normal values for the cellular elements in human blood:
Cell Normal range | Percentage
Total WEC 4000-11,000
Granulocytes
Neutrophils 3000-6000 50-70%
Eosinophils 150-300 14%
Basophils 0-100 04%
Lymphocytes 1500-4000 20-40%
Monocytes 300-500 28%
Erythrocytes
Females 48x10
Males 5.4 x 105
Platelets | 200,000-500,000
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
Blood Volume:
+ For normal subjects can be estimated in relation to height and
weight.
RBC volume:
+ Men: 26-33 ml/kg
+ Women: 22-29 ml/kg
+ Plasma volume: 35-45 ml/kg
Total blood volume:
+ TOmlkg - adults
+ 80ml/kg — children
+ 90ml/kg - neonates
+ Total blood volume = plasma vol x 100
100 - Hematocrit
Distribution of blood:
+ 60-70% venous
+ 15% arteries
+ 10% in the heart
+ 5% capillary
Blood group and blood transfusion:
Introduction:
The anesthesiologist has to frequently use blood or blood products in
treating the shocked or bleeding patient. The importance of
recognizing adverse reactions associated with transfusion therapy is
‘emphasized by the estimate that over half of all transfusions of blood
products are given during anesthesia. Hence knowledge of blood
groups and transfusion reactions are very important for the
anesthesiologist.
Blood groups:
+ Human RBC contains on their surface a series of glycoproteins and
glycolipids which constitute the blood group antigens also called
agglutinogen. They appear early in fetal lite and remain unchanged
until death. On the basis of these antigens, at least 15 well defined
blood group, systems have been described, They are the ABO, MN,
P, Rh, Lutheran, kell, Kidd, Lewis, Duffy, Diego, YE, Xg, Li, Dombrock
and cotton systems; of these only ABO and Rh systems one of major
clinical importance. 7
White Cells:
+ Normal white cell count: 4-11 x 10° /1it
+ White cells count in infancy and childhood tend to be greater
than in adults, with values as high as 25 x 10° /lit at birth. After
1% week of life the count drops to 14 x 10° lit
+ The leukocyte count undergoes minor degree of diumal variation
with slight increases in the afternoon
+ Values of upto 15 x 109 /lit are common during pregnancy,
following parturition the count may rise to 20 x 109/lit retuming
to normal values within a week.
Normal values for the cellular elements in human blood:
Cell Normal range | Percentage
Total WEC 4000-11,000
Granulocytes
Neutrophils 3000-6000 50-70%
Eosinophils 150-300 14%
Basophils 0-100 04%
Lymphocytes 1500-4000 20-40%
Monocytes 300-500 28%
Erythrocytes
Females 48x10
Males 5.4 x 105
Platelets | 200,000-500,000
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
Blood Volume:
+ For normal subjects can be estimated in relation to height and
weight.
RBC volume:
+ Men: 26-33 ml/kg
+ Women: 22-29 ml/kg
+ Plasma volume: 35-45 ml/kg
Total blood volume:
+ TOmlkg - adults
+ 80ml/kg — children
+ 90ml/kg - neonates
+ Total blood volume = plasma vol x 100
100 - Hematocrit
Distribution of blood:
+ 60-70% venous
+ 15% arteries
+ 10% in the heart
+ 5% capillary
Blood group and blood transfusion:
Introduction:
The anesthesiologist has to frequently use blood or blood products in
treating the shocked or bleeding patient. The importance of
recognizing adverse reactions associated with transfusion therapy is
‘emphasized by the estimate that over half of all transfusions of blood
products are given during anesthesia. Hence knowledge of blood
groups and transfusion reactions are very important for the
anesthesiologist.
Blood groups:
+ Human RBC contains on their surface a series of glycoproteins and
glycolipids which constitute the blood group antigens also called
agglutinogen. They appear early in fetal lite and remain unchanged
until death. On the basis of these antigens, at least 15 well defined
blood group, systems have been described, They are the ABO, MN,
P, Rh, Lutheran, kell, Kidd, Lewis, Duffy, Diego, YE, Xg, Li, Dombrock
and cotton systems; of these only ABO and Rh systems one of major
clinical importance. 7
Blood & Blood Products.Continuation:
Blood group systems:
1) ABO system:
+ Aand B antigens are inherited as Mendelian dominants, and
individuals are divided into 4 major blood types on this basis.
+ Type A individuals have A ag on the RBCs
+ Type B individuals have B ag
+ Type AB individuals have both antigens
+ Type O individuals have neither
Several subgroups of A exist; the most important being A1 and Az.
+ The difference between A; and Az appears to be quantitative
Each A; cell has about 1,000,000 copies of the A ag on its
surface and each A? cell has about 250,000.
+ The A and B antigens are found in many tissues in addition to
blood these include salivary glands, saliva, pancreas, kidney,
liver, lungs, testes, semen and amniotic fluid.
+ Antibodies against red cell agglutinogen are called agglutinins.
+ The serum of an individual contains antibodies against the Ags
lacking on the persons red cells. Thus type A individuals develop
anti B antibodies; type B individuals develop anti A abs, type O
individuals develop both, type AB individuals develop neither.
2) The Rh group:
+ The Rhesus (Rh) blood group system was first demonstrated in
humans, by the use of an antiserum prepared by immunizing
rabbits with red cells from a rhesus monkey. it was found that
some human red cells were agglutinated by the serum “Rh +ve
cells” - while others were not - "Rh -ve cells’. This system is
composed primarily of C, D and E antigens of which Dis the
most important antigenic component and the term “Rh positive”
means that the individual has the D antigen and “th -ve" means
that the individual has no D antigen.
+ Over 99% of Asians are D +ve. Unlike the antibodies of the ABO
system anti-D abs do not develop without exposure of a D -ve
individual to D +ve red cells by transfusion or entrance of fetal
blood into the maternal circulation.
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
Storage of Blood:
+ Several different preservative solutions can be added to either whole
blood or packed RBCs to allow storage of these products.
+ In general preservative solutions contain additives that
a) Prevent coagulation
b) Support glycolysis
(©) Maintain ATP generation
+ The preservative determines the blood products storage on shelf lie,
The duration of storage is determined by the requirement that at
least 70% of the transfused red blood cells remain in circulation for
24 hrs after infusion.
+ Aunit of whole blood generally contains 450m! (+ 10%) of blood and
about 60m! of preservative.
The various preservatives are:
ACD (acid citrate dextrose)
+ Trisodium citrate = 2.2gm A
+ Citric acid = 0.8gmidl
+ Dextrose
+ Water upto = 100m!
+ pH =5.0-5.1
+ 67.5ml ACD is mixed with 420-450m! of blood duration of storage =
gm al
21 days
Preservatives:
+ Acid citrate dextrose (ACD) -21 days
+ Citrate phosphate dextrose (CPD) -28 days
+ CPD + adenine - 35 days
Blood group systems:
1) ABO system:
+ Aand B antigens are inherited as Mendelian dominants, and
individuals are divided into 4 major blood types on this basis.
+ Type A individuals have A ag on the RBCs
+ Type B individuals have B ag
+ Type AB individuals have both antigens
+ Type O individuals have neither
Several subgroups of A exist; the most important being A1 and Az.
+ The difference between A; and Az appears to be quantitative
Each A; cell has about 1,000,000 copies of the A ag on its
surface and each A? cell has about 250,000.
+ The A and B antigens are found in many tissues in addition to
blood these include salivary glands, saliva, pancreas, kidney,
liver, lungs, testes, semen and amniotic fluid.
+ Antibodies against red cell agglutinogen are called agglutinins.
+ The serum of an individual contains antibodies against the Ags
lacking on the persons red cells. Thus type A individuals develop
anti B antibodies; type B individuals develop anti A abs, type O
individuals develop both, type AB individuals develop neither.
2) The Rh group:
+ The Rhesus (Rh) blood group system was first demonstrated in
humans, by the use of an antiserum prepared by immunizing
rabbits with red cells from a rhesus monkey. it was found that
some human red cells were agglutinated by the serum “Rh +ve
cells” - while others were not - "Rh -ve cells’. This system is
composed primarily of C, D and E antigens of which Dis the
most important antigenic component and the term “Rh positive”
means that the individual has the D antigen and “th -ve" means
that the individual has no D antigen.
+ Over 99% of Asians are D +ve. Unlike the antibodies of the ABO
system anti-D abs do not develop without exposure of a D -ve
individual to D +ve red cells by transfusion or entrance of fetal
blood into the maternal circulation.
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
Storage of Blood:
+ Several different preservative solutions can be added to either whole
blood or packed RBCs to allow storage of these products.
+ In general preservative solutions contain additives that
a) Prevent coagulation
b) Support glycolysis
(©) Maintain ATP generation
+ The preservative determines the blood products storage on shelf lie,
The duration of storage is determined by the requirement that at
least 70% of the transfused red blood cells remain in circulation for
24 hrs after infusion.
+ Aunit of whole blood generally contains 450m! (+ 10%) of blood and
about 60m! of preservative.
The various preservatives are:
ACD (acid citrate dextrose)
+ Trisodium citrate = 2.2gm A
+ Citric acid = 0.8gmidl
+ Dextrose
+ Water upto = 100m!
+ pH =5.0-5.1
+ 67.5ml ACD is mixed with 420-450m! of blood duration of storage =
gm al
21 days
Preservatives:
+ Acid citrate dextrose (ACD) -21 days
+ Citrate phosphate dextrose (CPD) -28 days
+ CPD + adenine - 35 days
Blood & Blood Products.Continuation:
CPD (citrate phosphate dextrose)
+ Trisodium citrate - 2.6gm /dl
+ Citric acid - 0.327gmail
+ Sodium dihydrogen phosphate - 0.2gm /dl
+ Dextrose - 2.55gm dl
+ Water - 100 mi
pH -55
+ 63ml of CPD with 450m! of whole blood storage duration - 28
days
1. Citrate prevents clotting by binding calcium.
2. Dextrose allows continuation of glycolysis of RBC and thus
maintains sufficient concentrations of high energy ATP to
ensure continued red blood cell metabolism and subsequence
Viability during storage.
3. The acid of CPD (pH = 5.5) acts as a buffer and counter acts
the large fall in hydrogen ions that occur when the blood is
cooled.
Other preservatives
3. CPD with adenine:
+ The addition of small amounts of adenine (0.25-0.5mg)
increases red blood cell survival of aiding synthesis, of ATP by
the RBCs to 35 days,
4. ADSOL (AS-1) - 49 days
+ Adenine — glucose — mannitol — sodium chloride is a preservative
for the storage of packed red blood cells, Storage time - 49
days.
5, Nutricel (AS-3)
+ Nutricel contains glucose; adenine; citrate; phosphate and
sodium chloride. With the addition of nutricel; the shelf life can be
extended to 42 days. Saline = 140mmolA; adenine = 1.5mmolA’
glucose = 50mmolA; mannitol = 30mmolA.
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
6) Frozen storage:
+ RBCs previously frozen to -790C in glycerol can be thawed without
damage; but it must be free from glycerol before being transfused.
Storage time-- several years.
The advantages of frozen and thawed RBCs are the following:
1. Blood of rare types can be stored for long periods, increasing
viability and eliminating outdating.
2. Frozen, reconstituted blood is believed to be safer in patients who
are especially susceptible to allergic reaction because the freezing
and washing process reduces sites with histocompatible antigens.
3. Frozen blood, low in fibrin and leukocyte aggregates, would be
safer in patients requiring massive blood transfusion.
4, Frozen washed blood may reduce risk of transfusion hepatitis.
5. Frozen RBCs may be desirable in clinical conditions requiring
prompt tissue oxygenation because normal levels of 2, 3-DPG are
retained in frozen erythrocytes.
Heparin:
+ Whole blood stored in heparin is used in some situations for priming
the pump during cardiopulmonary bypass.
+ Heparinized whole blood is used in open heart surgery to prevent
cardiac abnormalities that might result from depression of ionized
calcium levels by the citrate in other storage solutions.
+ Heparin anticoagulant is not a REC preservative because it lacks
glucose.
- Its anticoagulant effect is also neutralized during storage by the
thromboplastic substances liberated by the cellular elements of blood
during storage.
+ Blood stored in heparin must be used within 24 to 48 hours of
collection.
CPD (citrate phosphate dextrose)
+ Trisodium citrate - 2.6gm /dl
+ Citric acid - 0.327gmail
+ Sodium dihydrogen phosphate - 0.2gm /dl
+ Dextrose - 2.55gm dl
+ Water - 100 mi
pH -55
+ 63ml of CPD with 450m! of whole blood storage duration - 28
days
1. Citrate prevents clotting by binding calcium.
2. Dextrose allows continuation of glycolysis of RBC and thus
maintains sufficient concentrations of high energy ATP to
ensure continued red blood cell metabolism and subsequence
Viability during storage.
3. The acid of CPD (pH = 5.5) acts as a buffer and counter acts
the large fall in hydrogen ions that occur when the blood is
cooled.
Other preservatives
3. CPD with adenine:
+ The addition of small amounts of adenine (0.25-0.5mg)
increases red blood cell survival of aiding synthesis, of ATP by
the RBCs to 35 days,
4. ADSOL (AS-1) - 49 days
+ Adenine — glucose — mannitol — sodium chloride is a preservative
for the storage of packed red blood cells, Storage time - 49
days.
5, Nutricel (AS-3)
+ Nutricel contains glucose; adenine; citrate; phosphate and
sodium chloride. With the addition of nutricel; the shelf life can be
extended to 42 days. Saline = 140mmolA; adenine = 1.5mmolA’
glucose = 50mmolA; mannitol = 30mmolA.
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
6) Frozen storage:
+ RBCs previously frozen to -790C in glycerol can be thawed without
damage; but it must be free from glycerol before being transfused.
Storage time-- several years.
The advantages of frozen and thawed RBCs are the following:
1. Blood of rare types can be stored for long periods, increasing
viability and eliminating outdating.
2. Frozen, reconstituted blood is believed to be safer in patients who
are especially susceptible to allergic reaction because the freezing
and washing process reduces sites with histocompatible antigens.
3. Frozen blood, low in fibrin and leukocyte aggregates, would be
safer in patients requiring massive blood transfusion.
4, Frozen washed blood may reduce risk of transfusion hepatitis.
5. Frozen RBCs may be desirable in clinical conditions requiring
prompt tissue oxygenation because normal levels of 2, 3-DPG are
retained in frozen erythrocytes.
Heparin:
+ Whole blood stored in heparin is used in some situations for priming
the pump during cardiopulmonary bypass.
+ Heparinized whole blood is used in open heart surgery to prevent
cardiac abnormalities that might result from depression of ionized
calcium levels by the citrate in other storage solutions.
+ Heparin anticoagulant is not a REC preservative because it lacks
glucose.
- Its anticoagulant effect is also neutralized during storage by the
thromboplastic substances liberated by the cellular elements of blood
during storage.
+ Blood stored in heparin must be used within 24 to 48 hours of
collection.
Blood & Blood Products.Continuation:
after transfusion (9%)
Parameter Day 1 [Day 7| Day 14 | Day 21 | Day 35
TPH 72 | 7 | 69 | 684 | 673
12,3DPG mm) | 48 [72 | 1 E <i
Y P50 (mmHg) 25 | 23 | 20 | 17
T K+ (mean) 4 [2.17 | 2
T Hb (mg/dl) in plasma| 1.7 | 78 | 13 | 19 | 46
T Blood PCOZ (mmHg)| 48 | 80 | 110 | 140
Y Platelets (9%) 7 | o | 0 o 0
Y Viable cells 24 hrs | 100 | 98 | 85 | 80
Parameters that decreases:
+ pH (7.2)
+ Pso (26)
+ 2,3 DPG (4.8)
+ Platelet cells % (10%)
+ Mable cells 24 hrs later % (100%)
Parameters that increases:
+ K (4)
+ PCO2
+ Hbin plasma
Blood transfusion:
+ Considerable morbidity and to a lesser extent mortality are
associated with blood transfusion therapy. Blood and blood
products should be transfused only when there are clear
therapeutic indications.
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
+ Changes that occur during storage of whole blood in CPD at 40C The recommendations of the ASA practice guidelines Include:
+ Transfusion is rarely indicated when the Hb concentration is greater
than 10gm/dl and is almost always indicated when it is less than
6gm/dl, especially when the anemia is acute.
- The determination of whether intermediate Hb comes (6 to 10gm/l)
justifies or require red blood cell transfusion should be based on the
patients risk for complications of inadequate oxygenation
+ The use of a single haemoglobin ‘trigger’ for all patients and other
approaches that fail to consider all important physiologic and surgical
factors affecting oxygenation are not recommended.
+ When appropriate, preoperative autologous blood donation,
intraoperative and postoperative blood recovery; acute normovolemic
hemodilution and measures to decrease blood loss may be
beneficial.
+ The indications for transfusion of autologous RBCs may be more
liberal than those for allogeneic RBCs because of lower risks
associated with the former.
Recommendations:
+ Hb > 10 not indicated, < 6gidl acute.
+ 6-10 g/dl > based on patients risk for complications of inadequate
‘oxygenation.
Administrations of one unit of packed RBCs will increase hematocrit
value by 3-5 percent. Indications are
Blood loss > 20 percent of blood volume
Haemoglobin < 8gmédl
Haemoglobin < 10gmdl with major d/s eg. emphysema; IHD
Haemoglobin 10gm/dl with autologous blood.
Haemoglobin < 12gmidl and ventilator dependence
nap
10
after transfusion (9%)
Parameter Day 1 [Day 7| Day 14 | Day 21 | Day 35
TPH 72 | 7 | 69 | 684 | 673
12,3DPG mm) | 48 [72 | 1 E <i
Y P50 (mmHg) 25 | 23 | 20 | 17
T K+ (mean) 4 [2.17 | 2
T Hb (mg/dl) in plasma| 1.7 | 78 | 13 | 19 | 46
T Blood PCOZ (mmHg)| 48 | 80 | 110 | 140
Y Platelets (9%) 7 | o | 0 o 0
Y Viable cells 24 hrs | 100 | 98 | 85 | 80
Parameters that decreases:
+ pH (7.2)
+ Pso (26)
+ 2,3 DPG (4.8)
+ Platelet cells % (10%)
+ Mable cells 24 hrs later % (100%)
Parameters that increases:
+ K (4)
+ PCO2
+ Hbin plasma
Blood transfusion:
+ Considerable morbidity and to a lesser extent mortality are
associated with blood transfusion therapy. Blood and blood
products should be transfused only when there are clear
therapeutic indications.
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
+ Changes that occur during storage of whole blood in CPD at 40C The recommendations of the ASA practice guidelines Include:
+ Transfusion is rarely indicated when the Hb concentration is greater
than 10gm/dl and is almost always indicated when it is less than
6gm/dl, especially when the anemia is acute.
- The determination of whether intermediate Hb comes (6 to 10gm/l)
justifies or require red blood cell transfusion should be based on the
patients risk for complications of inadequate oxygenation
+ The use of a single haemoglobin ‘trigger’ for all patients and other
approaches that fail to consider all important physiologic and surgical
factors affecting oxygenation are not recommended.
+ When appropriate, preoperative autologous blood donation,
intraoperative and postoperative blood recovery; acute normovolemic
hemodilution and measures to decrease blood loss may be
beneficial.
+ The indications for transfusion of autologous RBCs may be more
liberal than those for allogeneic RBCs because of lower risks
associated with the former.
Recommendations:
+ Hb > 10 not indicated, < 6gidl acute.
+ 6-10 g/dl > based on patients risk for complications of inadequate
‘oxygenation.
Administrations of one unit of packed RBCs will increase hematocrit
value by 3-5 percent. Indications are
Blood loss > 20 percent of blood volume
Haemoglobin < 8gmédl
Haemoglobin < 10gmdl with major d/s eg. emphysema; IHD
Haemoglobin 10gm/dl with autologous blood.
Haemoglobin < 12gmidl and ventilator dependence
nap
10
Blood & Blood Products.Continuation:
COMPATIBILITY TESTING:
+ Compatibility testing are designed to demonstrate harmful
antigen, antibody interactions in vitro so that harmful in vivo
antigen-antibody interactions could be prevented.
+ The ABO-Rh type, cross match and antibody screen are
frequently referred to as compatibility tests.
1. ABO-Rh typing:
+ Determination of ABO group and Rh of the recipient and donor is
the Ist step in selecting blood for transfusion therapy. ABO
typing is performed by testing RBCs for the A and B antigens and
the serum for the A and B antibodies before transfusion. The only
additional required testing is that for the Ah (D) ag. About 85% of
individuals possess the D antigen and are termed Rh(D) positive,
the remaining 15 percent, who lack the D antigen, are termed Rh
(D) negative.
11. Cross matching:
+ Across match is essentially a “trial transfusion’ within a test tube
in which donor RBCs are mixed with recipient serum to detect a
potential for series transfusion reactions. The cross match can
be completed in 45 to 60 mins and is done in three phases: an
immediate phase; an incubation phase; and an anti-globulin
phase.
a) Immediate phase:
+ The immediate phase is conducted at room temperature. It
detects ABO incompatibilities and those caused by naturally
occurring antibodies in the MN, P and Lewis systems. This takes
approx. 1 to 5 mins to complete.
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
b) Incubation phase:
+ Involves incubation of the 1% phase reaction at 37°C in albumin or
low ionic strength salt solution. The addition of these 2 aids in the
detection of incomplete antibodies or those antibodies that are able
to attach to a specific antigen (sensitization) but unable to cause
agglutination in a saline suspension of red blood cells.
+ This phase primarily detects antibodies in the Rh system. The
incubation of 30 to 45 mins in albumin and of 10-20 mins in low ionic
strength salt solution in this phase is of sufficient duration to allow
antibody uptake sensitization by the cells so that incomplete
antibodies missed in this phase can be detected in the subsequent
anti-globulin phase.
€) Anti-globulin phase:
+ Involves the addition of anti-globulin sera to the incubated test tubes
with this addition, antihuman antibodies present in the sera become
attached to the antibody globulin on the red blood cells, thus causing
agglutination. This phase detects most incomplete antibodies in the
blood group systems including the Rh, Kell, Kidd and Duffy blood
group systems.
‘Types of cross match:
Major cross match: is done when the donor's erythrocytes are
incubated with the plasma of the recipient. Agglutination confirms that
the plasma of the recipient contains antibodies to antigens on cell
membranes of donor erythrocytes.
Minor cross match: is done when the plasma of the donor is incubated
with the erythrocytes of the recipient. Agglutination results if the
plasma of the donor contains antibodies to antigens on cell
membranes of recipient erythrocytes.
Ill. Antibody screening:
+ This is also carried out in 3 phases and is similar in length to the
cross match. This test is conducted on recipient serum to rule out the
possibility of hemolytic transfusion reaction. It is also done on the
donor serum to detect unexpected antibodies in order to prevent their
introduction into the recipients serum or to prevent reactions between
transfused donor units.
"
COMPATIBILITY TESTING:
+ Compatibility testing are designed to demonstrate harmful
antigen, antibody interactions in vitro so that harmful in vivo
antigen-antibody interactions could be prevented.
+ The ABO-Rh type, cross match and antibody screen are
frequently referred to as compatibility tests.
1. ABO-Rh typing:
+ Determination of ABO group and Rh of the recipient and donor is
the Ist step in selecting blood for transfusion therapy. ABO
typing is performed by testing RBCs for the A and B antigens and
the serum for the A and B antibodies before transfusion. The only
additional required testing is that for the Ah (D) ag. About 85% of
individuals possess the D antigen and are termed Rh(D) positive,
the remaining 15 percent, who lack the D antigen, are termed Rh
(D) negative.
11. Cross matching:
+ Across match is essentially a “trial transfusion’ within a test tube
in which donor RBCs are mixed with recipient serum to detect a
potential for series transfusion reactions. The cross match can
be completed in 45 to 60 mins and is done in three phases: an
immediate phase; an incubation phase; and an anti-globulin
phase.
a) Immediate phase:
+ The immediate phase is conducted at room temperature. It
detects ABO incompatibilities and those caused by naturally
occurring antibodies in the MN, P and Lewis systems. This takes
approx. 1 to 5 mins to complete.
Dr Azam's Notes in Anesthesiology 2013
Dr Azants Notes in Anesthesiology 2013
b) Incubation phase:
+ Involves incubation of the 1% phase reaction at 37°C in albumin or
low ionic strength salt solution. The addition of these 2 aids in the
detection of incomplete antibodies or those antibodies that are able
to attach to a specific antigen (sensitization) but unable to cause
agglutination in a saline suspension of red blood cells.
+ This phase primarily detects antibodies in the Rh system. The
incubation of 30 to 45 mins in albumin and of 10-20 mins in low ionic
strength salt solution in this phase is of sufficient duration to allow
antibody uptake sensitization by the cells so that incomplete
antibodies missed in this phase can be detected in the subsequent
anti-globulin phase.
€) Anti-globulin phase:
+ Involves the addition of anti-globulin sera to the incubated test tubes
with this addition, antihuman antibodies present in the sera become
attached to the antibody globulin on the red blood cells, thus causing
agglutination. This phase detects most incomplete antibodies in the
blood group systems including the Rh, Kell, Kidd and Duffy blood
group systems.
‘Types of cross match:
Major cross match: is done when the donor's erythrocytes are
incubated with the plasma of the recipient. Agglutination confirms that
the plasma of the recipient contains antibodies to antigens on cell
membranes of donor erythrocytes.
Minor cross match: is done when the plasma of the donor is incubated
with the erythrocytes of the recipient. Agglutination results if the
plasma of the donor contains antibodies to antigens on cell
membranes of recipient erythrocytes.
Ill. Antibody screening:
+ This is also carried out in 3 phases and is similar in length to the
cross match. This test is conducted on recipient serum to rule out the
possibility of hemolytic transfusion reaction. It is also done on the
donor serum to detect unexpected antibodies in order to prevent their
introduction into the recipients serum or to prevent reactions between
transfused donor units.
"
2. Development of Red Blood Cells.
Precursor stage Hans
Progenitor cells Tiymphocytes
of the immune ‘Non-8, non-T
system Iymphocytes
.B. Lymphocytes,
plasma cells
SELF REPLICATING
TOTIPOTENT STEM
‘CELLS
Erythroid series erythrocytes
Megakaryocyte - platelets
Monocytes ~ macrophages series —
= < ‘monocytes and macrophages
Neutrophils series - segmented
Neutrophils
Eosinophil series ~ segmented
Eosinophils
Basophil series - segmented
Basophils
“Romanovsky stains
Dr Azam's Notes in Anesthesiology 2013
Granulocytes
Dr Azam's Notes in Anesthesiology 2013
DEVELOPMENT OF BLOOD CELLS:
+ Blood cells develop from a small population of
TOTIPOTENT hematopoietic STEM CELLS which maintain
their numbers by self replication and also gives rise to
Precursors of one or other of the various blood cells series
and cells of the immune system
Bombay Blood group:
+ Extremely rare ABO group
+ First discovered in Bombay
+ Their red cell lack ABH antigen and their sera
containing Anti - A, Anti - B and Anti H.
+ The Anti H would not be detected in ABO group.
Other Systems other than AB
+ M&N system
+ Kell System
+ Lewis system
+ Kidd - Zolinger
+ Duffy
+ 1=1 &i antigen
+ P- similar to ABO
+ Lutheran
12
Precursor stage Hans
Progenitor cells Tiymphocytes
of the immune ‘Non-8, non-T
system Iymphocytes
.B. Lymphocytes,
plasma cells
SELF REPLICATING
TOTIPOTENT STEM
‘CELLS
Erythroid series erythrocytes
Megakaryocyte - platelets
Monocytes ~ macrophages series —
= < ‘monocytes and macrophages
Neutrophils series - segmented
Neutrophils
Eosinophil series ~ segmented
Eosinophils
Basophil series - segmented
Basophils
“Romanovsky stains
Dr Azam's Notes in Anesthesiology 2013
Granulocytes
Dr Azam's Notes in Anesthesiology 2013
DEVELOPMENT OF BLOOD CELLS:
+ Blood cells develop from a small population of
TOTIPOTENT hematopoietic STEM CELLS which maintain
their numbers by self replication and also gives rise to
Precursors of one or other of the various blood cells series
and cells of the immune system
Bombay Blood group:
+ Extremely rare ABO group
+ First discovered in Bombay
+ Their red cell lack ABH antigen and their sera
containing Anti - A, Anti - B and Anti H.
+ The Anti H would not be detected in ABO group.
Other Systems other than AB
+ M&N system
+ Kell System
+ Lewis system
+ Kidd - Zolinger
+ Duffy
+ 1=1 &i antigen
+ P- similar to ABO
+ Lutheran
12
3. Blood Group system.
There are two Systems: ABO & Rh.
1) ABO system:
+ Aand B antigens are inherited as Mendelian
dominants, and individuals are divided into 4 major
blood types on this basis.
+ Type A individuals have A ag on the RBCs
- Type B individuals have B ag
- Type AB individuals have both antigens
+ Type O individuals have neither
+ Several subgroups of A exist; the most important
being Ay and Az.
+ The difference between A: and A» appears to be
quantitative, Each A; cell has about 1,000,000
copies of the A ag on its surface and each Az cell
has about 250,000.
+ The A and B antigens are found in many tissues in
addition to blood these include salivary glands,
saliva, pancreas, kidney, liver, lungs, testes, semen
and amniotic fluid,
+ Antibodies against red cell agglutinogen are called
agglutinins.
+ The serum of an individual contains antibodies
against the Ags lacking on the persons red cells.
Thus type A individuals develop anti B antibodies;
type B individuals develop anti A abs, type O
individuals develop both, type AB individuals
develop neither.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
2) The Rh group:
+ The Rhesus (Rh) blood group system was first demonstrated in
humans, by the use of an antiserum prepared by immunizing
rabbits with red cells from a thesus monkey. It was found that
some human red cells were agglutinated by the serum “Rh +ve
cells” - while others were not - “Ah -ve cells’. This system is
composed primarily of C, D and E antigens of which D is the
most important antigenic component and the term “Rh positive”
means that the individual has the D antigen and “th -ve’ means
that the individual has no D antigen
+ Over 99% of Asians are D +ve. Unlike the antibodies of the ABO
system anti-D abs do not develop without exposure of a D -ve
individual to D +ve red cells by transfusion or entrance of fetal
blood into the maternal circulation.
Bombay Blood group:
+ Thisis an extremely rare ABO group, called so because it was
first discovered among some people in Bombay (now Mumbai)
Although the group is more likely to occur in East Indians, it is a
very rare group even here.
+ Itis not restricted to East Indians but found in Caucasians,
Japanese, etc.
+ Their red cells lack ABH antigens and their sera contain anti-A
and anti-B and anti-H
+ The anti-H would not be detected in the ABO group but would be
detectable in pre-transfusion tests.
13
There are two Systems: ABO & Rh.
1) ABO system:
+ Aand B antigens are inherited as Mendelian
dominants, and individuals are divided into 4 major
blood types on this basis.
+ Type A individuals have A ag on the RBCs
- Type B individuals have B ag
- Type AB individuals have both antigens
+ Type O individuals have neither
+ Several subgroups of A exist; the most important
being Ay and Az.
+ The difference between A: and A» appears to be
quantitative, Each A; cell has about 1,000,000
copies of the A ag on its surface and each Az cell
has about 250,000.
+ The A and B antigens are found in many tissues in
addition to blood these include salivary glands,
saliva, pancreas, kidney, liver, lungs, testes, semen
and amniotic fluid,
+ Antibodies against red cell agglutinogen are called
agglutinins.
+ The serum of an individual contains antibodies
against the Ags lacking on the persons red cells.
Thus type A individuals develop anti B antibodies;
type B individuals develop anti A abs, type O
individuals develop both, type AB individuals
develop neither.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
2) The Rh group:
+ The Rhesus (Rh) blood group system was first demonstrated in
humans, by the use of an antiserum prepared by immunizing
rabbits with red cells from a thesus monkey. It was found that
some human red cells were agglutinated by the serum “Rh +ve
cells” - while others were not - “Ah -ve cells’. This system is
composed primarily of C, D and E antigens of which D is the
most important antigenic component and the term “Rh positive”
means that the individual has the D antigen and “th -ve’ means
that the individual has no D antigen
+ Over 99% of Asians are D +ve. Unlike the antibodies of the ABO
system anti-D abs do not develop without exposure of a D -ve
individual to D +ve red cells by transfusion or entrance of fetal
blood into the maternal circulation.
Bombay Blood group:
+ Thisis an extremely rare ABO group, called so because it was
first discovered among some people in Bombay (now Mumbai)
Although the group is more likely to occur in East Indians, it is a
very rare group even here.
+ Itis not restricted to East Indians but found in Caucasians,
Japanese, etc.
+ Their red cells lack ABH antigens and their sera contain anti-A
and anti-B and anti-H
+ The anti-H would not be detected in the ABO group but would be
detectable in pre-transfusion tests.
13
4. Blood storage System.
1. Several different preservative solutions can
be added to either whole blood or packed
RBCs to allow storage of these products.
2. In general preservative solutions contain
additives that
a. Prevent coagulation
b. Support glycolysis
c. Maintain ATP generation
3. The preservative determines the blood
products storage on shelf life, The duration of
storage is determined by the requirement
that at least 70% of the transfused red blood
cells remain in circulation for 24 hrs after
infusion.
4. Aunit of whole blood generally contains
450ml (+ 10%) of blood and about 60m! of
preservative.
The various preservatives ar
ACD (acid citrate dextrose) - 21 days.
+ Trisodium citrate = 2.2gm Ail
+ Citric acid = 0, 8grrval
+ Dextrose = 2.5gm /dl
+ Water upto = 100m!
+ pH =5.05.1
+ 67.5ml ACD is mixed with 420-450m of blood
duration of storage = 21 days
Preservatives:
+ Acid citrate dextrose (ACD) -21 days
+ Citrate phosphate dextrose (CPD) -28 days
+ CPD + adenine - 35 days
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
CPD (citrate phosphate dextrose): - 28 days
Trisodium citrate - 2.6gm dl
Citric acid -0.327gmvdl
Sodium di hydrogen phosphate - 0.2gm /dl
Dextrose - 2.559m al
Water - 100 mi
pH -55
+ 63ml of CPD with 450m! of whole blood storage duration — 28 days
1. Citrate prevents clotting by binding calcium.
2. Dextrose allows continuation of glycolysis of RBC and thus maintains
sufficient concentrations of high energy ATP to ensure continued red
blood cell metabolism and subsequence viability during storage.
3. The acid of CPD (pH = 5.5) acts as a buffer and counter acts the large
fall in hydrogen ions that occur when the blood is cooled,
Other preservatives
CPD with adenine: - 35 days
+ The addition of small amounts of adenine (0.25-0.5mg) increases red
blood cell survival of aiding synthesis, of ATP by the RBCs to 35 days.
ADSOL (AS-1) - 49 days
+ Adenine - glucose - mannitol — sodium chloride is a preservative for the
storage of packed red blood cells. Storage time - 49 days.
Nutricel (AS-3): 42 days
+ Nutricel contains glucose; adenine; citrate; phosphate and sodium
chloride. With the addition of nutricel; the shelf life can be extended to 42
days. Saline = 140mmolA; adenine = 1.5mmolf' glucose = 50mmolA;
mannitol = 30mmolA.
Frozen storage: 3 to 5 years
+ RBCs previously frozen to -79°C in glycerol can be thawed without
damage; but it must be free from glycerol before being transfused.
Storage time - several years.
14
1. Several different preservative solutions can
be added to either whole blood or packed
RBCs to allow storage of these products.
2. In general preservative solutions contain
additives that
a. Prevent coagulation
b. Support glycolysis
c. Maintain ATP generation
3. The preservative determines the blood
products storage on shelf life, The duration of
storage is determined by the requirement
that at least 70% of the transfused red blood
cells remain in circulation for 24 hrs after
infusion.
4. Aunit of whole blood generally contains
450ml (+ 10%) of blood and about 60m! of
preservative.
The various preservatives ar
ACD (acid citrate dextrose) - 21 days.
+ Trisodium citrate = 2.2gm Ail
+ Citric acid = 0, 8grrval
+ Dextrose = 2.5gm /dl
+ Water upto = 100m!
+ pH =5.05.1
+ 67.5ml ACD is mixed with 420-450m of blood
duration of storage = 21 days
Preservatives:
+ Acid citrate dextrose (ACD) -21 days
+ Citrate phosphate dextrose (CPD) -28 days
+ CPD + adenine - 35 days
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
CPD (citrate phosphate dextrose): - 28 days
Trisodium citrate - 2.6gm dl
Citric acid -0.327gmvdl
Sodium di hydrogen phosphate - 0.2gm /dl
Dextrose - 2.559m al
Water - 100 mi
pH -55
+ 63ml of CPD with 450m! of whole blood storage duration — 28 days
1. Citrate prevents clotting by binding calcium.
2. Dextrose allows continuation of glycolysis of RBC and thus maintains
sufficient concentrations of high energy ATP to ensure continued red
blood cell metabolism and subsequence viability during storage.
3. The acid of CPD (pH = 5.5) acts as a buffer and counter acts the large
fall in hydrogen ions that occur when the blood is cooled,
Other preservatives
CPD with adenine: - 35 days
+ The addition of small amounts of adenine (0.25-0.5mg) increases red
blood cell survival of aiding synthesis, of ATP by the RBCs to 35 days.
ADSOL (AS-1) - 49 days
+ Adenine - glucose - mannitol — sodium chloride is a preservative for the
storage of packed red blood cells. Storage time - 49 days.
Nutricel (AS-3): 42 days
+ Nutricel contains glucose; adenine; citrate; phosphate and sodium
chloride. With the addition of nutricel; the shelf life can be extended to 42
days. Saline = 140mmolA; adenine = 1.5mmolf' glucose = 50mmolA;
mannitol = 30mmolA.
Frozen storage: 3 to 5 years
+ RBCs previously frozen to -79°C in glycerol can be thawed without
damage; but it must be free from glycerol before being transfused.
Storage time - several years.
14
[Blood storage System.Continued Dr Azam's Notes in Anesthesiology 2013
The advantages of frozen and thawed RBCs are the following: Changes that occur during storage of whole blood in CPD at 40°C
1. Blood of rare types can be stored for long periods, Parameter Dayi [Pay7 Day14 Day2i Pays
increasing viability and eliminating outdating.
2. Frozen, reconstituted blood is believed to be safer in (LT) PH E TP #4 Fa
patients who are especially susceptible to allergic reaction 4 2) 23 DPG (umiml) 14.8 7.2 F1
because the freezing and washing process reduces sites 1 3) P50 (mmHg) bes po 7
with histocompatible antigens. pn ha h7 Tk
3. Frozen blood, low in fibrin and leukocyte aggregates, ee) 5 5 5
would be safer in patients requiring massive blood [t_ 5) Hb (mg/dl) in plasmalt i pl
transfusion It 6) Blood PCO2 US Bo [mo 140
4. Frozen washed blood may reduce risk of transfusion (mmHg)
8 ON . aa IL 7) Platelets (9%) 10
rozen RBCs may be desirable in clinical conditions 1.8) Viable cells 24hrs 100 BS o
requiring prompt tissue oxygenation because normal levels biter transfusion (4) i
of 2, 3-DPG are retained in frozen erythrocytes.
Heparin:
+ Whole blood stored in heparin is used in some situations for pH (7.2) K (4)
priming the pump during cardiopulmonary bypass. Pso (26) PCO,
+ Heparinized whole blood is used in open heart surgery to 2,3 DPG (4.8) Hb in plasma
prevent cardiac abnormalities that might result from Platelet cells % (10%)
depression of ionized calcium levels by the citrate in other Viable cells 24 hrs later
storage solutions. 6 (100%)
+ Heparin anticoagulant is not a RBC preservative because it
lacks glucose. Its anticoagulant effect is also neutralized
during storage by the thromboplastic substances liberated
by the cellular elements of blood during storage.
+ Blood stored in heparin must be used within 24 to 48 hours
of collection.
15
Dr Azam's Notes in Anesthesiology 2013
The advantages of frozen and thawed RBCs are the following: Changes that occur during storage of whole blood in CPD at 40°C
1. Blood of rare types can be stored for long periods, Parameter Dayi [Pay7 Day14 Day2i Pays
increasing viability and eliminating outdating.
2. Frozen, reconstituted blood is believed to be safer in (LT) PH E TP #4 Fa
patients who are especially susceptible to allergic reaction 4 2) 23 DPG (umiml) 14.8 7.2 F1
because the freezing and washing process reduces sites 1 3) P50 (mmHg) bes po 7
with histocompatible antigens. pn ha h7 Tk
3. Frozen blood, low in fibrin and leukocyte aggregates, ee) 5 5 5
would be safer in patients requiring massive blood [t_ 5) Hb (mg/dl) in plasmalt i pl
transfusion It 6) Blood PCO2 US Bo [mo 140
4. Frozen washed blood may reduce risk of transfusion (mmHg)
8 ON . aa IL 7) Platelets (9%) 10
rozen RBCs may be desirable in clinical conditions 1.8) Viable cells 24hrs 100 BS o
requiring prompt tissue oxygenation because normal levels biter transfusion (4) i
of 2, 3-DPG are retained in frozen erythrocytes.
Heparin:
+ Whole blood stored in heparin is used in some situations for pH (7.2) K (4)
priming the pump during cardiopulmonary bypass. Pso (26) PCO,
+ Heparinized whole blood is used in open heart surgery to 2,3 DPG (4.8) Hb in plasma
prevent cardiac abnormalities that might result from Platelet cells % (10%)
depression of ionized calcium levels by the citrate in other Viable cells 24 hrs later
storage solutions. 6 (100%)
+ Heparin anticoagulant is not a RBC preservative because it
lacks glucose. Its anticoagulant effect is also neutralized
during storage by the thromboplastic substances liberated
by the cellular elements of blood during storage.
+ Blood stored in heparin must be used within 24 to 48 hours
of collection.
15
Dr Azam's Notes in Anesthesiology 2013
5. Recommendation of Blood transfusion.
BLOOD TRANSFUSION:
+ Considerable morbidity and to a lesser extent mortality
are associated with blood transfusion therapy. Blood and
blood products should be transfused only when there are
clear therapeutic indications.
‘The recommendations of the ASA practice guidelines
include:
|. Transfusion is rarely indicated when the Hb
concentration is greater than 10gm/di and is almost
always indicated when it is less than 6gm/dl, especially
when the anemia is acute
Il. The determination of whether intermediate Hb
(6 to 10gmidl) justifies or require red blood cell
transfusion should be based on the patients risk for
complications of inadequate oxygenation.
111. The use of a single haemoglobin “trigger for all
patients and other approaches that fail to consider all
important physiologic and surgical factors affecting
oxygenation are not recommended
IV. When appropriate, preoperative autologous blood
donation, intraoperative and postoperative blood
salvage; acute normovolaemic hemodilution and
measures to decrease blood loss may be beneficial
V. The indications for transfusion of autologous RBCs
may be more liberal than those for allogeneic RECs
because of lower risks associated with the former.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Recommendations:
1. Hb > 10 not indicated, < 6g/dl acute - Always Indicated.
2. 6-10 gidl > based on patients risk for complications of
inadequate oxygenation.
+ Administrations of one unit of packed RBCs will increase
hematocrit value by 3-5 percent. Indications are
|. Blood loss > 20 percent of blood volume
Il. Haemoglobin < &gm/al
111. Haemoglobin < 10gmédl with major dís e.g. emphysema; IHD
IV. Haemoglobin 10gmadl with autologous blood.
V. Haemoglobin < T2gm4l and ventilator dependence
16
BLOOD TRANSFUSION:
+ Considerable morbidity and to a lesser extent mortality
are associated with blood transfusion therapy. Blood and
blood products should be transfused only when there are
clear therapeutic indications.
‘The recommendations of the ASA practice guidelines
include:
|. Transfusion is rarely indicated when the Hb
concentration is greater than 10gm/di and is almost
always indicated when it is less than 6gm/dl, especially
when the anemia is acute
Il. The determination of whether intermediate Hb
(6 to 10gmidl) justifies or require red blood cell
transfusion should be based on the patients risk for
complications of inadequate oxygenation.
111. The use of a single haemoglobin “trigger for all
patients and other approaches that fail to consider all
important physiologic and surgical factors affecting
oxygenation are not recommended
IV. When appropriate, preoperative autologous blood
donation, intraoperative and postoperative blood
salvage; acute normovolaemic hemodilution and
measures to decrease blood loss may be beneficial
V. The indications for transfusion of autologous RBCs
may be more liberal than those for allogeneic RECs
because of lower risks associated with the former.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Recommendations:
1. Hb > 10 not indicated, < 6g/dl acute - Always Indicated.
2. 6-10 gidl > based on patients risk for complications of
inadequate oxygenation.
+ Administrations of one unit of packed RBCs will increase
hematocrit value by 3-5 percent. Indications are
|. Blood loss > 20 percent of blood volume
Il. Haemoglobin < &gm/al
111. Haemoglobin < 10gmédl with major dís e.g. emphysema; IHD
IV. Haemoglobin 10gmadl with autologous blood.
V. Haemoglobin < T2gm4l and ventilator dependence
16
6. Compatibility Testing
+ Compatibility testing are designed to demonstrate harmful
antigen, antibody interactions in vitro so that harmful in vivo
antigen-antibody interactions could be prevented
+ The ABO-Rh type, cross match and antibody screen are
frequently referred to as compatibility tests.
1. ABO-Rh typing:
+ Determination of ABO group and Rh of the recipient and
donor is the 1 step in selecting blood for transfusion
therapy. ABO typing is performed by testing RBCs for the A
and B antigens and the serum for the A and B antibodies
before transfusion. The only additional required testing is that
for the Rh (D) ag. About 85% of individuals possess the D
antigen and are termed Ah(D) positive, the remaining 15
percent, who lack the D antigen, are termed Rh(D) negative.
11. Cross matching:
+ Across match is essentially a ‘trial transfusion” within a test
tube in which donor RBCs are mixed with recipient serum to
detect a potential for series transfusion reactions. The cross
match can be completed in 45 to 60 mins and is done in
three phases: an immediate phase; an incubation phase; and
an antiglobulin phase,
a) Immediate phase:
+ The immediate phase is conducted at room temperature, It
detects ABO incompatibilities and those caused by naturally
‘occurring antibodies in the MN, P and Lewis systems. This
takes approx. 1 to 5 mins to complete.
b) Incubation phase:
+ Involves incubation of the 1st phase reaction at 37 °C in
albumin or low ionic strength salt solution. The addition of
these 2 aids in the detection of incomplete antibodies or
those antibodies that are able to attach to a specific antigen
(sensitization) but unable to cause agglutination in a saline
suspension of red blood cells.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ This phase primarily detects antibodies in the Rh system. The
incubation of 30 to 45 mins in albumin and of 10-20 mins in low ionic
strength salt solution in this phase is of sufficient duration to allow
antibody uptake sensitization by the cells so that incomplete antibodies
missed in this phase can be detected in the subsequent antiglobulin
phase.
©) Antiglobulin phase:
+ Involves the addition of antiglobulin sera to the incubated test tubes
with this addition, antinuman antibodies present in the sera become
attached to the antibody globulin on the red blood cells, thus causing
agglutination. This phase detects most incomplete antibodies in the
blood group systems including the Rh, Kell, Kidd and Duffy blood group
systems.
Types of cross mate
+ Major cross match: is done when the donor's erythrocytes are
incubated with the plasma of the recipient. Agglutination confirms that
the plasma of the recipient contains antibodies to antigens on cell
membranes of donor erythrocytes.
+ Minor cross match: is done when the plasma of the donor is incubated
with the erythrocytes of the recipient. Agglutination results if the plasma
of the donor contains antibodies to antigens on cell membranes of
recipient erythrocytes.
|. Antibody screening:
This is also carried out in 3 phases and is similar in length to the cross
match. This test is conducted on recipient serum to rule out the
Possibility of hemolytic transfusion reaction. It is also done on the donor
serum to detect unexpected antibodies in order to prevent their
introduction into the recipients serum or to prevent reactions between
transfused donor units.
17
+ Compatibility testing are designed to demonstrate harmful
antigen, antibody interactions in vitro so that harmful in vivo
antigen-antibody interactions could be prevented
+ The ABO-Rh type, cross match and antibody screen are
frequently referred to as compatibility tests.
1. ABO-Rh typing:
+ Determination of ABO group and Rh of the recipient and
donor is the 1 step in selecting blood for transfusion
therapy. ABO typing is performed by testing RBCs for the A
and B antigens and the serum for the A and B antibodies
before transfusion. The only additional required testing is that
for the Rh (D) ag. About 85% of individuals possess the D
antigen and are termed Ah(D) positive, the remaining 15
percent, who lack the D antigen, are termed Rh(D) negative.
11. Cross matching:
+ Across match is essentially a ‘trial transfusion” within a test
tube in which donor RBCs are mixed with recipient serum to
detect a potential for series transfusion reactions. The cross
match can be completed in 45 to 60 mins and is done in
three phases: an immediate phase; an incubation phase; and
an antiglobulin phase,
a) Immediate phase:
+ The immediate phase is conducted at room temperature, It
detects ABO incompatibilities and those caused by naturally
‘occurring antibodies in the MN, P and Lewis systems. This
takes approx. 1 to 5 mins to complete.
b) Incubation phase:
+ Involves incubation of the 1st phase reaction at 37 °C in
albumin or low ionic strength salt solution. The addition of
these 2 aids in the detection of incomplete antibodies or
those antibodies that are able to attach to a specific antigen
(sensitization) but unable to cause agglutination in a saline
suspension of red blood cells.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ This phase primarily detects antibodies in the Rh system. The
incubation of 30 to 45 mins in albumin and of 10-20 mins in low ionic
strength salt solution in this phase is of sufficient duration to allow
antibody uptake sensitization by the cells so that incomplete antibodies
missed in this phase can be detected in the subsequent antiglobulin
phase.
©) Antiglobulin phase:
+ Involves the addition of antiglobulin sera to the incubated test tubes
with this addition, antinuman antibodies present in the sera become
attached to the antibody globulin on the red blood cells, thus causing
agglutination. This phase detects most incomplete antibodies in the
blood group systems including the Rh, Kell, Kidd and Duffy blood group
systems.
Types of cross mate
+ Major cross match: is done when the donor's erythrocytes are
incubated with the plasma of the recipient. Agglutination confirms that
the plasma of the recipient contains antibodies to antigens on cell
membranes of donor erythrocytes.
+ Minor cross match: is done when the plasma of the donor is incubated
with the erythrocytes of the recipient. Agglutination results if the plasma
of the donor contains antibodies to antigens on cell membranes of
recipient erythrocytes.
|. Antibody screening:
This is also carried out in 3 phases and is similar in length to the cross
match. This test is conducted on recipient serum to rule out the
Possibility of hemolytic transfusion reaction. It is also done on the donor
serum to detect unexpected antibodies in order to prevent their
introduction into the recipients serum or to prevent reactions between
transfused donor units.
17
7. Blood Component therapy & Blood substitutes
+ Except for conditions which result in acute haemorrhage,
transfusion therapy is occasioned by the need to correct or
deficiency in a specific component of whole blood. The
rationale for component therapy stems from the recognition
that blood is a complex tissue with numerous constituents or
components, both cellular and noncellular, serving disease
functions. Component therapy permits the physician to
deliver an effective, therapeutic dose of the deficient
component with minimum risk of circulatory overload, or of
adverse reactions to the administration of unnecessary blood
components.
Blood components:
1. Erythrocyte preparations:
1. Packed red cells
2, Leucocyte poor red cell
3, Washed red cells
4, Frozen red cells
Il. Leukocytes:
1. Granulooytes
2, Mononuclear cells
Ill, Platelets
IV. Plasma fractions:
Fresh frozen plasma
2. Platelet rich plasma
3. Cryoprecipitate
4, Fractionated plasma
o Factor VIII concentrate
© Prothrombin complex concentration and factor IX
concentrate
o Albumin
© Immunoglobulin
© Antithrombin Ill concentrates
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Diagrammatic scheme of how whole blood is separated for component
therapy:
Whole |centituse [platelet Platelet | Freeze „[ Factor vit
blood rich plasma [ve "| poor plasma | 77e >| poor plasma
Free | row
200
y
Packed red Platelets Ciyoprecipitate
cell Fresh
free frozen La
bo plasma | thawing
| frozenred | [Leucocyte
cells poor red cells
|. Erythrocyte preparations:
1) Packed red blood cells:
+ The red cells from whole blood can be administered after removing
80% of the plasma, Packed red cells have a hematocrit of 60-90%.
+ RBCs, rather than whole blood, should be used for the treatment of all
patients who require a transfusion because of a red cell mass deficit
An absolute requirement for RBC exists, when transfusing anemic
patients with actual or incipient congestive heart failure. RBCs are
administered in the same fashion as whole blood
+ Packed red cells are prepared by centrifuging whole blood and is useful
in RBC exchange in chronic anemia's like thalassaemia
li) Leukocyte poor RBC:
+ Prepared during procuring blood or at the time of transfusion using
specially designed fiters.
+ Other methods include sedimentation, inverted centrifugation filtration
through nylon or cotton fibres, saline batch washing; frozen and thawed
red cells or blood through microaggregate filters. Major indications for
using leukocyte poor red cells are:
To prevent non-hemolytic febrile reactions.
To prevent alloimmunization by HLA antigen in case of perspective
organ transplant cases.
To minimize or avoid transmission of CMV. 18
To prevent transfusion associated graft vs host disease (TA-G VHD).
se Mo
+ Except for conditions which result in acute haemorrhage,
transfusion therapy is occasioned by the need to correct or
deficiency in a specific component of whole blood. The
rationale for component therapy stems from the recognition
that blood is a complex tissue with numerous constituents or
components, both cellular and noncellular, serving disease
functions. Component therapy permits the physician to
deliver an effective, therapeutic dose of the deficient
component with minimum risk of circulatory overload, or of
adverse reactions to the administration of unnecessary blood
components.
Blood components:
1. Erythrocyte preparations:
1. Packed red cells
2, Leucocyte poor red cell
3, Washed red cells
4, Frozen red cells
Il. Leukocytes:
1. Granulooytes
2, Mononuclear cells
Ill, Platelets
IV. Plasma fractions:
Fresh frozen plasma
2. Platelet rich plasma
3. Cryoprecipitate
4, Fractionated plasma
o Factor VIII concentrate
© Prothrombin complex concentration and factor IX
concentrate
o Albumin
© Immunoglobulin
© Antithrombin Ill concentrates
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Diagrammatic scheme of how whole blood is separated for component
therapy:
Whole |centituse [platelet Platelet | Freeze „[ Factor vit
blood rich plasma [ve "| poor plasma | 77e >| poor plasma
Free | row
200
y
Packed red Platelets Ciyoprecipitate
cell Fresh
free frozen La
bo plasma | thawing
| frozenred | [Leucocyte
cells poor red cells
|. Erythrocyte preparations:
1) Packed red blood cells:
+ The red cells from whole blood can be administered after removing
80% of the plasma, Packed red cells have a hematocrit of 60-90%.
+ RBCs, rather than whole blood, should be used for the treatment of all
patients who require a transfusion because of a red cell mass deficit
An absolute requirement for RBC exists, when transfusing anemic
patients with actual or incipient congestive heart failure. RBCs are
administered in the same fashion as whole blood
+ Packed red cells are prepared by centrifuging whole blood and is useful
in RBC exchange in chronic anemia's like thalassaemia
li) Leukocyte poor RBC:
+ Prepared during procuring blood or at the time of transfusion using
specially designed fiters.
+ Other methods include sedimentation, inverted centrifugation filtration
through nylon or cotton fibres, saline batch washing; frozen and thawed
red cells or blood through microaggregate filters. Major indications for
using leukocyte poor red cells are:
To prevent non-hemolytic febrile reactions.
To prevent alloimmunization by HLA antigen in case of perspective
organ transplant cases.
To minimize or avoid transmission of CMV. 18
To prevent transfusion associated graft vs host disease (TA-G VHD).
se Mo
[Blood Component therapy & Blood substitutes. Continuation:
Dr Azam's Notes in Anesthesiology 2013
iil) Washed red cells:
+ Usually obtained from whole blood. Packed red cells
obtained by centrifugation can be washed with saline using
either manual batch centrifugation or continuous flow
separator. Washed red cells should be used with in 24 hours
after processing because of the risk of bacterial
contamination (during processing). Washed red cells are
also prepared from blood salvaged during surgery.
Indications for washed red cells are
|. In patients who are hypersensitive to plasma.
IL Who develop allergic or febrile reactions following whole
blood transfusion.
Ill, Multiple transfusion patients
IV. Saline washed red cells are also indicated in case of
neonatal transfusions to reduce the quantity of metabolic
breakdown products, extra-cellular potassium and the risk
of CMV infusion.
V. To avoid TA-GVHD.
Frozen red cells:
+ After addition of a cryoprotective agent, RBC may be stored
continually below freezing temperatures. Freezing retards or
arrests the deleterious biochemical changes which occur
during liquid storage. Red blood cells can be frozen at -80°C
or below using 10% glycol as a preservative, and stored for
3-5 years or even more. They are leukocyte poor and
relatively plasma free.
+ Other advantages include availability of an inventory of rare
blood; promotion of component therapy; reduction in the
incidence of non hemolytic reactions; a ready supply of
metabolically superior red cells; reduction in sensitization to
histocompatibility antigens for potential transplant recipient
and a reduced incidence of transfusion hepatitis.
+ However the technology is complicated and the whole
process is expensive where one unit of frozen blood costs 3
times more than a unit of stored blood in liquid state.
Dr Azam's Notes in Anesthesiology 2013
Il. Leukocytes:
+ Less than 5% of the total body neutrophils pool is in the intravascular
space. These cells have a half life of only four to ten hours in the
intravascular compartment and are therefore rapidly replaced. The
collection of large number of granulocytes requires the processing of
between 5 to 10 liters of blood per donation.
1) Granulocytes:
The indications for granulocyte transfusion are not easy to define .In
general, the patient should have:
1. An absolute granulocyte count < 500/m!
2. Fever
3. Anunidentified microorganism
4, No decrease in fever after 48hrs of antibiotic treatment
ii) Mononuclear cells:
+ Collection of blood stem cells come under this category. Stem cells are
obtained for bone marrow transplant.
+ Blood stem cells make up a very small part of the circulating
mononuclear cell pool, cell separator techniques facilitate processing
large quantities of blood
+ Variety of substances like glucocorticoids, folinic acid, endotoxins help
release of stem cells into circulation, but the best currently used
substance is human growth factor.
+ Therapeutic use of peripheral stem cells is best cited in marrow
transplantation; in cases like AML; Hodgkin’s disease; multiple
myeloma; solid tumors like Carcinoma breast, ovarian Ca,
neuroblastoma etc.
Il, PLATELETS:
1) Random donor platelets (RDP):
+ ROP is collected from routine donations of whole blood. Each platelet
bag contains 7-10 x 10' platelets / unit. These platelets are suspended
in 40-50 ml of donor plasma to be stored at 20-22°C under constant
agitation for 5 days. Also has leukocyte contamination.
19
Dr Azam's Notes in Anesthesiology 2013
iil) Washed red cells:
+ Usually obtained from whole blood. Packed red cells
obtained by centrifugation can be washed with saline using
either manual batch centrifugation or continuous flow
separator. Washed red cells should be used with in 24 hours
after processing because of the risk of bacterial
contamination (during processing). Washed red cells are
also prepared from blood salvaged during surgery.
Indications for washed red cells are
|. In patients who are hypersensitive to plasma.
IL Who develop allergic or febrile reactions following whole
blood transfusion.
Ill, Multiple transfusion patients
IV. Saline washed red cells are also indicated in case of
neonatal transfusions to reduce the quantity of metabolic
breakdown products, extra-cellular potassium and the risk
of CMV infusion.
V. To avoid TA-GVHD.
Frozen red cells:
+ After addition of a cryoprotective agent, RBC may be stored
continually below freezing temperatures. Freezing retards or
arrests the deleterious biochemical changes which occur
during liquid storage. Red blood cells can be frozen at -80°C
or below using 10% glycol as a preservative, and stored for
3-5 years or even more. They are leukocyte poor and
relatively plasma free.
+ Other advantages include availability of an inventory of rare
blood; promotion of component therapy; reduction in the
incidence of non hemolytic reactions; a ready supply of
metabolically superior red cells; reduction in sensitization to
histocompatibility antigens for potential transplant recipient
and a reduced incidence of transfusion hepatitis.
+ However the technology is complicated and the whole
process is expensive where one unit of frozen blood costs 3
times more than a unit of stored blood in liquid state.
Dr Azam's Notes in Anesthesiology 2013
Il. Leukocytes:
+ Less than 5% of the total body neutrophils pool is in the intravascular
space. These cells have a half life of only four to ten hours in the
intravascular compartment and are therefore rapidly replaced. The
collection of large number of granulocytes requires the processing of
between 5 to 10 liters of blood per donation.
1) Granulocytes:
The indications for granulocyte transfusion are not easy to define .In
general, the patient should have:
1. An absolute granulocyte count < 500/m!
2. Fever
3. Anunidentified microorganism
4, No decrease in fever after 48hrs of antibiotic treatment
ii) Mononuclear cells:
+ Collection of blood stem cells come under this category. Stem cells are
obtained for bone marrow transplant.
+ Blood stem cells make up a very small part of the circulating
mononuclear cell pool, cell separator techniques facilitate processing
large quantities of blood
+ Variety of substances like glucocorticoids, folinic acid, endotoxins help
release of stem cells into circulation, but the best currently used
substance is human growth factor.
+ Therapeutic use of peripheral stem cells is best cited in marrow
transplantation; in cases like AML; Hodgkin’s disease; multiple
myeloma; solid tumors like Carcinoma breast, ovarian Ca,
neuroblastoma etc.
Il, PLATELETS:
1) Random donor platelets (RDP):
+ ROP is collected from routine donations of whole blood. Each platelet
bag contains 7-10 x 10' platelets / unit. These platelets are suspended
in 40-50 ml of donor plasma to be stored at 20-22°C under constant
agitation for 5 days. Also has leukocyte contamination.
19
[Blood Component therapy & Blood substitutes. Continuation:
ii) Single donor platelets:
» Prepared from single donor and each unit measures
250-300ml. No significant WBC contamination & can be
stored at 22°C under constant agitation for 5 days.
+ One unit platelet concentrate will increase platelet count by
5000/mm? to 10,000mm?.
INDICATIONS FOR PLATELET TRANSFUSION:
1) Thrombocytopenia with decreased platelet production
(Megakaryocyte thrombocytopenia)
Malignancy with cytoreductive therapy
Aplastic anemia
Myelodysplastic syndrome
2) Thrombocytopenia due to loss, destruction or sequestration
of platelets (megakaryocytic thrombocytopenia)
Platelet loss
Exsanguinations: replacement with stored blood
Cardiopulmonary bypass
a. Platelet sequestration
Splenomegaly
pic
b. Accelerated platelet destruction
Idiopathic thrombocytopenic purpura; ITP
Hereditary thrombocytopenia
- Neonatal isoimmune thrombocytopenia
3) Qualitative platelet disorders
Congenital
Acquired (myeloproliferative and myelodysplastic
syndrome)
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
IV. PLASMA FRACTIONS:
1) Fresh Frozen plasma (FFP):
FFP is the fluid portion of one unit of whole blood that is centrifuged,
separated & frozen solid at -18°C or lower, to be transfused within 6 hrs
of collection.
+ The initial volume of FFP transfused should be adequate to replace
deficient coagulation factors.
+ The average adult usually requires two to nine units of about 200m!
1
3.
each given over a period of a few hours. The Prothrombin time (PT)
and / or partial thromboplastin time (PTT) should be determined
immediately before and after transfusion
. Plasma not frozen within 8 hours or thawed after freezing and not
used within 24 hours has decreased levels of labile coagulation
factors V and factor Vill.
FFP contains factors IV, V, VII, VIII, IX along with naturally occurring
anticoagulants like protein C, protein S and also antithrombin Ill,
electrolytes, albumin, Immunoglobulins and complement proteins.
Each unit of FFP prepared from a single unit of blood will have a
volume of 200-250ml and by Plasmapharesis can be upto 1 lit-1.5iit
Indications of FFP:
Coagulation factor deficiency [2, 5, 7, 9, 10, 11, 13]
Reversal of warfarin effect
1
2.
3. Massive blood transfusion
4. Antithrombin III replacement
5.
6.
7,
8.
9.
‘Thrombotic thrombocytopenic purpura
. DIC
. Coagulopathy of liver disease
. Protein C or S deficiency
Hemolytic uremic syndrome
Dose of FFP: 1 unit for every 10 kg.
ii) Single donor platelets:
» Prepared from single donor and each unit measures
250-300ml. No significant WBC contamination & can be
stored at 22°C under constant agitation for 5 days.
+ One unit platelet concentrate will increase platelet count by
5000/mm? to 10,000mm?.
INDICATIONS FOR PLATELET TRANSFUSION:
1) Thrombocytopenia with decreased platelet production
(Megakaryocyte thrombocytopenia)
Malignancy with cytoreductive therapy
Aplastic anemia
Myelodysplastic syndrome
2) Thrombocytopenia due to loss, destruction or sequestration
of platelets (megakaryocytic thrombocytopenia)
Platelet loss
Exsanguinations: replacement with stored blood
Cardiopulmonary bypass
a. Platelet sequestration
Splenomegaly
pic
b. Accelerated platelet destruction
Idiopathic thrombocytopenic purpura; ITP
Hereditary thrombocytopenia
- Neonatal isoimmune thrombocytopenia
3) Qualitative platelet disorders
Congenital
Acquired (myeloproliferative and myelodysplastic
syndrome)
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
IV. PLASMA FRACTIONS:
1) Fresh Frozen plasma (FFP):
FFP is the fluid portion of one unit of whole blood that is centrifuged,
separated & frozen solid at -18°C or lower, to be transfused within 6 hrs
of collection.
+ The initial volume of FFP transfused should be adequate to replace
deficient coagulation factors.
+ The average adult usually requires two to nine units of about 200m!
1
3.
each given over a period of a few hours. The Prothrombin time (PT)
and / or partial thromboplastin time (PTT) should be determined
immediately before and after transfusion
. Plasma not frozen within 8 hours or thawed after freezing and not
used within 24 hours has decreased levels of labile coagulation
factors V and factor Vill.
FFP contains factors IV, V, VII, VIII, IX along with naturally occurring
anticoagulants like protein C, protein S and also antithrombin Ill,
electrolytes, albumin, Immunoglobulins and complement proteins.
Each unit of FFP prepared from a single unit of blood will have a
volume of 200-250ml and by Plasmapharesis can be upto 1 lit-1.5iit
Indications of FFP:
Coagulation factor deficiency [2, 5, 7, 9, 10, 11, 13]
Reversal of warfarin effect
1
2.
3. Massive blood transfusion
4. Antithrombin III replacement
5.
6.
7,
8.
9.
‘Thrombotic thrombocytopenic purpura
. DIC
. Coagulopathy of liver disease
. Protein C or S deficiency
Hemolytic uremic syndrome
Dose of FFP: 1 unit for every 10 kg.
[Blood Component therapy & Blood substitutes. Continuation:
2) Cryoprecipitate:
+ Cryoprecipitate is prepared by thawing FFP at 4% and
removing the supernatant. Three major classes of plasma
derivatives are obtained from the cryoprecipitate ie ;
coagulation factors VIII and IX; immunoglobulin and albumin
preparations.
+ One unit of cryoprecipitate will have a volume of approx
10-20ml and should contain 80-120 units of factor Vill and
100-250m of fibrinogen.
Indications:
Factors VIII and von Willebrand factor replacement.
Fibrinogen replacement (a/dys/hypo-fibrinogenemia)
Factor XIII replacement (| in trauma, bums and sepsis)
Fibrin sealant — a combination of thrombin and
eryoprecipitate.
sn on
Dr Azam's Notes in Anesthesiology 2013
Coagulum pyelotomy - a coagulum formed by the addition
of thrombin and calcium to cryoprecipitate is used to entrap
calculi in the renal pelvis to facilitate pyelotomy removal.
Dr Azam's Notes in Anesthesiology 2013
Replacement therapy for coagulation factor deficiency:
Factor [Terapeutc dose [Component /derivatives
Fibrinogen | unite /Bkg body Eryoprecipilate(100-250gme
wt fibrinogen bag)
fi) Prothrombin [10-20m! plasma /k¢ ma or prothrombin complex
Factor V [20ml fresh frozen
iasmaikg
fi) Factor VII [10-20m plasma/kg Plasma or prothrombin complex
centrate
Factor vil” [(S-S0unitskg Cryoprecipitate (100 untsbag) factor
ill concentrate
i) Factors IX [20-80 unitskg ’rothrombin complex concentrate
jlasma (1 unit of factor IX/ml)
il) Factor X [10-20ml plasma/kg Plasma or prothrombin complex
Factor XI_|10-20mi plasmalkg Plasma
9 Factor Xi }-6 bags Plasma or Cryopreciptate
ryopreciptate or
0m! plasma
V. Albumin:
+ The source material is whole blood plasma, serum or placenta. At least
96% of the total protein in the final product is albumin. The derivative is
available in 5% and 25% solutions. Plasma protein fractions containing
albumin and globulins are available for use as volume expanders. They
can be given without regard to ABO blood type. They are expensive
and are in short supply. They should be administered within 4 hours of
starting the infusion.
Indications:
1. Hypoproteinemia
2. Bums
3. Peritonitis
Vi. Intravenous immunoglobulins:
Indications:
1. Viral infections: CMV
2. ITP
3. Posttransfusion purpura
4. Thrombotic thrombocytopenic purpura
2
2) Cryoprecipitate:
+ Cryoprecipitate is prepared by thawing FFP at 4% and
removing the supernatant. Three major classes of plasma
derivatives are obtained from the cryoprecipitate ie ;
coagulation factors VIII and IX; immunoglobulin and albumin
preparations.
+ One unit of cryoprecipitate will have a volume of approx
10-20ml and should contain 80-120 units of factor Vill and
100-250m of fibrinogen.
Indications:
Factors VIII and von Willebrand factor replacement.
Fibrinogen replacement (a/dys/hypo-fibrinogenemia)
Factor XIII replacement (| in trauma, bums and sepsis)
Fibrin sealant — a combination of thrombin and
eryoprecipitate.
sn on
Dr Azam's Notes in Anesthesiology 2013
Coagulum pyelotomy - a coagulum formed by the addition
of thrombin and calcium to cryoprecipitate is used to entrap
calculi in the renal pelvis to facilitate pyelotomy removal.
Dr Azam's Notes in Anesthesiology 2013
Replacement therapy for coagulation factor deficiency:
Factor [Terapeutc dose [Component /derivatives
Fibrinogen | unite /Bkg body Eryoprecipilate(100-250gme
wt fibrinogen bag)
fi) Prothrombin [10-20m! plasma /k¢ ma or prothrombin complex
Factor V [20ml fresh frozen
iasmaikg
fi) Factor VII [10-20m plasma/kg Plasma or prothrombin complex
centrate
Factor vil” [(S-S0unitskg Cryoprecipitate (100 untsbag) factor
ill concentrate
i) Factors IX [20-80 unitskg ’rothrombin complex concentrate
jlasma (1 unit of factor IX/ml)
il) Factor X [10-20ml plasma/kg Plasma or prothrombin complex
Factor XI_|10-20mi plasmalkg Plasma
9 Factor Xi }-6 bags Plasma or Cryopreciptate
ryopreciptate or
0m! plasma
V. Albumin:
+ The source material is whole blood plasma, serum or placenta. At least
96% of the total protein in the final product is albumin. The derivative is
available in 5% and 25% solutions. Plasma protein fractions containing
albumin and globulins are available for use as volume expanders. They
can be given without regard to ABO blood type. They are expensive
and are in short supply. They should be administered within 4 hours of
starting the infusion.
Indications:
1. Hypoproteinemia
2. Bums
3. Peritonitis
Vi. Intravenous immunoglobulins:
Indications:
1. Viral infections: CMV
2. ITP
3. Posttransfusion purpura
4. Thrombotic thrombocytopenic purpura
2
[Blood Component therapy & Blood substitutes. Continuation:
Dr Azam's Notes in Anesthesiology 2013
Vil. Antithrombin Il concentrates:
+ Antithrombin III deficiency:
+ Shock and DIC
Vill, Factors Vill concentrates:
+ Used in treatment of hemophilia A
1X Factor IX concentrates:
- Used in treatment of hemophilia B
Hazards of component therapy:
+ All hazards of blood transfusion are applicable to transfusion
of components also:
Immediate reactions:
Febrile reactions
Allergic reactions
Transfusion Related Acute Lung Injury - TRALI
Acute hemolytic transfusion reactions
Sensitivity to leukocytes and platelets
Non cardiogenic pulmonary oedema
Bacterial contamination
Bleeding syndrome
Circulatory overload
10. Air embolism
Delayed reactions:
Delayed hemolytic reactions
Post transfusion purpura
TA-GVHD
Transmission of diseases like hepatitis B, hepatitis C,
HIV, CMV, HTLV3 ete.
veenounsun-
Aone
Dr Azam's Notes in Anesthesiology 2013
Blood substitutes:
+ Some functions such as maintaining circulatory volume and oncotic
pressure can be replaced with various crystalloids and colloid
macromolecules such as Dextrans and Hydroxyethyl starch.
[Substitute Half lite Reaction [Mechanism
Dextran mol m 75,000 hrs Mid Allergie.
Mol. wt 40,000 E hrs Severe JAnti-dextran antibodies
Gelatin 35,000 B-hrs — [mmediate [Histamine release
{Starch 4,50,000 [hrs Immediate [Complement activation
These, however do not provide for oxygen transport.
Red cell substitutes:
2 main indications:
+ Severe haemorrhage
+ Chronic symptomatic anemia for which no specific therapy exists.
+ In both circumstances, the aim of red cell transfusion is to improve the
O2 supply to the tissues by raising the O2 content of blood according to
the equation.
O2 delivery = cardiac output x arterial O2 content
Arterial O2 content = Hb cone. x % saturation x 1.34
‘Oxygen Flux = Cardiac output x Hb x % saturation x 1.34
(Variables are CO, Hb, saturation)
Perfluorocompounds:
+ Perfluorochemical are large organic compounds in which all the
hydrogen atoms are replaced by fluorine. A unit volume of
perfluorochemical carries almost three times the oxygen carried by a
similar volume of blood. They are chemically inert and not metabolized,
but require emulsification with surfactants to be miscible with blood.
) Fluosol-DA:
+ A 20% emulsion of 2 different Perfluorocompounds described as
FLUOSOL-DA which has O2 carrying capacity at 37°C of about 40% of
that of red cells
Dose: 20mi/kg
Side effects:
+ Pulmonary reactions; cytotoxicity; complement activation; retention of
the product in the liver and spleen and vulnerability to oxygen #6xicity.
Dr Azam's Notes in Anesthesiology 2013
Vil. Antithrombin Il concentrates:
+ Antithrombin III deficiency:
+ Shock and DIC
Vill, Factors Vill concentrates:
+ Used in treatment of hemophilia A
1X Factor IX concentrates:
- Used in treatment of hemophilia B
Hazards of component therapy:
+ All hazards of blood transfusion are applicable to transfusion
of components also:
Immediate reactions:
Febrile reactions
Allergic reactions
Transfusion Related Acute Lung Injury - TRALI
Acute hemolytic transfusion reactions
Sensitivity to leukocytes and platelets
Non cardiogenic pulmonary oedema
Bacterial contamination
Bleeding syndrome
Circulatory overload
10. Air embolism
Delayed reactions:
Delayed hemolytic reactions
Post transfusion purpura
TA-GVHD
Transmission of diseases like hepatitis B, hepatitis C,
HIV, CMV, HTLV3 ete.
veenounsun-
Aone
Dr Azam's Notes in Anesthesiology 2013
Blood substitutes:
+ Some functions such as maintaining circulatory volume and oncotic
pressure can be replaced with various crystalloids and colloid
macromolecules such as Dextrans and Hydroxyethyl starch.
[Substitute Half lite Reaction [Mechanism
Dextran mol m 75,000 hrs Mid Allergie.
Mol. wt 40,000 E hrs Severe JAnti-dextran antibodies
Gelatin 35,000 B-hrs — [mmediate [Histamine release
{Starch 4,50,000 [hrs Immediate [Complement activation
These, however do not provide for oxygen transport.
Red cell substitutes:
2 main indications:
+ Severe haemorrhage
+ Chronic symptomatic anemia for which no specific therapy exists.
+ In both circumstances, the aim of red cell transfusion is to improve the
O2 supply to the tissues by raising the O2 content of blood according to
the equation.
O2 delivery = cardiac output x arterial O2 content
Arterial O2 content = Hb cone. x % saturation x 1.34
‘Oxygen Flux = Cardiac output x Hb x % saturation x 1.34
(Variables are CO, Hb, saturation)
Perfluorocompounds:
+ Perfluorochemical are large organic compounds in which all the
hydrogen atoms are replaced by fluorine. A unit volume of
perfluorochemical carries almost three times the oxygen carried by a
similar volume of blood. They are chemically inert and not metabolized,
but require emulsification with surfactants to be miscible with blood.
) Fluosol-DA:
+ A 20% emulsion of 2 different Perfluorocompounds described as
FLUOSOL-DA which has O2 carrying capacity at 37°C of about 40% of
that of red cells
Dose: 20mi/kg
Side effects:
+ Pulmonary reactions; cytotoxicity; complement activation; retention of
the product in the liver and spleen and vulnerability to oxygen #6xicity.
[Blood Component therapy & Blood substitutes.Continuation: Dr Azam's Notes in Anesthesiology 2013
li) Polyfluoro-octobromide (Perflubron):
+ Itis a newer Perfluorocompounds (radiopaque)
+ Has 2 advantages
+ Higher concentration of the compound can be administered
because 100% emulsion with a phospholipids has a sufficiently
low viscosity to be infused without dilution,
+ Ozis more soluble in perflubron
+ Itcan carry as much Oz as a Hb solution at a cone. of 7gm/dl.
Conclusion:
+ Red cell substitutes under trial have too short a survival time in
Circulation to be substitutes for red cell in treatment of chronic
anemia.
+ They can be used in short term procedures, such as immediate
resuscitation and in intra operative haemodilution, red cell has
to be transfused within next 24 hrs.
Dr Azam's Notes in Anesthesiology 2013
li) Polyfluoro-octobromide (Perflubron):
+ Itis a newer Perfluorocompounds (radiopaque)
+ Has 2 advantages
+ Higher concentration of the compound can be administered
because 100% emulsion with a phospholipids has a sufficiently
low viscosity to be infused without dilution,
+ Ozis more soluble in perflubron
+ Itcan carry as much Oz as a Hb solution at a cone. of 7gm/dl.
Conclusion:
+ Red cell substitutes under trial have too short a survival time in
Circulation to be substitutes for red cell in treatment of chronic
anemia.
+ They can be used in short term procedures, such as immediate
resuscitation and in intra operative haemodilution, red cell has
to be transfused within next 24 hrs.
Dr Azam's Notes in Anesthesiology 2013
[B. Define Massive blood transfusion. Discuss the complications associated with massive blood Dr Azam's Notes in Anesthesiology 2013
transfusion.
Definition:
+ Massive blood transfusion may be defined either as the acute administration of more than 1.5
times the patients total blood volume by homologous blood in less than 24 hours.
Also defined as:
+ Transfusion of one pint of blood with in 5 minutes;
+ Transfusion of 5 units within 1 hr
+ Transfusion of 10 units within Ghrs,
+ Transfusion of >10% of blood volume within 10 minutes.
(Complications of Massive Blood transfusion:
\
Earl
5 Late
+ Hemolytic reacti
immédiats - Transmission of infection
Delayed Viral (hepatitis A, B, C, HIV, CMV)
+ Non-hemolytic febrile reactions Bacterial (Salmonella), Parasites (Malaria,
+ Allergic reactions to proteins, IgA Toxoplasma)
+ Transfusion-related acute lung injury + Graft-vs-host disease
+ Reactions secondary to bacterial contamination Circulatory + TRIM - Transfusion related immunomodulation
overload + Iron overload (after chronic transfusions)
+ Air embolism + Immune sensitization (Rhesus D antigen)
+ Thrombophlebitis
+ Hyperkalaemia
+ Citrate toxicity
+ Hypothermia
+ Clotting abnormalities (after massive transfusion)
2
Dr Azants Notes in Anesthesiology 2013
transfusion.
Definition:
+ Massive blood transfusion may be defined either as the acute administration of more than 1.5
times the patients total blood volume by homologous blood in less than 24 hours.
Also defined as:
+ Transfusion of one pint of blood with in 5 minutes;
+ Transfusion of 5 units within 1 hr
+ Transfusion of 10 units within Ghrs,
+ Transfusion of >10% of blood volume within 10 minutes.
(Complications of Massive Blood transfusion:
\
Earl
5 Late
+ Hemolytic reacti
immédiats - Transmission of infection
Delayed Viral (hepatitis A, B, C, HIV, CMV)
+ Non-hemolytic febrile reactions Bacterial (Salmonella), Parasites (Malaria,
+ Allergic reactions to proteins, IgA Toxoplasma)
+ Transfusion-related acute lung injury + Graft-vs-host disease
+ Reactions secondary to bacterial contamination Circulatory + TRIM - Transfusion related immunomodulation
overload + Iron overload (after chronic transfusions)
+ Air embolism + Immune sensitization (Rhesus D antigen)
+ Thrombophlebitis
+ Hyperkalaemia
+ Citrate toxicity
+ Hypothermia
+ Clotting abnormalities (after massive transfusion)
2
Dr Azants Notes in Anesthesiology 2013
[Complications of Massive Blood transfusion:
i eee
Dr Azam’s Notes in Anesthesiology 2013
Early
y
[Citrate toxicity: in
[Clotting abnormalities (after
[ Hemolytic reactions Toriizad calalum
= Inmedials massive transfusion)
- Delayed
y y
y
A massive transfusion of red blood
cells (RBCs) may lead to a
+ Dilutional Coagulopathy,
Citrate binds calcium, thus lowering the
ionized plasma calcium concentration.
This is usually prevented by rapid hepatic
The most serious complications of blood
transfusion result from interactions
+ Consumptive coagulopathy,
between antibodies in the recipient's. Thrombeeytepania,
plasma and surface antigens on donor
RBOS. — - Incompatible blood
M
Signs and symptoms of
hemolytic transfusion reaction:
+ Fever and chills
y
Treatment
+ Administration of platelets and FFP
+ Dose: 1 Unit of FFP for every 10 kg
- Chest pain + 2 unit FFP for each 10unit of blood transfused
+ Hypotension + 6 unit Platelet concentration for every 20u of
+ Nausea blood transfused
+ Flushing + Basic screening tests for bleeding after surgery--
+ Dyspnoea Platelet count; prothrombin time; APTT, plasma
+ Hemoglobinuria fibrinogen concentration and fibrinogen
degradation products when indicated.
NX Treatment of Hemolytic reaction:
1. Stop the transfusion
IL. Maintain the urine output at a minimum of 75-100mi/hr
Il. Alkalinize the urine
Send patient blood and urine sample to blood bank for examination.
Prevent hypotension to ensure adequate renal blood flow.
Maintain IV line, O2 therapy; resuscitative measures.
Antihistamine — diphenhydramine 0.5-1mg/Kg IV.
Steroid - hydrocortisone — 2-4mg/kg IV.
Antibiotics
orapp=
metabolism unless the patient is
hypothermic
Treatment
+ Calcium gluconate 10ml 10% over 10 min
+ is less effective than calcium chloride
because it must be metabolized to be
effective,
+ 13.4% calcium chloride containing calcium
0.192 mmol/m is more effective than the
weaker 10% calcium gluconate solution which
contains only 0.22mmol/m of calcium,
+ Massive transfusion with PRBC alone causes
a dilutional coagulopathy.
+ Massive hemorthage causes consumptive
coagulopathy.
25
Dr Azam's Notes in Anesthesiology 2013
i eee
Dr Azam’s Notes in Anesthesiology 2013
Early
y
[Citrate toxicity: in
[Clotting abnormalities (after
[ Hemolytic reactions Toriizad calalum
= Inmedials massive transfusion)
- Delayed
y y
y
A massive transfusion of red blood
cells (RBCs) may lead to a
+ Dilutional Coagulopathy,
Citrate binds calcium, thus lowering the
ionized plasma calcium concentration.
This is usually prevented by rapid hepatic
The most serious complications of blood
transfusion result from interactions
+ Consumptive coagulopathy,
between antibodies in the recipient's. Thrombeeytepania,
plasma and surface antigens on donor
RBOS. — - Incompatible blood
M
Signs and symptoms of
hemolytic transfusion reaction:
+ Fever and chills
y
Treatment
+ Administration of platelets and FFP
+ Dose: 1 Unit of FFP for every 10 kg
- Chest pain + 2 unit FFP for each 10unit of blood transfused
+ Hypotension + 6 unit Platelet concentration for every 20u of
+ Nausea blood transfused
+ Flushing + Basic screening tests for bleeding after surgery--
+ Dyspnoea Platelet count; prothrombin time; APTT, plasma
+ Hemoglobinuria fibrinogen concentration and fibrinogen
degradation products when indicated.
NX Treatment of Hemolytic reaction:
1. Stop the transfusion
IL. Maintain the urine output at a minimum of 75-100mi/hr
Il. Alkalinize the urine
Send patient blood and urine sample to blood bank for examination.
Prevent hypotension to ensure adequate renal blood flow.
Maintain IV line, O2 therapy; resuscitative measures.
Antihistamine — diphenhydramine 0.5-1mg/Kg IV.
Steroid - hydrocortisone — 2-4mg/kg IV.
Antibiotics
orapp=
metabolism unless the patient is
hypothermic
Treatment
+ Calcium gluconate 10ml 10% over 10 min
+ is less effective than calcium chloride
because it must be metabolized to be
effective,
+ 13.4% calcium chloride containing calcium
0.192 mmol/m is more effective than the
weaker 10% calcium gluconate solution which
contains only 0.22mmol/m of calcium,
+ Massive transfusion with PRBC alone causes
a dilutional coagulopathy.
+ Massive hemorthage causes consumptive
coagulopathy.
25
Dr Azam's Notes in Anesthesiology 2013
[Complications of Massive Blood transfusion: Continuation
y
FHyperkalemia:
F Acid-base disturbances:
y
The potassium
concentration of blood
increases during storage,
by as much as 5-
10mmol. After
transfusion, the RBC
membrane Na+-K+
ATPase pumping
mechanism is re-
established and cellular
potassium re-uptake
occurs rapidly.
+ Transfusion of
>7 units of
PRECs,
associated with
independently
increases
Potassium.
Each unit of RBCs
contains 1-2mmol of
acid. This is generated
from the citric acid of the
anticoagulant and from
the lactic acid produced
during storage;
metabolism of this acid is
usually very rapid.
Treatment:
+ Adequate fluid
resuscitation
+ At times may
require
Bicarbonate
therapy
Note:
+ 10% reduction in
coagulation for 1 °C
drop in
temperature.
- Hypothermia:
RBCs are stored at 4 °C. Rapid
transfusion at this temperature will
quickly lower the recipient's core
temperature and further impair
haemostasis. Hypothermia reduces
the metabolism of citrate and lactate
and increases the likelihood of
hypocalcaemia, metabolic acidosis
and cardiac arrhythmias, Peripheral
coagulopathy, vasoconstriction,
Infection.
Treatment:
+ This reduction in temperature can
be minimized by warming all IV
+ Fluids and by the use of forced air
convection warming blankets to
reduce radiant heat loss.
+ Reduction in coagulation factors for
each 1 °C, drop in temperature,
+ CT is prolonged below 33 °C.
+ Increase room temperature.
+ Surface wating the patient with
heating blanket, heating lamps.
+ Heated & humidified inspiration
gases.
+ Using blood and fluid warmer.
Dr Azam’s Notes in Anesthesiology 2013
Early — NIIT
—_ 7, >
[- Transfusion-related acute lung Injury
+ Ocours during or within 6 hours of
transfusion.
+ Two different mechanisms for the
pathogenesis of TRALI :
+ Immune (Antibody mediated)
+ Non-immune.
+ Immune TRALI results from
the presence of leucocyte
antibodies in the plasma of
donor blood, directed
against human leucocyte
antigens (HLA) and human
neutrophil alloantigens
(HNA) in the recipient.
26
Dr Azam's Notes in Anesthesiology 2013
y
FHyperkalemia:
F Acid-base disturbances:
y
The potassium
concentration of blood
increases during storage,
by as much as 5-
10mmol. After
transfusion, the RBC
membrane Na+-K+
ATPase pumping
mechanism is re-
established and cellular
potassium re-uptake
occurs rapidly.
+ Transfusion of
>7 units of
PRECs,
associated with
independently
increases
Potassium.
Each unit of RBCs
contains 1-2mmol of
acid. This is generated
from the citric acid of the
anticoagulant and from
the lactic acid produced
during storage;
metabolism of this acid is
usually very rapid.
Treatment:
+ Adequate fluid
resuscitation
+ At times may
require
Bicarbonate
therapy
Note:
+ 10% reduction in
coagulation for 1 °C
drop in
temperature.
- Hypothermia:
RBCs are stored at 4 °C. Rapid
transfusion at this temperature will
quickly lower the recipient's core
temperature and further impair
haemostasis. Hypothermia reduces
the metabolism of citrate and lactate
and increases the likelihood of
hypocalcaemia, metabolic acidosis
and cardiac arrhythmias, Peripheral
coagulopathy, vasoconstriction,
Infection.
Treatment:
+ This reduction in temperature can
be minimized by warming all IV
+ Fluids and by the use of forced air
convection warming blankets to
reduce radiant heat loss.
+ Reduction in coagulation factors for
each 1 °C, drop in temperature,
+ CT is prolonged below 33 °C.
+ Increase room temperature.
+ Surface wating the patient with
heating blanket, heating lamps.
+ Heated & humidified inspiration
gases.
+ Using blood and fluid warmer.
Dr Azam’s Notes in Anesthesiology 2013
Early — NIIT
—_ 7, >
[- Transfusion-related acute lung Injury
+ Ocours during or within 6 hours of
transfusion.
+ Two different mechanisms for the
pathogenesis of TRALI :
+ Immune (Antibody mediated)
+ Non-immune.
+ Immune TRALI results from
the presence of leucocyte
antibodies in the plasma of
donor blood, directed
against human leucocyte
antigens (HLA) and human
neutrophil alloantigens
(HNA) in the recipient.
26
Dr Azam's Notes in Anesthesiology 2013
[Complications of Massive Blood transfusion: Continuation
|
Dr Azanrs Notes in Anesthesiology 2013
« Transfusion-related infections]
Bacterial
Bacterial contamination of blood components
is an infrequent complication of transfusion.
+ Brucella
+ Pseudomonas
+ Salmonella
+ Shigella
Viral
The incidence of transfusion-related viral
infection has greatly reduced
+ Cytomegalovirus (Incidence 1:10 to 1:30)
+ Hepatitis
+ HIV (Incidence 1:50000)
+ Epstein barr virus
+ Herpes simplex
+ Measles
Parasites:
+ Malaria
+ Toxoplasmosis
Incidence:
+ HCV
+ EBV
Dr Azanr's Notes in Anesthesiology 2013
[+ Transfusion-associated
as [+ Immunomodulation
The potential to modulate the
s immune system of transfusion
Transfusion-associated graft-vs- recipients remains an exciting
host disease (GVHD) is a very rare but controversial erea of
complication of blood transfusion transfusion medicine.
+ Non-haemolytic febrile reactions
These reactions are very common and are usually not life-threatening. Reacti
result from donor leucocyte antigens reacting to antibodies present in the recipient's
plasma,
+ Allergic reactions
Allergic reactions are common and usually mild. The majority are due to the
presence of foreign proteins in donor plasma and are IgE-mediated. Pruritus and
urticaria, with or without fever, are the most common features. The transfusion
should be stopped and anti- histamines administered.
‘Treatment is he same as for anaphylaxis from other causes, with IV fluid
resuscitation, epinephrine administration (to reestablish vasomotor tone and reverse
bronchospasm), antihistamines, corticosteroids and respiratory support. If
subsequent transfusions are required in such patients, washed RBCs should be
used (residual plasma and therefore IgA is removed).
27
|
Dr Azanrs Notes in Anesthesiology 2013
« Transfusion-related infections]
Bacterial
Bacterial contamination of blood components
is an infrequent complication of transfusion.
+ Brucella
+ Pseudomonas
+ Salmonella
+ Shigella
Viral
The incidence of transfusion-related viral
infection has greatly reduced
+ Cytomegalovirus (Incidence 1:10 to 1:30)
+ Hepatitis
+ HIV (Incidence 1:50000)
+ Epstein barr virus
+ Herpes simplex
+ Measles
Parasites:
+ Malaria
+ Toxoplasmosis
Incidence:
+ HCV
+ EBV
Dr Azanr's Notes in Anesthesiology 2013
[+ Transfusion-associated
as [+ Immunomodulation
The potential to modulate the
s immune system of transfusion
Transfusion-associated graft-vs- recipients remains an exciting
host disease (GVHD) is a very rare but controversial erea of
complication of blood transfusion transfusion medicine.
+ Non-haemolytic febrile reactions
These reactions are very common and are usually not life-threatening. Reacti
result from donor leucocyte antigens reacting to antibodies present in the recipient's
plasma,
+ Allergic reactions
Allergic reactions are common and usually mild. The majority are due to the
presence of foreign proteins in donor plasma and are IgE-mediated. Pruritus and
urticaria, with or without fever, are the most common features. The transfusion
should be stopped and anti- histamines administered.
‘Treatment is he same as for anaphylaxis from other causes, with IV fluid
resuscitation, epinephrine administration (to reestablish vasomotor tone and reverse
bronchospasm), antihistamines, corticosteroids and respiratory support. If
subsequent transfusions are required in such patients, washed RBCs should be
used (residual plasma and therefore IgA is removed).
27
9. Describe Anesthetics concerns for regional anesthesia in a patient on anticoagulants.
+ Guidelines based on literature, case studies, and consensus statements
+ The morbidity of spinal hematomas can be greatly reduced with early diagnosis and intervention.
+ Neurological monitoring at least every 2hrs should be considered in high-risk situations.
+ Consider using neuraxial infusions with low doses of local anesthetic in higher risk situations.
+ This will enhance early detection of spinal hematoma
+ Combined therapies, which attack unique components of the coagulation cascade, may increase the risk of bleeding complications. (e.g. Heparin AND coumadin)
+ Approach new agents affecting coagulation with caution.(e.g Fondaparinux)
_
F Thrombolytics
+ Consider avoiding neuraxial
blocks, except in extreme
circumstances, Time block at
least 10 days after, and 10 days
before thrombolytics given.
+ If thrombolytics are given
around the time of neuraxial
puncture, monitor patients at
least Q2hrs, and use solutions
with weak local anesthetic.
+ No recommendation for timing
of catheter removal after
unexpected thrombolytics use.
+ Use caution and consider
checking fibrinogen levels.
Eg:
+ Alteplase
+ Reteplase
+ Streptokinase
+ Urokinase
Dr Azam's Notes in Anesthesiology 2013
[Regional anesthesia In a patient on anticoagulants - ASRA
y
[- Heparin- Unfractionated
Subeutaneous Heparin
+ No contraindication for neuraxial techniques
with mini-dose SQ heparin
+ Time insertion of needle or removal of
catheters 4 hours after last dose, and 2-4
hours before subsequent dose.
+ Consider checking a platelet count in patients
receiving SQ heparin for greater than 4 days,
to rule out heparin-induced thrombocytopenia
IT)
Low dose intra-operative heparin
+ Delay heparin dose for 1 hr after needle
placement. Remove catheter 1 hr before any
subsequent dose, or 2-4 hrs after last dose,
+ Consider postoperative monitoring (q2hr
neuro checks) and using weak local
anesthetic concentrations.
Prolonged therapeutic heparinization
+ Neuraxial blocks should be avoided in this
situation
y
| Low Molecular
Weight Heparin
(LMWR)
High Dose-BID LMWH
(eg. enoxaprin Img/kg ql2hr, or 1.5mg/
kgQD)
« First dose should be given >24hrs after
the block, and 2 hrs after catheter
removal
+ Indwelling catheters should be removed
prior to initiating therapy
LowDose-QDLMWH
(EuropeanRegimen)
+ Indwelling neuraxial catheters can be
safely maintained.
+ First dose of LMWH should be given 6-8
hrs after block
+ Catheter should be removed >10-12 hrs
after the last dose. o Subsequent dose of
LMWH given>2 hrs after removal of
catheter.
28
Dr Azam’s Notes in Anesthesiology 2013
+ Guidelines based on literature, case studies, and consensus statements
+ The morbidity of spinal hematomas can be greatly reduced with early diagnosis and intervention.
+ Neurological monitoring at least every 2hrs should be considered in high-risk situations.
+ Consider using neuraxial infusions with low doses of local anesthetic in higher risk situations.
+ This will enhance early detection of spinal hematoma
+ Combined therapies, which attack unique components of the coagulation cascade, may increase the risk of bleeding complications. (e.g. Heparin AND coumadin)
+ Approach new agents affecting coagulation with caution.(e.g Fondaparinux)
_
F Thrombolytics
+ Consider avoiding neuraxial
blocks, except in extreme
circumstances, Time block at
least 10 days after, and 10 days
before thrombolytics given.
+ If thrombolytics are given
around the time of neuraxial
puncture, monitor patients at
least Q2hrs, and use solutions
with weak local anesthetic.
+ No recommendation for timing
of catheter removal after
unexpected thrombolytics use.
+ Use caution and consider
checking fibrinogen levels.
Eg:
+ Alteplase
+ Reteplase
+ Streptokinase
+ Urokinase
Dr Azam's Notes in Anesthesiology 2013
[Regional anesthesia In a patient on anticoagulants - ASRA
y
[- Heparin- Unfractionated
Subeutaneous Heparin
+ No contraindication for neuraxial techniques
with mini-dose SQ heparin
+ Time insertion of needle or removal of
catheters 4 hours after last dose, and 2-4
hours before subsequent dose.
+ Consider checking a platelet count in patients
receiving SQ heparin for greater than 4 days,
to rule out heparin-induced thrombocytopenia
IT)
Low dose intra-operative heparin
+ Delay heparin dose for 1 hr after needle
placement. Remove catheter 1 hr before any
subsequent dose, or 2-4 hrs after last dose,
+ Consider postoperative monitoring (q2hr
neuro checks) and using weak local
anesthetic concentrations.
Prolonged therapeutic heparinization
+ Neuraxial blocks should be avoided in this
situation
y
| Low Molecular
Weight Heparin
(LMWR)
High Dose-BID LMWH
(eg. enoxaprin Img/kg ql2hr, or 1.5mg/
kgQD)
« First dose should be given >24hrs after
the block, and 2 hrs after catheter
removal
+ Indwelling catheters should be removed
prior to initiating therapy
LowDose-QDLMWH
(EuropeanRegimen)
+ Indwelling neuraxial catheters can be
safely maintained.
+ First dose of LMWH should be given 6-8
hrs after block
+ Catheter should be removed >10-12 hrs
after the last dose. o Subsequent dose of
LMWH given>2 hrs after removal of
catheter.
28
Dr Azam’s Notes in Anesthesiology 2013
[Regional anesthesia in a patient on anticoagulants
y
F Coumadin/Warfarin:
+ Chronic oral anticoagulation should be
stopped 4-5 days prior to block, and PT/
INR checked before procedure
performed.
+ If initial dose given >24 hrs prior to
procedure or if 2 or more doses given,
check PT/INR before block.
+ Catheters can be safely maintained on
low dose (5mg) warfarin therapy
CheckPT/INR QD for indwelling catheter
in pts on warfarin
+ If INF > 3, with hold or reduce coumadin
dose,
+ Catheters can be removed when INR <
15.
+ Minimize local anesthetic concentration;
monitor neuro status during therapy and
for 24hrs after catheter removal
Dr Azam's Notes in Anesthesiology 2013
[CAnti-platelet Medications
+ Includes NSAIDS
(motrin naproxen) thienopyridines(ticlopidine
and clopidogrel), glycoprotein Ilb/lla
antagonists (abciximab, tirofiban)
+ Bleeding time not a reliable test. Risk for
bleeding increased in females, elderly, and
those with a history of easy bruising/
excessive bleeding.
+ NSAIDS-no added risk or timing concems
for neuraxial techniques when used alone.
Ticlopidine,clopidogrel, and platelet GP
antagonist may represent significant risk:
+ Tielopidine- discontinue 14 days prior to
block Clopidogrel- discontinue 7 days prior
to block
+ Abciximab- discontinue 2 days prior
+ Eptifibatide and tirofiban- discontinue Bhrs
prior to block (GPlIbAlla)
Cox-2selective inhibitors(rofecoxib, celecoxib,
valdecoxib)
+ Minimal effect of platelet function.
+ Consider in patients requiring anti-
inflammatory peri-operatively.
A Dr Azam’s Notes in Anesthesiology 2013
F Fondaparinux
+ Anti-thrombotic effect through factor Xa
inhibition, actual risk unknown.
+ Consensus recommendations based on the
sustained and irreversible anti thrombotic effect,
early postoperative dosing, and report of spinal
hematoma reported during initial clinical trials,
+ Recommend single needle pass, atraumatic
needle placement, and avoidance of indwelling
neuraxial catheters
Herbal Preparations:
Of concem to the anesthesia provider is the side
effect of bleeding in the patient who consumes
herbal preparations,
Mechanism of action: varies with the preparation.
+ Garlic, ginger, feverfew: inhibit platelet
aggregation
+ Ginseng: antiplatelet components
+ Alfalfa, chamomile, horse chestnut, ginseng
contain a coumadin component
+ Vitamin E: reduces platelet thromboxane
production
+ Ginko: inhibits platelet activating factor
‘The risk for epidural/spinal hematoma is unknown. Surgical
patients should be advised to stop herbal products 5-7 days
before surgery. One of the crucial aspects of preoperative
assessment is the concomitant use medications that alter
‘coagulation. In addition, the patient should be screened for
bleeding tendencies
y
F Coumadin/Warfarin:
+ Chronic oral anticoagulation should be
stopped 4-5 days prior to block, and PT/
INR checked before procedure
performed.
+ If initial dose given >24 hrs prior to
procedure or if 2 or more doses given,
check PT/INR before block.
+ Catheters can be safely maintained on
low dose (5mg) warfarin therapy
CheckPT/INR QD for indwelling catheter
in pts on warfarin
+ If INF > 3, with hold or reduce coumadin
dose,
+ Catheters can be removed when INR <
15.
+ Minimize local anesthetic concentration;
monitor neuro status during therapy and
for 24hrs after catheter removal
Dr Azam's Notes in Anesthesiology 2013
[CAnti-platelet Medications
+ Includes NSAIDS
(motrin naproxen) thienopyridines(ticlopidine
and clopidogrel), glycoprotein Ilb/lla
antagonists (abciximab, tirofiban)
+ Bleeding time not a reliable test. Risk for
bleeding increased in females, elderly, and
those with a history of easy bruising/
excessive bleeding.
+ NSAIDS-no added risk or timing concems
for neuraxial techniques when used alone.
Ticlopidine,clopidogrel, and platelet GP
antagonist may represent significant risk:
+ Tielopidine- discontinue 14 days prior to
block Clopidogrel- discontinue 7 days prior
to block
+ Abciximab- discontinue 2 days prior
+ Eptifibatide and tirofiban- discontinue Bhrs
prior to block (GPlIbAlla)
Cox-2selective inhibitors(rofecoxib, celecoxib,
valdecoxib)
+ Minimal effect of platelet function.
+ Consider in patients requiring anti-
inflammatory peri-operatively.
A Dr Azam’s Notes in Anesthesiology 2013
F Fondaparinux
+ Anti-thrombotic effect through factor Xa
inhibition, actual risk unknown.
+ Consensus recommendations based on the
sustained and irreversible anti thrombotic effect,
early postoperative dosing, and report of spinal
hematoma reported during initial clinical trials,
+ Recommend single needle pass, atraumatic
needle placement, and avoidance of indwelling
neuraxial catheters
Herbal Preparations:
Of concem to the anesthesia provider is the side
effect of bleeding in the patient who consumes
herbal preparations,
Mechanism of action: varies with the preparation.
+ Garlic, ginger, feverfew: inhibit platelet
aggregation
+ Ginseng: antiplatelet components
+ Alfalfa, chamomile, horse chestnut, ginseng
contain a coumadin component
+ Vitamin E: reduces platelet thromboxane
production
+ Ginko: inhibits platelet activating factor
‘The risk for epidural/spinal hematoma is unknown. Surgical
patients should be advised to stop herbal products 5-7 days
before surgery. One of the crucial aspects of preoperative
assessment is the concomitant use medications that alter
‘coagulation. In addition, the patient should be screened for
bleeding tendencies
10. What is Disseminated intravascular coagulation? Enumerate its causes and management.
Disseminated intravascular coagulation (DIC), also known as disseminated intravascular coagulopathy
or consumptive coagulopathy, is a pathological activation of coagulation (blood clotting) mechanisms
that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside
the blood vessels throughout the body
[Tissue destruction
y
[Extrinsic pathway]
intravascular fibrin deposition]
y
[Thrombosis
e
N
A
[Pathophysiology of DIC:
———
[Stimulus]
Y
[Tissue factor
y
[Thrombin generation
y
[Plasminogen activation
Dr Azam’s Notes in Anesthesiology 2013
[Endothelial Injury
RBC's
Damaged
|
[Tissue Ischemia
y
Plasmin generation] > en
Y
Fibrinolysis
y
[Fibrin degradation products (inhibit
thrombin & platelet aggregation)
DE
[Factor XII activation (Intrinsic pathway)
y
[Platelet consumption
N
[Thrombocytopenia
[Decrease 02
ransport
e
[Hemolytic anemia
Dr Azam's Notes in Anesthesiology 2013
[ORGAN FAILURE
[Tissue Hypoxia
ll 20
Disseminated intravascular coagulation (DIC), also known as disseminated intravascular coagulopathy
or consumptive coagulopathy, is a pathological activation of coagulation (blood clotting) mechanisms
that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside
the blood vessels throughout the body
[Tissue destruction
y
[Extrinsic pathway]
intravascular fibrin deposition]
y
[Thrombosis
e
N
A
[Pathophysiology of DIC:
———
[Stimulus]
Y
[Tissue factor
y
[Thrombin generation
y
[Plasminogen activation
Dr Azam’s Notes in Anesthesiology 2013
[Endothelial Injury
RBC's
Damaged
|
[Tissue Ischemia
y
Plasmin generation] > en
Y
Fibrinolysis
y
[Fibrin degradation products (inhibit
thrombin & platelet aggregation)
DE
[Factor XII activation (Intrinsic pathway)
y
[Platelet consumption
N
[Thrombocytopenia
[Decrease 02
ransport
e
[Hemolytic anemia
Dr Azam's Notes in Anesthesiology 2013
[ORGAN FAILURE
[Tissue Hypoxia
ll 20
Clinical Features: S/S
+ Bleeding or bruising - from Gl Tract,
genitourinary tract, ecchymosis petechiae,
purpura.
+ Laboratory findings: Thrombocytopenia,
anemia, prolonged PT aPTT & FDP,
Deranged D-DIMER,
Investigation: Abnormalities of Lab DIC:
+ Increase PT, aPTT
+ Decrease platelets
+ Smear = Schitocytes
+ Decrease in Fibrinogen
+ Decrease in Factor V
+ Decrease in Factor VIII
+ Increase in D-DIMER
Dr Azam’s Notes in Anesthesiology 2013
[Enumerate Its causes and management. Continuation: Dr Azant's Notes in Anesthesiology 2013
[Causes
for DIC
Infection: [Obstetric: (Malignancy: Traumatic: [intravascular Hemolysis:
| Septicemia | |: Pre-Eclampsia | Acute promyelocytic | |: Polytrauma with shock | |. snake Venom
| Viremia | Placental abruption leukemia |} Bums |. ABO transfusion reaction
| Fungaemia | |. Amniotic fluid embolism | |. Metastatic carcinoma | |. Fat embolism
| Protozal |. Retained products of [+ Neurosurgery
conception
| Placenta praevia
‘Treatment & Management of DIC:
- Treat the underlying cause
+ Provide supportive management of complications
+ Support organ function
+ Stop abnormal coagulation and control bleeding by replacement of depleted blood and
clotting components (FFP Platelets,PRBC)
+ Medications can be used and choice depends on the patient's condition (Heparin,
Antithrombin III (ATIII), Fibrinolytic inhibitors)
Plasma therapy
Indications
+ Active bleeding
+ Patient requiring invasive procedures
+ Patient at high risk for bleeding complications
Fresh frozen plasma(FFP):
- Provides clotting factors, fibrinogen, inhibitors, and platelets in balanced amounts.
- Usual dose is 10-15 ml/kg
Platelet Therapy:
Indications
+ Active bleeding
+ Patient requiring invasive procedures
- Patient at high risk for bleeding complications
+ Platelets
+ approximate dose 1 unit/10kg
+ Cryoprecipitate = 1U/10 kg
- Fibrinogen concentrate = 2 - 3 gms at
+ Bleeding or bruising - from Gl Tract,
genitourinary tract, ecchymosis petechiae,
purpura.
+ Laboratory findings: Thrombocytopenia,
anemia, prolonged PT aPTT & FDP,
Deranged D-DIMER,
Investigation: Abnormalities of Lab DIC:
+ Increase PT, aPTT
+ Decrease platelets
+ Smear = Schitocytes
+ Decrease in Fibrinogen
+ Decrease in Factor V
+ Decrease in Factor VIII
+ Increase in D-DIMER
Dr Azam’s Notes in Anesthesiology 2013
[Enumerate Its causes and management. Continuation: Dr Azant's Notes in Anesthesiology 2013
[Causes
for DIC
Infection: [Obstetric: (Malignancy: Traumatic: [intravascular Hemolysis:
| Septicemia | |: Pre-Eclampsia | Acute promyelocytic | |: Polytrauma with shock | |. snake Venom
| Viremia | Placental abruption leukemia |} Bums |. ABO transfusion reaction
| Fungaemia | |. Amniotic fluid embolism | |. Metastatic carcinoma | |. Fat embolism
| Protozal |. Retained products of [+ Neurosurgery
conception
| Placenta praevia
‘Treatment & Management of DIC:
- Treat the underlying cause
+ Provide supportive management of complications
+ Support organ function
+ Stop abnormal coagulation and control bleeding by replacement of depleted blood and
clotting components (FFP Platelets,PRBC)
+ Medications can be used and choice depends on the patient's condition (Heparin,
Antithrombin III (ATIII), Fibrinolytic inhibitors)
Plasma therapy
Indications
+ Active bleeding
+ Patient requiring invasive procedures
+ Patient at high risk for bleeding complications
Fresh frozen plasma(FFP):
- Provides clotting factors, fibrinogen, inhibitors, and platelets in balanced amounts.
- Usual dose is 10-15 ml/kg
Platelet Therapy:
Indications
+ Active bleeding
+ Patient requiring invasive procedures
- Patient at high risk for bleeding complications
+ Platelets
+ approximate dose 1 unit/10kg
+ Cryoprecipitate = 1U/10 kg
- Fibrinogen concentrate = 2 - 3 gms at
[Enumerate its causes and management of DIC. Continuation:
‘Treatment & Management of DIC:
Blood Therapy:
+ Replaced as needed to maintain adequate oxygen delivery.
+ Blood loss due to bleeding
+ RBC destruction (hemolysis)
Coagulation Therapy:
+ Antithrombin Ii
+ Protein C concentrate
+ Tissue Factor Pathway Inhibitor (TFPI)
+ Heparin
Antithrombin Ill:
+ The major inhibitor of the coagulation cascade
+ Levels are decreased in DIC.
+ Anticoagulant and anti-inflammatory properties
+ Therapeutic goal is to achieve supranormal levels of ATIII
(>125-150%)
Recombinant Protein C:
+ Inhibits Factor Va, Vila and PAI-1 in conjunction with
thrombomodulin.
+ Protein Sis a cofactor
Preoperative preparation:
+ Antibiotics for infection
+ Hypovolemia to be corrected
+ Warm fluids & Blood products
+ Evacuation of retained products of conception
+ Blood product to given based on the laboratory
investigations
- Coagulopathy corrected with FFP & platelets
- If fibrinogen level < 1gmsfiter - Cryoprecipitate to be
transfused
+ Adequate blood & blood products to be available before
surgery
+ Recombinant protein C - in severe sepsis
+ Intra-muscular injections to be avoided
Dr Azam's Notes in Anesthesiology 2013
Dr Azam’s Notes in Anesthesiology 2013
Perl-operative Anesthetic implications & Management:
+ Coagulopathy - CI for regional anesthesia
+ General anesthesia is preferred
+ Invasive cardiovascular monitoring required - ABP,CVP
+ Large bore IV lines for rapid transfusion
+ Naso-tracheal intubation to be avoided
+ Blood, platelet concentrate, FFP & Cryoprecipitate should
be transfused promptly, bleeding parameters needs to be
measured regularly
Post-operative management:
+ Patients to be managed in ICU
+ May require mechanical ventilation
+ Hypothermia to be avoided
+ Antibiotics to be continued
+ Frequent measurement of PT,PTT & INR to be done.
Note:
+ Epsilon Amino Caproic Acid and fibrinogen should not be
administered in presence of continuing intravascular
coagulation. EACA would inhibit secondary fibrinolysis
Which is an intrinsic protective mechanism in patients with
persistent DIC.
32
‘Treatment & Management of DIC:
Blood Therapy:
+ Replaced as needed to maintain adequate oxygen delivery.
+ Blood loss due to bleeding
+ RBC destruction (hemolysis)
Coagulation Therapy:
+ Antithrombin Ii
+ Protein C concentrate
+ Tissue Factor Pathway Inhibitor (TFPI)
+ Heparin
Antithrombin Ill:
+ The major inhibitor of the coagulation cascade
+ Levels are decreased in DIC.
+ Anticoagulant and anti-inflammatory properties
+ Therapeutic goal is to achieve supranormal levels of ATIII
(>125-150%)
Recombinant Protein C:
+ Inhibits Factor Va, Vila and PAI-1 in conjunction with
thrombomodulin.
+ Protein Sis a cofactor
Preoperative preparation:
+ Antibiotics for infection
+ Hypovolemia to be corrected
+ Warm fluids & Blood products
+ Evacuation of retained products of conception
+ Blood product to given based on the laboratory
investigations
- Coagulopathy corrected with FFP & platelets
- If fibrinogen level < 1gmsfiter - Cryoprecipitate to be
transfused
+ Adequate blood & blood products to be available before
surgery
+ Recombinant protein C - in severe sepsis
+ Intra-muscular injections to be avoided
Dr Azam's Notes in Anesthesiology 2013
Dr Azam’s Notes in Anesthesiology 2013
Perl-operative Anesthetic implications & Management:
+ Coagulopathy - CI for regional anesthesia
+ General anesthesia is preferred
+ Invasive cardiovascular monitoring required - ABP,CVP
+ Large bore IV lines for rapid transfusion
+ Naso-tracheal intubation to be avoided
+ Blood, platelet concentrate, FFP & Cryoprecipitate should
be transfused promptly, bleeding parameters needs to be
measured regularly
Post-operative management:
+ Patients to be managed in ICU
+ May require mechanical ventilation
+ Hypothermia to be avoided
+ Antibiotics to be continued
+ Frequent measurement of PT,PTT & INR to be done.
Note:
+ Epsilon Amino Caproic Acid and fibrinogen should not be
administered in presence of continuing intravascular
coagulation. EACA would inhibit secondary fibrinolysis
Which is an intrinsic protective mechanism in patients with
persistent DIC.
32
Dr Azam’s Notes in Anesthesiology 2013
& cryoprecipitates.
[T1. Enumerate the indications of packed red cells, fresh frozen plasma(FFP), platelets
A. Packed Red Cells:
Indications of Packed red cell:
+ Deficient oxygen caring capacity or tissue hypoxia, due to
inadequate circulating red cell mass
+ Exchange transfusion in hemolytic disease of new bom or
in Sickle cell anemia
+ Hypovolemia secondary to hemorthagic shock
Description of Packed red cells:
+ 150 to 200 mi red cells from which most of the plasma has
been removed
+ Hemoglobin approximately 20 g/100 ml (not less that 45 g/
unit)
+ Hematocrit 55 to 75%.
B. Fresh Frozen Plasma:
Indications of FFP's:
+ Congenital factor deficiency
+ Invasive procedure or trauma { e.g. factor XI deficiency)
+ Emergency warfarin reversal
+ Acquired bleeding disorders with active bleeding or prior to
an invasive procedure. (liver disease; vitamin K deficiency;
disseminated intravascular coagulation; dilutional
coagulopathy).
+ Microvascular bleeding & elevated PT/PTT
+ Loss of more that one blood volume & no lab values then
give empirically
+ FFP is indicated in massive transfusion with demonstrated
deficiency of factor VIII & V
+ Exchange transfusion in neonates.
Dr Azam's Notes in Anesthesiology 2013
FFP's Continued:
Product
+ Anticoagulated plasma in frozen state
Characteristics
Volume: 200-250 mi (= 1 unit)
Contains all plasma proteins
Pharmacological Effect
Increase plasma clotting factors and prevent or stop
bleeding
Dose of FFP:
10-15 mg
C. Cryoprecipitate:
Definition: IT IS THE INSOLUBLE PORTION OF PLASMA REMAINING AFTER THE FRESH
FROZEN PLASMA HAS BEEN THAWED BETWEEN 4°C TO 6°C. Increase plasma levels
of high molecular weight clotting factors
Indications of Cryoprecipitate:
+ Hemophilia A
+ Von Willebrand's disease
+ Congenital or acquired fibrinogen deficiency
+ DIC
+ Massive transfusion with dilutional hypofibrinogenemia
+ Hypofibrinogenemia: Fibrinogen < 100 mg/dl. with active bleeding or fibrinogen
< 200 mg/dL in a postoperative patient with excessive bleeding.
+ Uremia or hereditary platelet disorder
+ Factor XIII Deficiency
Composition:
+ Volume: 5 - 15 ml (= 1 Unit; 1 BAG)
+ Contains high molecular weight glycoproteins such as fibrinogen (300 mg/unit);
Factor VIII (80-100 Umit); von Willebrand factor; factor XIII
Dose:
+L uni/10 Kg wt; Frequently 10 BAGS $
& cryoprecipitates.
[T1. Enumerate the indications of packed red cells, fresh frozen plasma(FFP), platelets
A. Packed Red Cells:
Indications of Packed red cell:
+ Deficient oxygen caring capacity or tissue hypoxia, due to
inadequate circulating red cell mass
+ Exchange transfusion in hemolytic disease of new bom or
in Sickle cell anemia
+ Hypovolemia secondary to hemorthagic shock
Description of Packed red cells:
+ 150 to 200 mi red cells from which most of the plasma has
been removed
+ Hemoglobin approximately 20 g/100 ml (not less that 45 g/
unit)
+ Hematocrit 55 to 75%.
B. Fresh Frozen Plasma:
Indications of FFP's:
+ Congenital factor deficiency
+ Invasive procedure or trauma { e.g. factor XI deficiency)
+ Emergency warfarin reversal
+ Acquired bleeding disorders with active bleeding or prior to
an invasive procedure. (liver disease; vitamin K deficiency;
disseminated intravascular coagulation; dilutional
coagulopathy).
+ Microvascular bleeding & elevated PT/PTT
+ Loss of more that one blood volume & no lab values then
give empirically
+ FFP is indicated in massive transfusion with demonstrated
deficiency of factor VIII & V
+ Exchange transfusion in neonates.
Dr Azam's Notes in Anesthesiology 2013
FFP's Continued:
Product
+ Anticoagulated plasma in frozen state
Characteristics
Volume: 200-250 mi (= 1 unit)
Contains all plasma proteins
Pharmacological Effect
Increase plasma clotting factors and prevent or stop
bleeding
Dose of FFP:
10-15 mg
C. Cryoprecipitate:
Definition: IT IS THE INSOLUBLE PORTION OF PLASMA REMAINING AFTER THE FRESH
FROZEN PLASMA HAS BEEN THAWED BETWEEN 4°C TO 6°C. Increase plasma levels
of high molecular weight clotting factors
Indications of Cryoprecipitate:
+ Hemophilia A
+ Von Willebrand's disease
+ Congenital or acquired fibrinogen deficiency
+ DIC
+ Massive transfusion with dilutional hypofibrinogenemia
+ Hypofibrinogenemia: Fibrinogen < 100 mg/dl. with active bleeding or fibrinogen
< 200 mg/dL in a postoperative patient with excessive bleeding.
+ Uremia or hereditary platelet disorder
+ Factor XIII Deficiency
Composition:
+ Volume: 5 - 15 ml (= 1 Unit; 1 BAG)
+ Contains high molecular weight glycoproteins such as fibrinogen (300 mg/unit);
Factor VIII (80-100 Umit); von Willebrand factor; factor XIII
Dose:
+L uni/10 Kg wt; Frequently 10 BAGS $
[Enumerate the indications of packed red cells, fresh frozen plasma(FFP),
platelets & cryoprecipitates. Continuation:
D. Platelets:
Indications of Platelets:
+ Thrombocytopenia
+ Platelet function defect
+ Microvascular bleeding in surgical or obstetric patients
+ Dengue fever
+ Massive blood transfusion
Characteristics:
‘Whole Blood Apheresis
Donation Donation
Potency 5-8x 1010 40x 1010
Volume (ml) 35-60 180 - 400
Labeling Platelets Platelets, pheresis
Common Usage | Random Donor | Single Donor Unit
Units
Platelets increased by | 5000 - 7000 60,000 to 70,000
Doses of Platelets:
+ 1 uni/10 Kg weight; 4 units/m2 Surface Area
+ 1 Platelets, Apheresis
Dr Azam's Notes in Anesthesiology 2013
Dr Azam’s Notes in Anesthesiology 2013
platelets & cryoprecipitates. Continuation:
D. Platelets:
Indications of Platelets:
+ Thrombocytopenia
+ Platelet function defect
+ Microvascular bleeding in surgical or obstetric patients
+ Dengue fever
+ Massive blood transfusion
Characteristics:
‘Whole Blood Apheresis
Donation Donation
Potency 5-8x 1010 40x 1010
Volume (ml) 35-60 180 - 400
Labeling Platelets Platelets, pheresis
Common Usage | Random Donor | Single Donor Unit
Units
Platelets increased by | 5000 - 7000 60,000 to 70,000
Doses of Platelets:
+ 1 uni/10 Kg weight; 4 units/m2 Surface Area
+ 1 Platelets, Apheresis
Dr Azam's Notes in Anesthesiology 2013
Dr Azam’s Notes in Anesthesiology 2013
F2. Write the blood conservative strategies In a 20 year old female scheduled Dr Azam's Notes in Anesthesiology 2013
for excision of anglofibroma of nose?
Blood conservative strategies are getting great clinical relevance due to + Surgical hemostasis is done using bone wax & surgicel
the concem in transfusion allogenic blood. This is done to avoid + Local hemostatic agents such as: fibrin spray, application of
potential risk associated with blood transfusion. platelet gel before wound closure, topical use of Tranexemic
acid
Methods of reducing blood transfusion/Method for blood + Systemic hemostatic agents Tranexemic acid,
conservation strategies are: desmopressin, aprotinin
+ Tranexemic acid ( synthetic fibrinolytic inhibitor) reduces
1. Optimization of the preoperative hemoglobin: bleeding
+ Preoperative Hb is best predictor of the need for allogenic transfusion + Initial bolus dose 10 mg/kg Max of 30 mg/kg/day
+ If Anemia due to Iron deficiency - oral iron is prescribed, If it is not + Pneumatic toumiquet
effective intravenous administration of iron-sucrose can be done,
+ If anemia not due to iron or Vit B12 deficiency or absence of chronic 3. Lowering the transfusion trigger:
blood loss then Hb & HOT will improve with administration of + The transfusion trigger of 10gmiil & HCT of 30% can be safely
erythropoietin combined with iron supplement. be lowered in most patients without any cardia or respiratory
+ Erythropoletin Regimen: co-morbidities.
+ 300U/kg for 15 days beginning 10 days before surgery or + 8 gmidl in older without any co-morbidity & 7 gmédl in younger
+ Weekly administration of 600 U/kg starting 3 weeks before surgery healthy patients
+ Erythropoietin should always be combined with iron
supplementation. 4, Strategies in optimization of use of patients own blood:
Can be done by
2. Strategies to decrease perioperative blood loss / Reduction of + Acute isovolemic hemodilution: blood has low HOT which
blood loss: reduces RBC loss. It enhances microcirculation
+ Any congenital or acquired bleeding disorders should be detected + Autologus blood donation & transfusion: It should be targeted
+ Aspirin & NSAIDS to be stopped 1 week before surgery to men with Hb of 11 to 14 gmidl & to women with level of 13 to
Patients of LMWH, Vit K antagonist & aspirin should be stopped 14.gmidl, whose blood loss is close to 1000 ml
before surgery. + Perioperative blood salvage’
+ Position of the patient affects intraoperative bleeding: + Re-infusion of blood drained within 6 hours after operation
+ Lateral position in THR decreases blood loss using cell salvage.
+ Elevation of lower limbs after TKR reduces post operative blood + Itis generally accepted that no more than 1000 ml of
loss drained blood be re-infused & not more than 6 hours after
+ Controlled hypotensive spinal or epidural anesthesia using adjuvants end of surgery should not be transfused.
like clonidine neuraxially decreases blood loss + Contraindicated in patients with infection & malignancy.
+ Maintaining normothermia decreases bleeding.
+ Preoperative arterial embolization for complex pelvic fractures or
highly vascular tumors 5
Dr Azam's Notes in Anesthesiology 2013
for excision of anglofibroma of nose?
Blood conservative strategies are getting great clinical relevance due to + Surgical hemostasis is done using bone wax & surgicel
the concem in transfusion allogenic blood. This is done to avoid + Local hemostatic agents such as: fibrin spray, application of
potential risk associated with blood transfusion. platelet gel before wound closure, topical use of Tranexemic
acid
Methods of reducing blood transfusion/Method for blood + Systemic hemostatic agents Tranexemic acid,
conservation strategies are: desmopressin, aprotinin
+ Tranexemic acid ( synthetic fibrinolytic inhibitor) reduces
1. Optimization of the preoperative hemoglobin: bleeding
+ Preoperative Hb is best predictor of the need for allogenic transfusion + Initial bolus dose 10 mg/kg Max of 30 mg/kg/day
+ If Anemia due to Iron deficiency - oral iron is prescribed, If it is not + Pneumatic toumiquet
effective intravenous administration of iron-sucrose can be done,
+ If anemia not due to iron or Vit B12 deficiency or absence of chronic 3. Lowering the transfusion trigger:
blood loss then Hb & HOT will improve with administration of + The transfusion trigger of 10gmiil & HCT of 30% can be safely
erythropoietin combined with iron supplement. be lowered in most patients without any cardia or respiratory
+ Erythropoletin Regimen: co-morbidities.
+ 300U/kg for 15 days beginning 10 days before surgery or + 8 gmidl in older without any co-morbidity & 7 gmédl in younger
+ Weekly administration of 600 U/kg starting 3 weeks before surgery healthy patients
+ Erythropoietin should always be combined with iron
supplementation. 4, Strategies in optimization of use of patients own blood:
Can be done by
2. Strategies to decrease perioperative blood loss / Reduction of + Acute isovolemic hemodilution: blood has low HOT which
blood loss: reduces RBC loss. It enhances microcirculation
+ Any congenital or acquired bleeding disorders should be detected + Autologus blood donation & transfusion: It should be targeted
+ Aspirin & NSAIDS to be stopped 1 week before surgery to men with Hb of 11 to 14 gmidl & to women with level of 13 to
Patients of LMWH, Vit K antagonist & aspirin should be stopped 14.gmidl, whose blood loss is close to 1000 ml
before surgery. + Perioperative blood salvage’
+ Position of the patient affects intraoperative bleeding: + Re-infusion of blood drained within 6 hours after operation
+ Lateral position in THR decreases blood loss using cell salvage.
+ Elevation of lower limbs after TKR reduces post operative blood + Itis generally accepted that no more than 1000 ml of
loss drained blood be re-infused & not more than 6 hours after
+ Controlled hypotensive spinal or epidural anesthesia using adjuvants end of surgery should not be transfused.
like clonidine neuraxially decreases blood loss + Contraindicated in patients with infection & malignancy.
+ Maintaining normothermia decreases bleeding.
+ Preoperative arterial embolization for complex pelvic fractures or
highly vascular tumors 5
Dr Azam's Notes in Anesthesiology 2013
lot nose? Continuation:
[Write the blood conservative strategies in a 20 year old female scheduled for excision of angiofibroma]
Dr Azam’s Notes in Anesthesiology 2013
[Use of Blood Substitutes: Two types
lot blood substitutes are available:
Perflurocarbons:
+ They are biologically inert volatile fluids
with high dissolving capacity for 02 & CO2
+ They transport & deliver O2 by simple
physical dissolution
+ Not water soluble
+ their O2 carrying capacity depends on the
concentration of perflurocarbons which
varies between products.
+ H+ atoms are replaced by fluorines
+ One unit of perflurocarbons carry 3
times O2 carried by similar volume of
blood
+ Fluosol - DA : 20 % emulsion of 2
different compounds. Dose = 20ml/kg
+ Polyfluro-octobromide: O2 solubility is
more
Dr Azam's Notes in Anesthesiology 2013
\
Hb based 02 carriers:
+ These are based on natural or
recombinant human Hb or bovine Hb
+ produced by purification, encapsulation in
synthetic phospholid
+ Side effect
+ Increased Blood pressure due to
increased systemic vasoconstriction
due to scavenging of nitric oxide &
oxidation which generated Meth Hb.
+ Short intravascular halflife
+ hence used in emergency situation
[Write the blood conservative strategies in a 20 year old female scheduled for excision of angiofibroma]
Dr Azam’s Notes in Anesthesiology 2013
[Use of Blood Substitutes: Two types
lot blood substitutes are available:
Perflurocarbons:
+ They are biologically inert volatile fluids
with high dissolving capacity for 02 & CO2
+ They transport & deliver O2 by simple
physical dissolution
+ Not water soluble
+ their O2 carrying capacity depends on the
concentration of perflurocarbons which
varies between products.
+ H+ atoms are replaced by fluorines
+ One unit of perflurocarbons carry 3
times O2 carried by similar volume of
blood
+ Fluosol - DA : 20 % emulsion of 2
different compounds. Dose = 20ml/kg
+ Polyfluro-octobromide: O2 solubility is
more
Dr Azam's Notes in Anesthesiology 2013
\
Hb based 02 carriers:
+ These are based on natural or
recombinant human Hb or bovine Hb
+ produced by purification, encapsulation in
synthetic phospholid
+ Side effect
+ Increased Blood pressure due to
increased systemic vasoconstriction
due to scavenging of nitric oxide &
oxidation which generated Meth Hb.
+ Short intravascular halflife
+ hence used in emergency situation
13. Autologus Blood transfusion.
Definition: Autologous blood transfusion is one in
which both donor as well as recipient are the same.
Types of autologous blood transfusion:
I. Preoperative blood donation
Il. Intraoperative blood salvage
lll. Postoperative blood salvage
IV. Isovolemic hemodilution
|. PREOPERATIVE BLOOD DONATION:
Criteria:
+ The haemoglobin > T1gmadl
+ The haemoglobin never below 10gm/dl
Contraindication:
+ Active bacterial infection
+ Cardiac disease
+ Loss of consciousness
+ Impaired placental blood flow — HTN, PET, DM
+ COPD - Emphysema
Method:
+ 450ml of blood at weekly intervals.
+ Last donation 4 days before surgery
- Preferably 1 week prior to surgery.
+ Should commence oral iron prior to their first
donation and continue until the day of surgery.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Il. INTRAOPERATIVE BLOOD SALVAGE:
+ Pre-deposit donation is limited by the time that the blood can be
stored and by the ability of patients to donate at frequent intervals.
The main steps of this technique are
1. Salvaging the blood from the operative site.
2. Anticoagulating the whole blood — prior to surgery and during
‘suction.
3. Re-infusing whole blood as such after filtering or re-infusing the
red cells after washing,
There are three basic methods for IBS:
1. Semi continuous flow centrifugation
2. Canister collection
3. Single use disposable reservoirs
1. Semi continuous flow centrifugation:
+ Blood is aspirated, using a double lumen sucker, into a reservoir.
+ The blood is washed, with saline prior to being re-infused.
+ Two varieties of equipment available, the so called
+ slow flow machines which produce one unit every 7-10 mins
- Fast flow system which produce a unit in less than 3 mins.
2) Canister collection:
+ Aspirated, via a double lumen sucker
+ Allows anticoagulant to be mixed at the sucker tip, through a
170, filter into a rigid reservoir containing a disposable liner.
37
Definition: Autologous blood transfusion is one in
which both donor as well as recipient are the same.
Types of autologous blood transfusion:
I. Preoperative blood donation
Il. Intraoperative blood salvage
lll. Postoperative blood salvage
IV. Isovolemic hemodilution
|. PREOPERATIVE BLOOD DONATION:
Criteria:
+ The haemoglobin > T1gmadl
+ The haemoglobin never below 10gm/dl
Contraindication:
+ Active bacterial infection
+ Cardiac disease
+ Loss of consciousness
+ Impaired placental blood flow — HTN, PET, DM
+ COPD - Emphysema
Method:
+ 450ml of blood at weekly intervals.
+ Last donation 4 days before surgery
- Preferably 1 week prior to surgery.
+ Should commence oral iron prior to their first
donation and continue until the day of surgery.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Il. INTRAOPERATIVE BLOOD SALVAGE:
+ Pre-deposit donation is limited by the time that the blood can be
stored and by the ability of patients to donate at frequent intervals.
The main steps of this technique are
1. Salvaging the blood from the operative site.
2. Anticoagulating the whole blood — prior to surgery and during
‘suction.
3. Re-infusing whole blood as such after filtering or re-infusing the
red cells after washing,
There are three basic methods for IBS:
1. Semi continuous flow centrifugation
2. Canister collection
3. Single use disposable reservoirs
1. Semi continuous flow centrifugation:
+ Blood is aspirated, using a double lumen sucker, into a reservoir.
+ The blood is washed, with saline prior to being re-infused.
+ Two varieties of equipment available, the so called
+ slow flow machines which produce one unit every 7-10 mins
- Fast flow system which produce a unit in less than 3 mins.
2) Canister collection:
+ Aspirated, via a double lumen sucker
+ Allows anticoagulant to be mixed at the sucker tip, through a
170, filter into a rigid reservoir containing a disposable liner.
37
[Autologus Blood transfusion. Continuation:
1) Single use Disposable reservoirs:
+ Blood is aspirated using a vacuum pressure of less than
150mm Hg
+ Anticoagulated prior to surgery,
+ Anticoagulated using citrate.
+ Re-infused by gravity using microaggregate filter,
+ stored until room temperature, until required.
Advantage — cheap and requiring no specialized
equipment or specially trained personnel
Disadvantage — slow, small volumes, unwashed and has
a low hematocrit.
Precautions:
Avoid hemolysis:
+ The sucker should have a plastic tip with multiple holes
+ Turbulence to be avoided
+ pressure to be below 150-200 mmHg.
Anticoagulants:
+ Citrate in a ratio of 1:5 to 1:1, or heparin at a concentration
of 30,000 units per It of saline, with 15ml of heparin /
saline being added to each 100 ml of blood (ratio heparin
to blood, 1:7).
Wash solution:
+ The volume of saline wash solution should be three to four
times that of the volume of the blood, although for
orthopedic cases this may be increased to six to seven
times with a minimum volume of 150ml.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
INDICATIONS FOR INTRAOPERATIVE CELL SALVAGE:
+ Cardiovascular:
+ Vascular surgery:
- Aortic aneurysm
= Aortic rupture
+ Orthopedic: Hip and spinal surgery
+ Liver transplantation
+ Neurosurgery
+ Trauma
+ Plastic surgery
+ Jehovah's witnesses
+ Serological antibodies:
Contraindications:
+ Infections, sepsis, bacteremia
+ Blood containing significant amounts of amniotic fluid
should not be auto transfused.
+ Blood containing:
+ wound irrigants Betadine;
+ methyimethacrylate,
+ antibiotics
1) Single use Disposable reservoirs:
+ Blood is aspirated using a vacuum pressure of less than
150mm Hg
+ Anticoagulated prior to surgery,
+ Anticoagulated using citrate.
+ Re-infused by gravity using microaggregate filter,
+ stored until room temperature, until required.
Advantage — cheap and requiring no specialized
equipment or specially trained personnel
Disadvantage — slow, small volumes, unwashed and has
a low hematocrit.
Precautions:
Avoid hemolysis:
+ The sucker should have a plastic tip with multiple holes
+ Turbulence to be avoided
+ pressure to be below 150-200 mmHg.
Anticoagulants:
+ Citrate in a ratio of 1:5 to 1:1, or heparin at a concentration
of 30,000 units per It of saline, with 15ml of heparin /
saline being added to each 100 ml of blood (ratio heparin
to blood, 1:7).
Wash solution:
+ The volume of saline wash solution should be three to four
times that of the volume of the blood, although for
orthopedic cases this may be increased to six to seven
times with a minimum volume of 150ml.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
INDICATIONS FOR INTRAOPERATIVE CELL SALVAGE:
+ Cardiovascular:
+ Vascular surgery:
- Aortic aneurysm
= Aortic rupture
+ Orthopedic: Hip and spinal surgery
+ Liver transplantation
+ Neurosurgery
+ Trauma
+ Plastic surgery
+ Jehovah's witnesses
+ Serological antibodies:
Contraindications:
+ Infections, sepsis, bacteremia
+ Blood containing significant amounts of amniotic fluid
should not be auto transfused.
+ Blood containing:
+ wound irrigants Betadine;
+ methyimethacrylate,
+ antibiotics
[Autologus Blood transfusion. Continuation:
COMPLICATIONS FOR INTRAOPERATIVE CELL SALVAGE:
1) Air embolism
2) Re-infusion of hemolyzed red cells:
If the vacuum pressure on the sucker is too high or
excess turbulence has been caused by improper
aspiration technique, hemolyzed red cells can be re-
infused into the patient
3) Coagulation disorders
4) Thrombocytopenia
5) Hypocalcaemia
7) Toxic antibiotic effects
8) Microfibrillar collagen haemostatic material
Ill. Post operative blood Salvage:
Used in:
+ CTVS
+ Joint replacement
+ Trauma - chest wall & abdomen
+ Vacuum pressure = 0 - 40 mm of Hg
+ Time between start of collection & re-infusion should be
< 4 hours.
Product has:
+ No clotting factors
+ HOT 15- 20%
+ Free Hb
Complication:
+ Products of clot lysis Volume > 800 mi of unwashed
blood are re-infused.
+ Upper airway oedema requiring intubation
+ Non-cardiogenic pulmonary oedema
Dr Azanvs Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
IV, ACUTE NORMOVOLAEMIC HEMODILUTIONAsovolemic:
+ Definition: It indicates dilution of the blood while keeping the circulating
blood volume constant.
+ HOT is used
Contraindications to acute normovolaemic hemodilution:
1. Hematocrit less than 24%,
2. Valvular heart disease and intra or extra cardiac shunting
3. Respiratory insufficiency needing mechanical ventilation.
4. Haemostatic defects.
Compensatory mechanisms during hemodilution:
- Blood Rheology: Decreased viscosity 8 decreased oxygen carrying
capacity
+ Utilization of O2:
+ Increased blood flow to the tissue
+ Increased oxygen extraction
+ Autonomic effects
Effect on organ systems:
1) Cardiac: Increased CO, Increased Coronary blood flow, Coronary
Vasodilation.
li) Cerebral: Increased Cerebral blood flow
ill) Hepatic and gastrointestinal: Increased Hepatic blood flow,
Increased oxygen extraction
Iv) Renal: Decreases renal blood flow
v) Pulmonary: Hemodilution does not alter pulmonary function
vi) Pregnancy: Hemodilution should be used with caution in pregnant
patients, may result inadequate oxygen content in the blood perfusing the
placenta.
COMPLICATIONS FOR INTRAOPERATIVE CELL SALVAGE:
1) Air embolism
2) Re-infusion of hemolyzed red cells:
If the vacuum pressure on the sucker is too high or
excess turbulence has been caused by improper
aspiration technique, hemolyzed red cells can be re-
infused into the patient
3) Coagulation disorders
4) Thrombocytopenia
5) Hypocalcaemia
7) Toxic antibiotic effects
8) Microfibrillar collagen haemostatic material
Ill. Post operative blood Salvage:
Used in:
+ CTVS
+ Joint replacement
+ Trauma - chest wall & abdomen
+ Vacuum pressure = 0 - 40 mm of Hg
+ Time between start of collection & re-infusion should be
< 4 hours.
Product has:
+ No clotting factors
+ HOT 15- 20%
+ Free Hb
Complication:
+ Products of clot lysis Volume > 800 mi of unwashed
blood are re-infused.
+ Upper airway oedema requiring intubation
+ Non-cardiogenic pulmonary oedema
Dr Azanvs Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
IV, ACUTE NORMOVOLAEMIC HEMODILUTIONAsovolemic:
+ Definition: It indicates dilution of the blood while keeping the circulating
blood volume constant.
+ HOT is used
Contraindications to acute normovolaemic hemodilution:
1. Hematocrit less than 24%,
2. Valvular heart disease and intra or extra cardiac shunting
3. Respiratory insufficiency needing mechanical ventilation.
4. Haemostatic defects.
Compensatory mechanisms during hemodilution:
- Blood Rheology: Decreased viscosity 8 decreased oxygen carrying
capacity
+ Utilization of O2:
+ Increased blood flow to the tissue
+ Increased oxygen extraction
+ Autonomic effects
Effect on organ systems:
1) Cardiac: Increased CO, Increased Coronary blood flow, Coronary
Vasodilation.
li) Cerebral: Increased Cerebral blood flow
ill) Hepatic and gastrointestinal: Increased Hepatic blood flow,
Increased oxygen extraction
Iv) Renal: Decreases renal blood flow
v) Pulmonary: Hemodilution does not alter pulmonary function
vi) Pregnancy: Hemodilution should be used with caution in pregnant
patients, may result inadequate oxygen content in the blood perfusing the
placenta.
[Autologus Blood transfusion. Continuation:
Methods:
+ Crystalloids: 3:1 crystalloids to blood ratio.
+ Colloids: 1: 1 Colloid to blood ratio.
+ Albumin
+ Dextran
+ Hetastarch
+ Gelatin
Technique:
+ Draw blood either
+ Under anesthesia
+ Prior to induction
+ Blood withdrawal rate must parallel the
administration of appropriate diluent
volumes to assure normovolaemic and
circulatory stability.
+ Serial HOT
+ Collections in bags & bottles
+ Monitoring
Methods:
+ Ferrarie Method:
+ Preoperatively collect:
+ 1-3 U of RBC suspended in saline
together with an average of 1.6 x 10
Platelets & 460 mi of plasma collected
preoperatively.
Takaon’s Method:
+ If Blood loss > 400 ml, 500 ml of RLis
given, after which 600 mi of blood is
withdrawn, which is replaced by 600 mi of
dextran 70.
+ If Blood loss > 1L 600 mi of blood is taken
& is replaced with equal volumes of 600
mi dextran 70.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Methods:
+ Crystalloids: 3:1 crystalloids to blood ratio.
+ Colloids: 1: 1 Colloid to blood ratio.
+ Albumin
+ Dextran
+ Hetastarch
+ Gelatin
Technique:
+ Draw blood either
+ Under anesthesia
+ Prior to induction
+ Blood withdrawal rate must parallel the
administration of appropriate diluent
volumes to assure normovolaemic and
circulatory stability.
+ Serial HOT
+ Collections in bags & bottles
+ Monitoring
Methods:
+ Ferrarie Method:
+ Preoperatively collect:
+ 1-3 U of RBC suspended in saline
together with an average of 1.6 x 10
Platelets & 460 mi of plasma collected
preoperatively.
Takaon’s Method:
+ If Blood loss > 400 ml, 500 ml of RLis
given, after which 600 mi of blood is
withdrawn, which is replaced by 600 mi of
dextran 70.
+ If Blood loss > 1L 600 mi of blood is taken
& is replaced with equal volumes of 600
mi dextran 70.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
14. Replacement therapy for coagulation factor deficiency Dr Azam's Notes in Anesthesiology 2013
actor jerapeutic dose Pomponent 7 derivatives
) Fibrinogen HT units 75kg body wt [Eryoprecipitate(T00-250gms fibrinogentbag)
ji) Prothrombin 10-20m1 plasma Kg Plasma or prothrombin complex concentrate
ji) Factor V Omi fresh frozen plasma/kg fes frozen plasma
iv) Factor VIT 10-20m1 plasmalkg Plasma or prothrombin complex concentrate
) Factor Vit 175-50 units/kg rer (100 units/bag) factor VII concentrate
Factors IX 20-80 units/kg rothrombin complex concentrate plasma (1 unit of
factor IXAmI)
i) Factor X 10-20m1 plasmalkg Plasma or prothrombin complex
ii) Factor XI 10-20mi plasmalKg Plasma
) Factor XI 1-6 bags Cryoprecipitate or 500ml plasma pm or Cryoprecipitate
a
Dr Azam's Notes in Anesthesiology 2013
actor jerapeutic dose Pomponent 7 derivatives
) Fibrinogen HT units 75kg body wt [Eryoprecipitate(T00-250gms fibrinogentbag)
ji) Prothrombin 10-20m1 plasma Kg Plasma or prothrombin complex concentrate
ji) Factor V Omi fresh frozen plasma/kg fes frozen plasma
iv) Factor VIT 10-20m1 plasmalkg Plasma or prothrombin complex concentrate
) Factor Vit 175-50 units/kg rer (100 units/bag) factor VII concentrate
Factors IX 20-80 units/kg rothrombin complex concentrate plasma (1 unit of
factor IXAmI)
i) Factor X 10-20m1 plasmalkg Plasma or prothrombin complex
ii) Factor XI 10-20mi plasmalKg Plasma
) Factor XI 1-6 bags Cryoprecipitate or 500ml plasma pm or Cryoprecipitate
a
Dr Azam's Notes in Anesthesiology 2013
15. Partial thromboplastin time - PTT
Partial thromboplastin time:
+ PTT measures the intrinsic pathway i.e. factor
LV, VIH, XXI,
+ Specimen: citrate anticoagulated whole blood to be kept
refrigerated and transported as soon as possible.
+ Procedure: Performed with addition of contact activator (celite,
kaolin, micro silicate, ellagic acid).
+ Plasma sample is added to activator and incubated at 37°C for 5
minutes. Thromboplastin preparation is added, mixed with
addition CaClz and the timer is started.
Normal range: 25-39 seconds
+ Healthy premature babies have prolonged PT, PTT, TT which
retums to normal at 6 months.
+ Panic range:>70 seconds
Use:
+ Evaluation of intrinsic pathway, Heparin therapy, Screening for
hemophilia A and B (factor VIII) , dysfibrinogenemias, DIC, -
liver failure, Vitamin K deficiency
Contraindications:
+ Specimen obtained less than 3 hrs after heparin doses.
+ About 30% of normal concentration of factor V, Vill, IX, X, XI and
XII will maintain a rate of thrombin formation sufficient to
produce normal PTT. Prolongation occurs when any of the
above single clotting factor falls below this level
+ Heparin > active serine protease
Control of heparin therapy
+ Heparin is an acid mucopolysaccharides found in Mast cells and
Basophils, which inhibits all the active serine proteases like lla,
IXa, Xa, Xla and Xila.
+ Response to heparin can be measured by whole blood PTT,
APTT whole blood clotting time and PTT with comparable
responses.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Administration of heparin:
© on ©
oe Pp.
Heparin can be given subcutaneously / IV.
IV can be intermittent or continuous infusion.
Usually in dose of 400-500 units / kg / day divided into 6% hriy
dosage.
3 levels of heparin therapy.
Low dose (10,000 - 20,000 units/day) mainly used as prophylaxis
against venous thrombosis (DVT), measurable changes in APT
usually does not occurs.
Moderate dose (20,000 to 60,000 unitsklay) used in patient
without active thrombo embolic disease.
APTT is adjusted to 1% to 2 times the control.
High dose (60,000 to 1,00,000 units / day) used in patient with
active thrombo embolic disease,
This high dose is usually used for first 24-48 hrs and then
reversed back to a dose of 30,000-45,000 units/day.
42
Partial thromboplastin time:
+ PTT measures the intrinsic pathway i.e. factor
LV, VIH, XXI,
+ Specimen: citrate anticoagulated whole blood to be kept
refrigerated and transported as soon as possible.
+ Procedure: Performed with addition of contact activator (celite,
kaolin, micro silicate, ellagic acid).
+ Plasma sample is added to activator and incubated at 37°C for 5
minutes. Thromboplastin preparation is added, mixed with
addition CaClz and the timer is started.
Normal range: 25-39 seconds
+ Healthy premature babies have prolonged PT, PTT, TT which
retums to normal at 6 months.
+ Panic range:>70 seconds
Use:
+ Evaluation of intrinsic pathway, Heparin therapy, Screening for
hemophilia A and B (factor VIII) , dysfibrinogenemias, DIC, -
liver failure, Vitamin K deficiency
Contraindications:
+ Specimen obtained less than 3 hrs after heparin doses.
+ About 30% of normal concentration of factor V, Vill, IX, X, XI and
XII will maintain a rate of thrombin formation sufficient to
produce normal PTT. Prolongation occurs when any of the
above single clotting factor falls below this level
+ Heparin > active serine protease
Control of heparin therapy
+ Heparin is an acid mucopolysaccharides found in Mast cells and
Basophils, which inhibits all the active serine proteases like lla,
IXa, Xa, Xla and Xila.
+ Response to heparin can be measured by whole blood PTT,
APTT whole blood clotting time and PTT with comparable
responses.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Administration of heparin:
© on ©
oe Pp.
Heparin can be given subcutaneously / IV.
IV can be intermittent or continuous infusion.
Usually in dose of 400-500 units / kg / day divided into 6% hriy
dosage.
3 levels of heparin therapy.
Low dose (10,000 - 20,000 units/day) mainly used as prophylaxis
against venous thrombosis (DVT), measurable changes in APT
usually does not occurs.
Moderate dose (20,000 to 60,000 unitsklay) used in patient
without active thrombo embolic disease.
APTT is adjusted to 1% to 2 times the control.
High dose (60,000 to 1,00,000 units / day) used in patient with
active thrombo embolic disease,
This high dose is usually used for first 24-48 hrs and then
reversed back to a dose of 30,000-45,000 units/day.
42
16. Activated Clotting Time - ACT
Synonymous > Activated clotting time ground gloss clotting
time is a screening time for coagulation deficiencies and is
of special application to the monitoring of heparin effect.
Specimen: Fresh whole blood that is free of venepuncture
derived thromboplastin
Procedure: manually mixing of whole blood with an
activator substance such as celite / kaolin.
+ Contact of the activator with the blood initiates the
activation of the clotting cascade.
+ Commercially available timing systems are uses clinically
to measure the activated clotting time. These devices
detect the onset of clot formation.
+ Tubes of freshly drawn blood are incubated at 3700 and
tilted at 300 second intervals until the flow of blood stops.
+ Tilting and recording can be made manually or by
automated machines.
Normal range > 9-120 seconds (Miller's text 107 13
seconds)
Limitations > Relatively insensitive to lower
concentration of heparin
+ Insensitive to factor VII deficiency
+ Hypothermia and haemodilution > prolongs ACT
+ It assays over all coagulation activity and during
monitoring for heparin therapy, prolonged values may not
be exclusively due to heparin therapy.
+ Abnormal values due to platelet abnormality.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Uses:
+ Monitoring of heparin therapy.
+ Abaseline value of ACT is determined
- Before IV administration of heparin
- Approximately 3 mins after administration
- 30 mins intervals thereatter.
+ Use to monitor anticoagulation when large doses of heparin are
used as during cordial surgical procedure.
+ During CPB the anticoagulant effect of heparin is often is
considered as adequate if the ACT is more than 300 seconds,
questionable with ACT between 300-180 sec and inadequate with
ACT < 180 sec.
- In patients receiving antifibrinolytic agent aprotinin, kaolin should be
used to measure ACT, because it will bind the aprotinin and remove
it from the plasma.
During CPB:
+ ACT = 300 - Adequate
+ ACT = 300 - 1800 Questionable
+ ACT =< 180 in adequate
Synonymous > Activated clotting time ground gloss clotting
time is a screening time for coagulation deficiencies and is
of special application to the monitoring of heparin effect.
Specimen: Fresh whole blood that is free of venepuncture
derived thromboplastin
Procedure: manually mixing of whole blood with an
activator substance such as celite / kaolin.
+ Contact of the activator with the blood initiates the
activation of the clotting cascade.
+ Commercially available timing systems are uses clinically
to measure the activated clotting time. These devices
detect the onset of clot formation.
+ Tubes of freshly drawn blood are incubated at 3700 and
tilted at 300 second intervals until the flow of blood stops.
+ Tilting and recording can be made manually or by
automated machines.
Normal range > 9-120 seconds (Miller's text 107 13
seconds)
Limitations > Relatively insensitive to lower
concentration of heparin
+ Insensitive to factor VII deficiency
+ Hypothermia and haemodilution > prolongs ACT
+ It assays over all coagulation activity and during
monitoring for heparin therapy, prolonged values may not
be exclusively due to heparin therapy.
+ Abnormal values due to platelet abnormality.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Uses:
+ Monitoring of heparin therapy.
+ Abaseline value of ACT is determined
- Before IV administration of heparin
- Approximately 3 mins after administration
- 30 mins intervals thereatter.
+ Use to monitor anticoagulation when large doses of heparin are
used as during cordial surgical procedure.
+ During CPB the anticoagulant effect of heparin is often is
considered as adequate if the ACT is more than 300 seconds,
questionable with ACT between 300-180 sec and inadequate with
ACT < 180 sec.
- In patients receiving antifibrinolytic agent aprotinin, kaolin should be
used to measure ACT, because it will bind the aprotinin and remove
it from the plasma.
During CPB:
+ ACT = 300 - Adequate
+ ACT = 300 - 1800 Questionable
+ ACT =< 180 in adequate
17. Prothrombin Time - PT
+ PT, measures the extrinsic pathway (I, II, V, VI, X) of
coagulation and common pathway.
‘Specimen > sodium Citrated anticoagulated whole blood.
Procedure > clotting time of Citrated anticoagulated plasma
is determined after the addition of optimum concentration of
calcium and an excess of thromboplastin. Clot detection is
either normal or by an automated device
+ The final result depends on the concentration and source of
thromboplastin, calcium concentration and the method used
to detect clot formation. Therefore results may vary a great
deal from laboratory to laboratory.
+ Normal range — 10-14 seconds.
+ Premature, new bom have normally prolonged PT, TT,
APTT which comes to normal range by 6 months.
+ Panic range >> 20 secs > non anticoagulated
- 3 times control > anticoagulated
Use:
+ Useful in screening for deficiency of prothrombin,
dysfibrinogenemias, afibrinogenemia, liver failure, DIC,
heparin effects, coumarin / warfarin effects, screening of
vitamin K deficiency, and factor V, VII, & X (5, 7, 10)
- Prolongation of the PT usually reflects severe liver
decrease unless vitamin K deficiency is present because
only 20-30% of normal factor activity is required
+ Failure of the PT to correct, following parenteral
administration of vitamin K implies severe liver disease,
correction normally requires 24 hrs.
+ Limitations — PT drawn less than 2 hrs after heparin
administration Is prolonged( minimum duration is more than
6 hrs).
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
INR (INTERNATIONAL NORMALIZED RATIO)
- The INR was established as a mean of standardizing the PT for oral
anticoagulant therapy.
Calculated as INR= PT of patient (sec)
Mean of normal PT(ISI)
+ INR rate is used in monitoring patient in oral anticoagulant therapy
and itis recommended to monitor. INR of 1.3-1.5 (15-18 seconds) but
slightly higher range of 1.5-2.0 is recommended for patients with
prosthetic valves and recurrent embolism
+ INR of 1.5 to 2.0 in prosthetic valve and recurrent embolism.
+ PT, measures the extrinsic pathway (I, II, V, VI, X) of
coagulation and common pathway.
‘Specimen > sodium Citrated anticoagulated whole blood.
Procedure > clotting time of Citrated anticoagulated plasma
is determined after the addition of optimum concentration of
calcium and an excess of thromboplastin. Clot detection is
either normal or by an automated device
+ The final result depends on the concentration and source of
thromboplastin, calcium concentration and the method used
to detect clot formation. Therefore results may vary a great
deal from laboratory to laboratory.
+ Normal range — 10-14 seconds.
+ Premature, new bom have normally prolonged PT, TT,
APTT which comes to normal range by 6 months.
+ Panic range >> 20 secs > non anticoagulated
- 3 times control > anticoagulated
Use:
+ Useful in screening for deficiency of prothrombin,
dysfibrinogenemias, afibrinogenemia, liver failure, DIC,
heparin effects, coumarin / warfarin effects, screening of
vitamin K deficiency, and factor V, VII, & X (5, 7, 10)
- Prolongation of the PT usually reflects severe liver
decrease unless vitamin K deficiency is present because
only 20-30% of normal factor activity is required
+ Failure of the PT to correct, following parenteral
administration of vitamin K implies severe liver disease,
correction normally requires 24 hrs.
+ Limitations — PT drawn less than 2 hrs after heparin
administration Is prolonged( minimum duration is more than
6 hrs).
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
INR (INTERNATIONAL NORMALIZED RATIO)
- The INR was established as a mean of standardizing the PT for oral
anticoagulant therapy.
Calculated as INR= PT of patient (sec)
Mean of normal PT(ISI)
+ INR rate is used in monitoring patient in oral anticoagulant therapy
and itis recommended to monitor. INR of 1.3-1.5 (15-18 seconds) but
slightly higher range of 1.5-2.0 is recommended for patients with
prosthetic valves and recurrent embolism
+ INR of 1.5 to 2.0 in prosthetic valve and recurrent embolism.
operative coagulopathy?
[18. Describe the coagulation factors. How do you Investigate a case of intra
+ Coagulation, often referred to as secondary hemostasis:
involves formation of a fibrin clot, which usually binds and
strengthens a platelet plug,
+ Fibrin can be formed via one of the 2 pathways that involve
activation of soluble coagulation precursor proteins in blood
Coagulation factors:
I Fibrinogen
I Prothrombin
Il Tissue thromboplastin
IV Calcium/Labile Factor
V Proaocelerin
Vil Proconvertin
VIII Antihemophilic factor
IX Christmas factor
X Straut power factor
XI Plasma thromboplastin antecedents (PTA
XI! Hageman factor
XIII Fibrin stabilizing factor (Laki-Lorand factor)
Factors contributing to excessive bleeding during and following
surgery:
+ Hemostasis following trauma and surgery is dependent on 3
major processes. A defect in any of the following leads to
bleeding diathesis and increased blood loss.
Seconds:
1. Vascular spasm
2. Formation of platelet plug - primary hemostasis
Minutes:
+ Coagulation of blood — secondary hemostasis
+ Vascular spasm: result of release of humoral factors and local
myogenic reflexes.
+ Sympathetic mediated vasoconstriction in medium - sized
vessels.
Dr Azam's Notes in Anesthesiology 2013
Primary hemostasis: Platelet plug formation
3 stages
1. Adhesion circulating platelets adhere to subendothelial collagen via
specific glycoprotein receptor. Stabilized by circulating glycoprotein
called vWf which forms additional bridges via GPlb.
2. Release of platelet granules: collagen (as well as epinephrine and
thrombin) activates platelet membrane bound
Phospholipase A c
J ¿
Formation of TXA, Degranulation
¿
ADP, THA, Falor V VW, Fibrinogen
ni il
Potent vasoconstrictor onl Aivonertis
3. Aggregation: These factors attract and activate additional
platelets — resulting in platelet plug.
4, Coagulation cascade: Fibrin can be formed via one of the 2
pathways.
+ The extrinsic pathway — triggered by the release of tissue
lipoprotein (thromboplastin) from injured cells.
+ More important pathway in humans.
+ Factors involved — 1, 2, 5, 7 and 10.
+ Test prothrombin time.
45
Dr Azam's Notes in Anesthesiology 2013
[18. Describe the coagulation factors. How do you Investigate a case of intra
+ Coagulation, often referred to as secondary hemostasis:
involves formation of a fibrin clot, which usually binds and
strengthens a platelet plug,
+ Fibrin can be formed via one of the 2 pathways that involve
activation of soluble coagulation precursor proteins in blood
Coagulation factors:
I Fibrinogen
I Prothrombin
Il Tissue thromboplastin
IV Calcium/Labile Factor
V Proaocelerin
Vil Proconvertin
VIII Antihemophilic factor
IX Christmas factor
X Straut power factor
XI Plasma thromboplastin antecedents (PTA
XI! Hageman factor
XIII Fibrin stabilizing factor (Laki-Lorand factor)
Factors contributing to excessive bleeding during and following
surgery:
+ Hemostasis following trauma and surgery is dependent on 3
major processes. A defect in any of the following leads to
bleeding diathesis and increased blood loss.
Seconds:
1. Vascular spasm
2. Formation of platelet plug - primary hemostasis
Minutes:
+ Coagulation of blood — secondary hemostasis
+ Vascular spasm: result of release of humoral factors and local
myogenic reflexes.
+ Sympathetic mediated vasoconstriction in medium - sized
vessels.
Dr Azam's Notes in Anesthesiology 2013
Primary hemostasis: Platelet plug formation
3 stages
1. Adhesion circulating platelets adhere to subendothelial collagen via
specific glycoprotein receptor. Stabilized by circulating glycoprotein
called vWf which forms additional bridges via GPlb.
2. Release of platelet granules: collagen (as well as epinephrine and
thrombin) activates platelet membrane bound
Phospholipase A c
J ¿
Formation of TXA, Degranulation
¿
ADP, THA, Falor V VW, Fibrinogen
ni il
Potent vasoconstrictor onl Aivonertis
3. Aggregation: These factors attract and activate additional
platelets — resulting in platelet plug.
4, Coagulation cascade: Fibrin can be formed via one of the 2
pathways.
+ The extrinsic pathway — triggered by the release of tissue
lipoprotein (thromboplastin) from injured cells.
+ More important pathway in humans.
+ Factors involved — 1, 2, 5, 7 and 10.
+ Test prothrombin time.
45
Dr Azam's Notes in Anesthesiology 2013
[Describe the coagulation factors. How do you investigate a case of intra operative
[coagulopathy2Continuation:
Intrinsic pathway:
+ Triggered by interaction between sub-endothelial collagen with circulating factor XII,
HMWK and prekallikrein.
+ Factors involved - 1, 2, 5, 8, 9, 10, 11,12,
+ Test PTT
+ Regardless of pathway activated, the coagulation cascade is ends in the conversion
of fibrinogen to fibrin.
+ Thrombin plays a central role in coagulation.
+ Thrombin then converts fibrinogen to soluble fibrin monomers that polymerize on
the platelet plug.
Tests for coagulation:
Test Normal value Measured
H) Bleeding time 10 minutes Platelet function vascular integrity
2) Platelet count (150,000 to 400,000 cells?
pas
8) Prothrombin time 10-12 seconds Factors 1, 2,5, 7, 10
PTT 25-35 secs Factors 1, 2, 5, 7, 9,10, 11,12
p Activated clotting time 180-120 secs Fame as above
6) Thrombin time 10-17 seconds Factors 1,2
17) Fibrinogen 150-250 mg/d
) Fibrin degradation Amgmi
roduct
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
[coagulopathy2Continuation:
Intrinsic pathway:
+ Triggered by interaction between sub-endothelial collagen with circulating factor XII,
HMWK and prekallikrein.
+ Factors involved - 1, 2, 5, 8, 9, 10, 11,12,
+ Test PTT
+ Regardless of pathway activated, the coagulation cascade is ends in the conversion
of fibrinogen to fibrin.
+ Thrombin plays a central role in coagulation.
+ Thrombin then converts fibrinogen to soluble fibrin monomers that polymerize on
the platelet plug.
Tests for coagulation:
Test Normal value Measured
H) Bleeding time 10 minutes Platelet function vascular integrity
2) Platelet count (150,000 to 400,000 cells?
pas
8) Prothrombin time 10-12 seconds Factors 1, 2,5, 7, 10
PTT 25-35 secs Factors 1, 2, 5, 7, 9,10, 11,12
p Activated clotting time 180-120 secs Fame as above
6) Thrombin time 10-17 seconds Factors 1,2
17) Fibrinogen 150-250 mg/d
) Fibrin degradation Amgmi
roduct
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
19, Categorization of coagulation disorders:
Hereditary
Hemophilia A and B
Von Willebrand disease
Afibronoginemia
Factor V def
Factor Vill def
Proteine def
Antithrombin lll def
+ FFP — 1 u/ml of factor VIII
+ Cryoprecipitate— 5 -10 u/ml factor VIII
Acquired
DIC
Perioperative anticoagulation
Intra operative coagulation
—+- Dilutional thrombocyte
penta
|_,- Dilution of procoagulants
L- Massive blood transfusion
L%- Type of surgery
(CPB, Brain trauma,
orthopedic, obstetric)
Drug induced hemorrhage
Drug induced platelet dysfunction
ITP
TIP
Catheter-induced thrombosis
vitamin K def.
+ Factor VIII concentration — 40 u/ml factor VIII
+ DDAV - 1 2to 3 times.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
47
Hereditary
Hemophilia A and B
Von Willebrand disease
Afibronoginemia
Factor V def
Factor Vill def
Proteine def
Antithrombin lll def
+ FFP — 1 u/ml of factor VIII
+ Cryoprecipitate— 5 -10 u/ml factor VIII
Acquired
DIC
Perioperative anticoagulation
Intra operative coagulation
—+- Dilutional thrombocyte
penta
|_,- Dilution of procoagulants
L- Massive blood transfusion
L%- Type of surgery
(CPB, Brain trauma,
orthopedic, obstetric)
Drug induced hemorrhage
Drug induced platelet dysfunction
ITP
TIP
Catheter-induced thrombosis
vitamin K def.
+ Factor VIII concentration — 40 u/ml factor VIII
+ DDAV - 1 2to 3 times.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
47
20. Describe various test used for monitoring peri-operative coagulation.
Traditionally, perioperative coagulation monitoring has focused on:
(1) preoperative testing to identify patients at increased risk for perioperative bleeding
(2) intraoperative monitoring of heparin therapy during cardiac and vascular surgery.
[Test tor Monitoring Perioperative Coagulation.
eet
Partial thromboplastin time:
+ PTT measures the intrinsic pathway Le. factor
1,1, VIV, 1X, XXI, XI
+ Normal range: 25-39 seconds
+ Healthy premature babies have prolonged PT,
PTT, TT which retums to normal at 6 months.
+ Panic range:> 70 seconds
+ Use:
+ Evaluation of intrinsic pathway, Heparin therapy,
Screening for hemophilia A and B (factor VIII),
dysfibrinogenemias, DIC, -liver failure, Vitamin K
deficiency
+ Control of heparin therapy
+ Heparin is an acid mucopolysaccharides found in
Mast cells and Basophils, which inhibits all the
active serine proteases like lla, IXa, Xa, Xia and
XIe.
+ Response to heparin can be measured by whole
blood PTT, APTT whole blood clotting time and
PTT with comparable responses.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam’s Notes in Anesthesiology 2013
y Ts,
PROTHROMBIN TIME:
|. PT, measures the extrinsic pathway (|, Il, V, VII, X) of
coagulation and common pathway.
|: Normal range — 10-14 seconds.
|. Premature, new bom have normally prolonged PT, TT,
APTT which comes to normal range by 6 months.
|. Panic range >> 20 sec > non anticoagulated
| 3 times control > anticoagulated
lUse:
|- Useful in screening for deficiency of prothrombin,
dysfibrinogenemias, afibrinogenemia, liver failure, DIC,
heparin effects, coumarin / warfarin effects, screening
of vitamin K deficiency, and factor Ve VII, & X (5, 7,
10)
|- Prolongation of the PT usually reflects severe liver
decrease unless vitamin K deficiency is present
because only 20-30% of normal factor activity is
required.
|. Failure of the PT to correct, following parenteral
administration of vitamin K implies severe liver
disease, correction normally requires 24 hrs.
|. Limitations — PT drawn less than 2 hrs after heparin
administration is prolonged( minimum duration is more
than 6 hrs)
INR (INTERNATIONAL NORMALIZED
RATIO):
+ The INR was established as a
mean of standardizing the PT for
oral anticoagulant therapy.
+ Calculated as INR = PT of patient
(sec)/ Mean of normal range
INR rate is used in monitoring
patient in oral anticoagulant
therapy and it is recommended to
monitor. INR of 1.3-1.5 (15-18
seconds) but slightly higher range
of 1.5-2.0 is recommended for
patients with prosthetic valves and
recurrent embolism,
INR of 1.5 to 2.0 in prosthetic valve
and recurrent embolism.
Traditionally, perioperative coagulation monitoring has focused on:
(1) preoperative testing to identify patients at increased risk for perioperative bleeding
(2) intraoperative monitoring of heparin therapy during cardiac and vascular surgery.
[Test tor Monitoring Perioperative Coagulation.
eet
Partial thromboplastin time:
+ PTT measures the intrinsic pathway Le. factor
1,1, VIV, 1X, XXI, XI
+ Normal range: 25-39 seconds
+ Healthy premature babies have prolonged PT,
PTT, TT which retums to normal at 6 months.
+ Panic range:> 70 seconds
+ Use:
+ Evaluation of intrinsic pathway, Heparin therapy,
Screening for hemophilia A and B (factor VIII),
dysfibrinogenemias, DIC, -liver failure, Vitamin K
deficiency
+ Control of heparin therapy
+ Heparin is an acid mucopolysaccharides found in
Mast cells and Basophils, which inhibits all the
active serine proteases like lla, IXa, Xa, Xia and
XIe.
+ Response to heparin can be measured by whole
blood PTT, APTT whole blood clotting time and
PTT with comparable responses.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam’s Notes in Anesthesiology 2013
y Ts,
PROTHROMBIN TIME:
|. PT, measures the extrinsic pathway (|, Il, V, VII, X) of
coagulation and common pathway.
|: Normal range — 10-14 seconds.
|. Premature, new bom have normally prolonged PT, TT,
APTT which comes to normal range by 6 months.
|. Panic range >> 20 sec > non anticoagulated
| 3 times control > anticoagulated
lUse:
|- Useful in screening for deficiency of prothrombin,
dysfibrinogenemias, afibrinogenemia, liver failure, DIC,
heparin effects, coumarin / warfarin effects, screening
of vitamin K deficiency, and factor Ve VII, & X (5, 7,
10)
|- Prolongation of the PT usually reflects severe liver
decrease unless vitamin K deficiency is present
because only 20-30% of normal factor activity is
required.
|. Failure of the PT to correct, following parenteral
administration of vitamin K implies severe liver
disease, correction normally requires 24 hrs.
|. Limitations — PT drawn less than 2 hrs after heparin
administration is prolonged( minimum duration is more
than 6 hrs)
INR (INTERNATIONAL NORMALIZED
RATIO):
+ The INR was established as a
mean of standardizing the PT for
oral anticoagulant therapy.
+ Calculated as INR = PT of patient
(sec)/ Mean of normal range
INR rate is used in monitoring
patient in oral anticoagulant
therapy and it is recommended to
monitor. INR of 1.3-1.5 (15-18
seconds) but slightly higher range
of 1.5-2.0 is recommended for
patients with prosthetic valves and
recurrent embolism,
INR of 1.5 to 2.0 in prosthetic valve
and recurrent embolism.
[Describe various test used for monitoring peri-operative coagulation.Continuation:
[Test for Monitoring Perioperative Coagulation.
—
ACTIVATED COAGULATION TIME (ACT):
+ Activated clotting time ground gloss clotting time is a
screening time for coagulation deficiencies and is of
special application to the monitoring of heparin effect
+ Normal range > 9-120 seconds (Miller's text 1072
13 seconds)
Uses:
+ Monitoring of heparin therapy.
+ Abaseline value of ACT is determined
i. Before IV administration of heparin
ii, Approximately 3 mins after administration
iii, 80 mins intervals thereafter.
+ Use to monitor anticoagulation when large doses of
heparin are used as during cordial surgical procedure.
+ During CPB the anticoagulant effect of heparin is
often is considered as adequate if the ACT is more
than 300 seconds, questionable with ACT between
300-180 sec and inadequate with ACT < 180 sec.
In patients receiving antifibrinolytics agent aprotinin,
kaolin should be used to measure ACT, because it will
bind the aprotinin and remove it from the plasma
Dr Azam's Notes in Anesthesiology 2013
y
THROMBOELASTOGRAPHY:
+ Itis a viscous elastic technique which
measures entire spectrum of clot formation
from early fibrin strands to clot retraction and
eventual fibrinolysis. This test evaluate clot
formation as a dynamic process unlike
standard coagulation tests which measure
isolated endpoints.
a ar +
R— Reaction time for initial fibrin formation
N > 6-8 mins
1 in deficiency of a coagulation factors,
R + K > coagulation time
N > 10-12 mins.
0° clot formation rate
N >> 50%) in coagulation disorder.
MA > Maximum Amplitude
Aso Amplitude 60 min other MA
F > Whole blood clot lysis time
N >> 300 min
Dr Azam’s Notes in Anesthesiology 2013
Uses:
+ Coagulation monitoring during
+ Liver transplantation
+ Obstetric anesthesia
+ Trauma anesthesia (massive
transfusion)
+ Diagnosis pre-coagulant defect.
- Platelet dysfunction
- Fibrinolysis
- Hyper-coagulation state
+ Real time detection of clotting
abnormalities in liver
transplantation CPB
+ Differentiates surgical bleeding
from coagulopathy in cardiac
surgery.
49
[Test for Monitoring Perioperative Coagulation.
—
ACTIVATED COAGULATION TIME (ACT):
+ Activated clotting time ground gloss clotting time is a
screening time for coagulation deficiencies and is of
special application to the monitoring of heparin effect
+ Normal range > 9-120 seconds (Miller's text 1072
13 seconds)
Uses:
+ Monitoring of heparin therapy.
+ Abaseline value of ACT is determined
i. Before IV administration of heparin
ii, Approximately 3 mins after administration
iii, 80 mins intervals thereafter.
+ Use to monitor anticoagulation when large doses of
heparin are used as during cordial surgical procedure.
+ During CPB the anticoagulant effect of heparin is
often is considered as adequate if the ACT is more
than 300 seconds, questionable with ACT between
300-180 sec and inadequate with ACT < 180 sec.
In patients receiving antifibrinolytics agent aprotinin,
kaolin should be used to measure ACT, because it will
bind the aprotinin and remove it from the plasma
Dr Azam's Notes in Anesthesiology 2013
y
THROMBOELASTOGRAPHY:
+ Itis a viscous elastic technique which
measures entire spectrum of clot formation
from early fibrin strands to clot retraction and
eventual fibrinolysis. This test evaluate clot
formation as a dynamic process unlike
standard coagulation tests which measure
isolated endpoints.
a ar +
R— Reaction time for initial fibrin formation
N > 6-8 mins
1 in deficiency of a coagulation factors,
R + K > coagulation time
N > 10-12 mins.
0° clot formation rate
N >> 50%) in coagulation disorder.
MA > Maximum Amplitude
Aso Amplitude 60 min other MA
F > Whole blood clot lysis time
N >> 300 min
Dr Azam’s Notes in Anesthesiology 2013
Uses:
+ Coagulation monitoring during
+ Liver transplantation
+ Obstetric anesthesia
+ Trauma anesthesia (massive
transfusion)
+ Diagnosis pre-coagulant defect.
- Platelet dysfunction
- Fibrinolysis
- Hyper-coagulation state
+ Real time detection of clotting
abnormalities in liver
transplantation CPB
+ Differentiates surgical bleeding
from coagulopathy in cardiac
surgery.
49
Dr Azam’s Notes in Anesthesiology 2013
[Describe various test used for monitoring peri-operative coagulation. Continuation:
[THROMBOELASTOGRAPHY: Continuation: Characteristic Thromboelastograph Tracings
sora =
Thrombocytopenia aml
Severe Platelet Dysfunction mens
. 4 4 4 Coagulation Factor Deficiency —-« iil
formal | _ Hemophilic | Thrombocytopenia [Fibrinolysis —[ypercoagulability Frings >
D) ProlongedR | 1) Prolonged R JD | MA ) Shortened R
Di Die ie BT Ma Hypercoagulable State Ga
DIMA LMA Dir lp Prolonged F e
Treatment for the TEG:
TEG Parameters Treatment
AM - 14 min 2x FFP or 10 mikg
R> 14min 4x FFP or 20 mikg
MA 46- 50 mm 1 Platelet concentrates
MA < 46 mm 2 platelet concentrates
‘Angle < 52° 2x FFP or cryoprecipitate
Ly 30 > 8% Antifibrinolyiics
Dr Azam's Notes in Anesthesiology 2013
[Describe various test used for monitoring peri-operative coagulation. Continuation:
[THROMBOELASTOGRAPHY: Continuation: Characteristic Thromboelastograph Tracings
sora =
Thrombocytopenia aml
Severe Platelet Dysfunction mens
. 4 4 4 Coagulation Factor Deficiency —-« iil
formal | _ Hemophilic | Thrombocytopenia [Fibrinolysis —[ypercoagulability Frings >
D) ProlongedR | 1) Prolonged R JD | MA ) Shortened R
Di Die ie BT Ma Hypercoagulable State Ga
DIMA LMA Dir lp Prolonged F e
Treatment for the TEG:
TEG Parameters Treatment
AM - 14 min 2x FFP or 10 mikg
R> 14min 4x FFP or 20 mikg
MA 46- 50 mm 1 Platelet concentrates
MA < 46 mm 2 platelet concentrates
‘Angle < 52° 2x FFP or cryoprecipitate
Ly 30 > 8% Antifibrinolyiics
Dr Azam's Notes in Anesthesiology 2013
21, Thromboelastography
Definition:
+ Itis a viscous elastic technique which measures entire spectrum of
clot formation from early fibrin strands to clot retraction and eventual
fibrinolysis. This test evaluate clot formation as a dynamic process
unlike standard coagulation tests which measure isolated endpoints.
Method of recording:
+ 0.35 ml of blood placed in a disposable curette within the instrument
The curette continuously rotates around an axis of 50.
+ A metal piston attached by a tissue wire to an electronic needle
recorder is lowered into the blood in the curette. A clot formation
occurs, the piston become with in the clot & the solution of curette is
then transfused to piston and to the electronic recorder.
+ Hyper coagulated within 30 min of obtaining the sample.
+ Itaids in the diagnosis of a procoagulation deficiency (hemophilia),
platelet dysfunction, fibrinolysis, DIC.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Reaction time for initial fibrin formation
N > 6-8 mins
1 in deficiency of a coagulation factors.
R + K > coagulation time
N > 10-12 mins
a clot formation rate
N >> 500) in coagulation disorder.
MA > Maximum Amplitude
Aso> Amplitude 60 min other MA
F > Whole blood clot lysis time
N >> 300 min
Uses:
+ Coagulation monitoring during
+ Liver transplantation
+ Obstetric anesthesia
+ Trauma anesthesia (massive transfusion)
Uses:
Diagnosis pre-coagulant defect.
- Platelet dysfunction
- Fibrinolysis
- Hyper-coagulation state
Real time detection of clotting abnormalities in liver
transplantation CPB
Difterentiates surgical bleeding from coagulopathy in cardiac
surgery.
Disadvantages:
Lack of specificity associated with abnormal findings
Qualitative assessment is not possible
Schematic depiction of coagulopathy as selected by the
Thromboelastography compared with normal one
si
Definition:
+ Itis a viscous elastic technique which measures entire spectrum of
clot formation from early fibrin strands to clot retraction and eventual
fibrinolysis. This test evaluate clot formation as a dynamic process
unlike standard coagulation tests which measure isolated endpoints.
Method of recording:
+ 0.35 ml of blood placed in a disposable curette within the instrument
The curette continuously rotates around an axis of 50.
+ A metal piston attached by a tissue wire to an electronic needle
recorder is lowered into the blood in the curette. A clot formation
occurs, the piston become with in the clot & the solution of curette is
then transfused to piston and to the electronic recorder.
+ Hyper coagulated within 30 min of obtaining the sample.
+ Itaids in the diagnosis of a procoagulation deficiency (hemophilia),
platelet dysfunction, fibrinolysis, DIC.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Reaction time for initial fibrin formation
N > 6-8 mins
1 in deficiency of a coagulation factors.
R + K > coagulation time
N > 10-12 mins
a clot formation rate
N >> 500) in coagulation disorder.
MA > Maximum Amplitude
Aso> Amplitude 60 min other MA
F > Whole blood clot lysis time
N >> 300 min
Uses:
+ Coagulation monitoring during
+ Liver transplantation
+ Obstetric anesthesia
+ Trauma anesthesia (massive transfusion)
Uses:
Diagnosis pre-coagulant defect.
- Platelet dysfunction
- Fibrinolysis
- Hyper-coagulation state
Real time detection of clotting abnormalities in liver
transplantation CPB
Difterentiates surgical bleeding from coagulopathy in cardiac
surgery.
Disadvantages:
Lack of specificity associated with abnormal findings
Qualitative assessment is not possible
Schematic depiction of coagulopathy as selected by the
Thromboelastography compared with normal one
si
Dr Azamı's Notes in Anesthesiology 2013
Characteristic Thromboelastograph Tracings
FFhromboelastography
Normal
Thrombocytopenia
Severe Platelet Dysfunction
| "1 | \ \ Coagulation Factor Deficiency
lormal Hemophilic [Thrombocytopenia [Fibrinolysis |Hypercoagulability
1) Prolonged R |1) Prolonged R ly | ma It) Shortened R Fibrinolysis
) oP By la? ) by TMA a
DT MA 03 DIF la Profonged F
Hypercoagulable State
FR - Reaction time fibrin formation
| K- Time & Kinetics for fibrin cross linkage. EE TER
| a (Alpha) - Strength of the clot & clot formation reament forthe 1ES:
ratio. TEG Parameters Treatment
|. MA - Maximum Amplitude for fibrin & platelet
arten e P R11-14min 2x FFP or 10 mi/Kg
|. Ly 30 - Measures lysis time after MA. TO PEI
MA 46 - 50 mm 1 Platelet concentrates
MA< 46 mm 2 platelet concentrates
Angle < 52° 2x FFP or cryoprecipitate
Ly 30> 8% Antiibrinolytics
Dr Azam's Notes in Anesthesiology 2013
Brule
52
Characteristic Thromboelastograph Tracings
FFhromboelastography
Normal
Thrombocytopenia
Severe Platelet Dysfunction
| "1 | \ \ Coagulation Factor Deficiency
lormal Hemophilic [Thrombocytopenia [Fibrinolysis |Hypercoagulability
1) Prolonged R |1) Prolonged R ly | ma It) Shortened R Fibrinolysis
) oP By la? ) by TMA a
DT MA 03 DIF la Profonged F
Hypercoagulable State
FR - Reaction time fibrin formation
| K- Time & Kinetics for fibrin cross linkage. EE TER
| a (Alpha) - Strength of the clot & clot formation reament forthe 1ES:
ratio. TEG Parameters Treatment
|. MA - Maximum Amplitude for fibrin & platelet
arten e P R11-14min 2x FFP or 10 mi/Kg
|. Ly 30 - Measures lysis time after MA. TO PEI
MA 46 - 50 mm 1 Platelet concentrates
MA< 46 mm 2 platelet concentrates
Angle < 52° 2x FFP or cryoprecipitate
Ly 30> 8% Antiibrinolytics
Dr Azam's Notes in Anesthesiology 2013
Brule
52
22, Assessment of blood Loss during Surgery
+ Normal blood volume in an adult is 70mi/kg
for 17.7% of body weight. Total blood
volume can be measured as the sum of the
red cell volume and plasma volume or from
formulae depending on height and weight.
+ One of the most important tasks of
anesthesiologist is to continuously monitor
and estimates blood loss. Unless estimates
are complicated by occult bleeding into
wound or under surgical drapes, accuracy
is importance to guide fluid therapy
transfusion.
+ Most commonly used method for
estimating blood loss is measurement of
blood in surgical container and visually
estimating blood on surgical sponges and
laparotomy pads.
+ Afully soaked sponge (4x4) said to hold 10
ml of blood; where as soaked lap holds
100-150 ml
+ More accurate estimates are obtained if
sponges and laps are weighed before &
after use.
+ Serial hematocrit / hemoglobin
concentration reflect ratio of blood loss to
plasma, not necessarily blood loss.
Hematocrits may be useful during long
procedure or when estimates are difficult
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Measurement of blood loss:
1) Visual observation of degree of bleeding
2) Clinical signs: give indirect information conceming blood loss. These include fall
in BP, fall in C.VP,, tachycardia, sweating and pallor of skin. It is advantageous to
replace blood loss before these signs become evident
These methods give a reasonable estimate in the case of minimal blood loss.
Errors are likely to be cumulative if blood loss continues over a prolonged period.
3) Gravimetric method — simplest, most common employed blood loss estimate by
measurements of gain in weight of swabs and towels, together with measurement
of contents of suction bottle. 1m of blood weighs 1g.
Weighing of swabs underestimates blood loss by 25%.
4) Dilutional methods:
a) colorimetric method
b) use of radioactive tracer
a. Calorimetric method — swab + towel mixed thoroughly with large known volume
of fluid which is then estimate calorimetrically. Error may occur due to
incomplete extraction or contamination with bile. patient hemoglobin must be
known.
Blood loss = Calorimeter reading X Volume of Solution/200 X% of Pt Hb
In operations involving complex exchanges of blood (extracorporeal circulation). It
may be useful to weigh whole patient before and after operation
b) Use of radioactive tracer dilution methods:
When measuring the volume of anybody compartment by this method, itis
important that the tracer used remain within that compartment.
In the case of blood volume, either the patient's own red blood cells (labelled with
Cr following incubation with the isotope or pooled human albumin (labelled with
1'3 or 1131) are used. All 3 isotopes are gamma emitters, but 2s the isotope of
choice because it emits less energy. The activity of the tracer is first measured and
then injected intravenously.
+ Normal blood volume in an adult is 70mi/kg
for 17.7% of body weight. Total blood
volume can be measured as the sum of the
red cell volume and plasma volume or from
formulae depending on height and weight.
+ One of the most important tasks of
anesthesiologist is to continuously monitor
and estimates blood loss. Unless estimates
are complicated by occult bleeding into
wound or under surgical drapes, accuracy
is importance to guide fluid therapy
transfusion.
+ Most commonly used method for
estimating blood loss is measurement of
blood in surgical container and visually
estimating blood on surgical sponges and
laparotomy pads.
+ Afully soaked sponge (4x4) said to hold 10
ml of blood; where as soaked lap holds
100-150 ml
+ More accurate estimates are obtained if
sponges and laps are weighed before &
after use.
+ Serial hematocrit / hemoglobin
concentration reflect ratio of blood loss to
plasma, not necessarily blood loss.
Hematocrits may be useful during long
procedure or when estimates are difficult
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Measurement of blood loss:
1) Visual observation of degree of bleeding
2) Clinical signs: give indirect information conceming blood loss. These include fall
in BP, fall in C.VP,, tachycardia, sweating and pallor of skin. It is advantageous to
replace blood loss before these signs become evident
These methods give a reasonable estimate in the case of minimal blood loss.
Errors are likely to be cumulative if blood loss continues over a prolonged period.
3) Gravimetric method — simplest, most common employed blood loss estimate by
measurements of gain in weight of swabs and towels, together with measurement
of contents of suction bottle. 1m of blood weighs 1g.
Weighing of swabs underestimates blood loss by 25%.
4) Dilutional methods:
a) colorimetric method
b) use of radioactive tracer
a. Calorimetric method — swab + towel mixed thoroughly with large known volume
of fluid which is then estimate calorimetrically. Error may occur due to
incomplete extraction or contamination with bile. patient hemoglobin must be
known.
Blood loss = Calorimeter reading X Volume of Solution/200 X% of Pt Hb
In operations involving complex exchanges of blood (extracorporeal circulation). It
may be useful to weigh whole patient before and after operation
b) Use of radioactive tracer dilution methods:
When measuring the volume of anybody compartment by this method, itis
important that the tracer used remain within that compartment.
In the case of blood volume, either the patient's own red blood cells (labelled with
Cr following incubation with the isotope or pooled human albumin (labelled with
1'3 or 1131) are used. All 3 isotopes are gamma emitters, but 2s the isotope of
choice because it emits less energy. The activity of the tracer is first measured and
then injected intravenously.
‘Assessment of blood Loss during Surgery Dr Azam's Notes in Anesthesiology 2013
+ The activity remaining in the empty syringe is measured and Exact point Is based on patient's medical condition & surgical
deducted from the amount of the isotope injected. After 10-15 procedure.
minutes, a sample of blood is withdrawn from the opposite arm. 1. Estimate blood volume.
This is to ensure there is no contamination of the sample from any 2. Estimate RBC volume at pre operative hematocrit.
isotope remaining at the injection site. The activity of this sample is 3. Estimate RBC volume at hematocrit 30% assuming
then measured and the dilution volume calculated from the result normal blood volume is maintained.
Repeated measurements can be made to estimate the change in 4. Calculate red cell volume lost when Hematocrit is 30%.
blood volume with allowance made for residual radio activity from 5. RBC volume lost =RBC preoperative — RBC volume 30%.
the previous measurements. 6. Allowable blood loss = RBC volume (lost) x 3
+ In a shocked patient, the time taken for mixing throughout the total
blood volume may be in excess of the 10-15 minutes usually Hemorrhagie Shock:
allowed, So the measurement is a better indication of the effective Gassl | Class | Claselll | ClassIV
circulating volume than it is of the total blood volume errors may
also arise from loss of the injected isotope by vigorous hemorthage Radios 150 7501500 | 15002009, | 22099
before mixing is complete. Pe or volume 15% 75-30% 30-40% 200%
‚Average blood volume. Pulserate <100 >100 >120 3140
Neonates: Premature 95 mi/kg, Full term 85 ml/kg, Infants 80 mag P Normal Normal] Decreased | Decreased
Mie Pulse‘ Decrease | Decrease | Decrease
+ Ideally blood loss should replace with crystalloid or colloid to nn u
maintain intravascular volume (normovolemia) until danger of a al =” Rosine! pe
anemia outweighs risks of transfusion. 9 (3 -
+ Atthat point further blood loss is replaced with transfusion of RBCs seconds)
to maintain Hb concentration or hematocrit at that level for most ee 1620 20:20 200 =
patients it corresponds to Hb between 7-8 g/d stes _
+ Hb <7gm/ dl > cardiac output t to maintain Oz delivery. ten output | 230 20:80 515 Negigible
. Her oom > for patients with cardiac / pulmonary disease / en Is meme | EE
Replace: tus &confused | lethargic
+ 1 mi of Blood = 3 mi crystalloid pad Grystalioid | Orystalaid | Crystalcid & | Crystalloid &
2 1 mi of Blood = 1 mi colloid replacement blood blood
+ Patients with normal hematocrit should generally be transfused
only after losses greater than 10-20% of their blood volume.
54
Dr Azam's Notes in Anesthesiology 2013
+ The activity remaining in the empty syringe is measured and Exact point Is based on patient's medical condition & surgical
deducted from the amount of the isotope injected. After 10-15 procedure.
minutes, a sample of blood is withdrawn from the opposite arm. 1. Estimate blood volume.
This is to ensure there is no contamination of the sample from any 2. Estimate RBC volume at pre operative hematocrit.
isotope remaining at the injection site. The activity of this sample is 3. Estimate RBC volume at hematocrit 30% assuming
then measured and the dilution volume calculated from the result normal blood volume is maintained.
Repeated measurements can be made to estimate the change in 4. Calculate red cell volume lost when Hematocrit is 30%.
blood volume with allowance made for residual radio activity from 5. RBC volume lost =RBC preoperative — RBC volume 30%.
the previous measurements. 6. Allowable blood loss = RBC volume (lost) x 3
+ In a shocked patient, the time taken for mixing throughout the total
blood volume may be in excess of the 10-15 minutes usually Hemorrhagie Shock:
allowed, So the measurement is a better indication of the effective Gassl | Class | Claselll | ClassIV
circulating volume than it is of the total blood volume errors may
also arise from loss of the injected isotope by vigorous hemorthage Radios 150 7501500 | 15002009, | 22099
before mixing is complete. Pe or volume 15% 75-30% 30-40% 200%
‚Average blood volume. Pulserate <100 >100 >120 3140
Neonates: Premature 95 mi/kg, Full term 85 ml/kg, Infants 80 mag P Normal Normal] Decreased | Decreased
Mie Pulse‘ Decrease | Decrease | Decrease
+ Ideally blood loss should replace with crystalloid or colloid to nn u
maintain intravascular volume (normovolemia) until danger of a al =” Rosine! pe
anemia outweighs risks of transfusion. 9 (3 -
+ Atthat point further blood loss is replaced with transfusion of RBCs seconds)
to maintain Hb concentration or hematocrit at that level for most ee 1620 20:20 200 =
patients it corresponds to Hb between 7-8 g/d stes _
+ Hb <7gm/ dl > cardiac output t to maintain Oz delivery. ten output | 230 20:80 515 Negigible
. Her oom > for patients with cardiac / pulmonary disease / en Is meme | EE
Replace: tus &confused | lethargic
+ 1 mi of Blood = 3 mi crystalloid pad Grystalioid | Orystalaid | Crystalcid & | Crystalloid &
2 1 mi of Blood = 1 mi colloid replacement blood blood
+ Patients with normal hematocrit should generally be transfused
only after losses greater than 10-20% of their blood volume.
54
Dr Azam's Notes in Anesthesiology 2013
23. Sickle Cell Anemia & Anesthesia
+ Sickle cell anemia was first noted clinically by
J.B. Herrick in 1904. in 1927 Hah and Gellespie
induced hypoxia and acidotic sickling and
incriminated haemoglobin as the cause, by
demonstrating them in ghost erythrocyte
+ Sickle cell disease is a hereditary
hemoglobinopathy in which the red cells contain
Hb-S instead of Hb-A. Hb-S differs from normal
adult Hb-A by the substitution of valine for
Glutamic acid at 8-6 of Hb molecule.
Types - Two Types
+ Sickle cell trait (heterozygous)
+ Sickle cell anemia (homozygous)
+ Sickle cell trait - asymptomatic carrier state for
Hb-S
+ Incidence in American blacks — 8-10%
+ RBC have Hb-S concentration < 50%
(38-4594)
+ Sickle cell anemia - incidence in American
blacks — 0.2%
+ RBC have Hb-S concentration 70-98%
+ Characterized by
= Chronic hemolysis
— Acute episodic vaso-occlusive crisis
+ Sickle cell crisis-Life threatening complication
in contrast to anemia
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Pathophysiology:
Low PaO:
fs
Deoxygenation of Hb-S.
1
Sickle shaped RBC
Sid Ho: has reacio sine
HoS molecules bind with each ther
Long aggregates tac (tigid, less soluble)
Increased viscosity of blood
E
Stasis of blood flow
4
Localized / generalized vascular occlusion
1
Infarction crisis
Vaso-occlusion common in liver and kidney where portal circulation PO; is usually
low.
Aplastic crisis - Characterized by bone marrow depression - cessation of
erythropoesis
N
Rapidly declining hematocrit Often associated with viral infection
Sequestration crisis -Is due to depletion of circulating RBC by virtue of
pooling of these cells in liver and spleen. Mainly affects children and infants —
may need immediate transfusion
Diagnosis -
1) Hb — 6-9gédl
+ Peripheral smear — normocytic normochromic anemia
2) Sickle test - Precipitation reaction
3) Sickle test
4) Haemoglobin electrophoresis - definitive test
55
+ Sickle cell anemia was first noted clinically by
J.B. Herrick in 1904. in 1927 Hah and Gellespie
induced hypoxia and acidotic sickling and
incriminated haemoglobin as the cause, by
demonstrating them in ghost erythrocyte
+ Sickle cell disease is a hereditary
hemoglobinopathy in which the red cells contain
Hb-S instead of Hb-A. Hb-S differs from normal
adult Hb-A by the substitution of valine for
Glutamic acid at 8-6 of Hb molecule.
Types - Two Types
+ Sickle cell trait (heterozygous)
+ Sickle cell anemia (homozygous)
+ Sickle cell trait - asymptomatic carrier state for
Hb-S
+ Incidence in American blacks — 8-10%
+ RBC have Hb-S concentration < 50%
(38-4594)
+ Sickle cell anemia - incidence in American
blacks — 0.2%
+ RBC have Hb-S concentration 70-98%
+ Characterized by
= Chronic hemolysis
— Acute episodic vaso-occlusive crisis
+ Sickle cell crisis-Life threatening complication
in contrast to anemia
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Pathophysiology:
Low PaO:
fs
Deoxygenation of Hb-S.
1
Sickle shaped RBC
Sid Ho: has reacio sine
HoS molecules bind with each ther
Long aggregates tac (tigid, less soluble)
Increased viscosity of blood
E
Stasis of blood flow
4
Localized / generalized vascular occlusion
1
Infarction crisis
Vaso-occlusion common in liver and kidney where portal circulation PO; is usually
low.
Aplastic crisis - Characterized by bone marrow depression - cessation of
erythropoesis
N
Rapidly declining hematocrit Often associated with viral infection
Sequestration crisis -Is due to depletion of circulating RBC by virtue of
pooling of these cells in liver and spleen. Mainly affects children and infants —
may need immediate transfusion
Diagnosis -
1) Hb — 6-9gédl
+ Peripheral smear — normocytic normochromic anemia
2) Sickle test - Precipitation reaction
3) Sickle test
4) Haemoglobin electrophoresis - definitive test
55
[Sickle Cell Anemia & Anesthesia. Continuation:
Treatment:
Principles of Treatment of sickle cell crisis
+ To keep the patient warm
+ To alleviate pain
+ To rehydrate
+ To treat infection, hypoxia, acidosis
+ Pain - Treatment with an opioid
+ The use of epidural analgesia using local anesthetic / opioid may be
useful if pain is in lower extremities.
+ Partial exchange transfusion — with fresh normal RBC Containing Hb-A-
leads to decreased HbS concentration
Goals:
+ To 1 HbA cone. To close to 50%
+ To keep hematocrit below 35%
+ Oral bicarbonate (up to 20 g/day) to produce mild Alkalization
Management of anesthesia
+ Pt with sickle cell trait — Not at increased risk during perioperative period
- Pt with sickle cell anemia — Increased risk
Orthopedic conditions are frequent in these patients.
+ Ex, Necrosis of head of femur, Leg ulcers, Gall stones, Priapism
FACTORS CAUSING SICKLING
1) Low PO2
In sickle cell anemia PaOz< 40 mm Hg
In sickle cell trait PaOz< 20 mm Hg
2) pH
Decreased pH — Acidosis - Favors sickling
Sickling - greater in veins than in arteries
3) Decreased body temperature
Exposure to cold - Vasoconstriction
4
Stasis of blood flow
4
Sickling
4)Dehydration - increases viscosity - stasis — sickling
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Clinical manifestations:
1. Those due to infarctive events due to occlusion of
blood vessels with sickle cells.
2. Those due to chronic hemolytic anemia (Hb 6-8 gril)
Infarctive events are responsible for wide spread organ
damage.
Cardiovascular system: Cor-pulmonale due to repeated
pulmonary emboli, and also, secondary to high output failure.
Central nervous system: Cerebrovascular accidents are
common especially in children. Stroke is significantly reduced
by transfusion programme of 2 units every fortnight. Stroke
may be induced by hyperventilation, severe anemia, infection,
sickle cell crisis
Respiratory system: Total Lung Capacity (TLC) and vital
capacity (VO) are frequently decreased. Pulmonary embolism
and respiratory infection are common in post operative period.
Genitourinary system: Renal abnormalities are established by
the age of five to either years. The hypertonic medulla
concentrates Hb and with its low oxygen partial pressure
promotes sickling, This produce papillary necrosis, hematuria
and inability to concentrate urine and renal failure, Priapism is
a common occurrence,
Hepatic and splenic infracts: May be focal or diffuse. Sever
liver dysfunction can result in pseudo-cholinesterase
deficiency.
Skeletal system: Aseptic necrosis of femoral head and
salmonella infection of small bones of the hand.
Treatment:
Principles of Treatment of sickle cell crisis
+ To keep the patient warm
+ To alleviate pain
+ To rehydrate
+ To treat infection, hypoxia, acidosis
+ Pain - Treatment with an opioid
+ The use of epidural analgesia using local anesthetic / opioid may be
useful if pain is in lower extremities.
+ Partial exchange transfusion — with fresh normal RBC Containing Hb-A-
leads to decreased HbS concentration
Goals:
+ To 1 HbA cone. To close to 50%
+ To keep hematocrit below 35%
+ Oral bicarbonate (up to 20 g/day) to produce mild Alkalization
Management of anesthesia
+ Pt with sickle cell trait — Not at increased risk during perioperative period
- Pt with sickle cell anemia — Increased risk
Orthopedic conditions are frequent in these patients.
+ Ex, Necrosis of head of femur, Leg ulcers, Gall stones, Priapism
FACTORS CAUSING SICKLING
1) Low PO2
In sickle cell anemia PaOz< 40 mm Hg
In sickle cell trait PaOz< 20 mm Hg
2) pH
Decreased pH — Acidosis - Favors sickling
Sickling - greater in veins than in arteries
3) Decreased body temperature
Exposure to cold - Vasoconstriction
4
Stasis of blood flow
4
Sickling
4)Dehydration - increases viscosity - stasis — sickling
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Clinical manifestations:
1. Those due to infarctive events due to occlusion of
blood vessels with sickle cells.
2. Those due to chronic hemolytic anemia (Hb 6-8 gril)
Infarctive events are responsible for wide spread organ
damage.
Cardiovascular system: Cor-pulmonale due to repeated
pulmonary emboli, and also, secondary to high output failure.
Central nervous system: Cerebrovascular accidents are
common especially in children. Stroke is significantly reduced
by transfusion programme of 2 units every fortnight. Stroke
may be induced by hyperventilation, severe anemia, infection,
sickle cell crisis
Respiratory system: Total Lung Capacity (TLC) and vital
capacity (VO) are frequently decreased. Pulmonary embolism
and respiratory infection are common in post operative period.
Genitourinary system: Renal abnormalities are established by
the age of five to either years. The hypertonic medulla
concentrates Hb and with its low oxygen partial pressure
promotes sickling, This produce papillary necrosis, hematuria
and inability to concentrate urine and renal failure, Priapism is
a common occurrence,
Hepatic and splenic infracts: May be focal or diffuse. Sever
liver dysfunction can result in pseudo-cholinesterase
deficiency.
Skeletal system: Aseptic necrosis of femoral head and
salmonella infection of small bones of the hand.
[Sickle Cell Anemia & Anesthesia. Continuation:
Chronic hemolysis of erythrocytes is reflected by:
1. Elevated levels of plasma bilirubin leading to cholelithiasis and
cholecystitis.
2. Periodic transfusion increases risk of viral hepatitis.
3. Hemochromatosis ensues with iron overload following repeated
transfusions. It leads to cirrhosis of liver and left ventricular
dysfunction also.
4. White cell function is depressed with increased susceptibility to
infection
Infarctive crisis:
This is triggered off by infection, trauma or associated
elevations in temperature. It is characterized by acute onset of pain
usually abdominal with fever and vomiting.
Treatment:
1. Adequate hydration.
2. Partial alkalization of blood
3. Partial exchange transfusion with erythrocyte containing
haemoglobin A.
4. Antibiotics.
In infants — splenomegaly children (6 yrs) - autosplenectomy.
Pre operative assessment and preparation:
Existing organ dysfunction should be assessed
Aggressive pre-operative hydration is essential
Prophylactic antibiotic cover.
Systemic preoperative alkalization which on one hand confers
an anti-sickling effect and on the other hand shifts the oxy-
Haemoglobin curve to left
Correction of co-existing infection.
Preoperative transfusion - Depend on severity of anemia and
magnitude of planned surgery
sopa
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Goals of preoperative RBC transfusion
1. To increase HbA conc. Close to 50%
2. To achieve hematocrit of 35%
Premedication:
+ Avoid drugs that causes respiratory depression.
+ Pre-oxygenate well; induction with thiopentone sodium and
succinyicholine followed by tracheal intubation and
controlled moderate hyperventilation with nitrous oxide and
‘oxygen. 30% oxygen is adequate and judicious doses of
halothane to promote vasodilatation
Intraoperative management
+ Avoidance of acidosis due to hypoventilation
+ Maintenance of optimal oxygenation
+ Prevention of circulatory stasis due to
- Improper body positioning
- Use of toumiquets
+ Maintenance of normal body temperature
+ Pre-oxygenate with high inspired Oz tension
+ Because to maintain normal to increased PaO2
Regional anesthesia preferred to G.A.
+ Administration of supplemental O2
+ Epidural / spinal - Produce compensatory vasoconstriction
and decreased PaOz in non blocked areas - sites of
infraction. There may be decrease in number of circulatory
sickle cells during and immediately after G.A.
Prevention of circulatory status requires.
- Maintenance of cardiovascular stability by adjustment
of depth of anesthesia.
Anticipation and Rapid correction of hypotension.
Maintenance of I.V. fluid volume by crystalloids
s7
Chronic hemolysis of erythrocytes is reflected by:
1. Elevated levels of plasma bilirubin leading to cholelithiasis and
cholecystitis.
2. Periodic transfusion increases risk of viral hepatitis.
3. Hemochromatosis ensues with iron overload following repeated
transfusions. It leads to cirrhosis of liver and left ventricular
dysfunction also.
4. White cell function is depressed with increased susceptibility to
infection
Infarctive crisis:
This is triggered off by infection, trauma or associated
elevations in temperature. It is characterized by acute onset of pain
usually abdominal with fever and vomiting.
Treatment:
1. Adequate hydration.
2. Partial alkalization of blood
3. Partial exchange transfusion with erythrocyte containing
haemoglobin A.
4. Antibiotics.
In infants — splenomegaly children (6 yrs) - autosplenectomy.
Pre operative assessment and preparation:
Existing organ dysfunction should be assessed
Aggressive pre-operative hydration is essential
Prophylactic antibiotic cover.
Systemic preoperative alkalization which on one hand confers
an anti-sickling effect and on the other hand shifts the oxy-
Haemoglobin curve to left
Correction of co-existing infection.
Preoperative transfusion - Depend on severity of anemia and
magnitude of planned surgery
sopa
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Goals of preoperative RBC transfusion
1. To increase HbA conc. Close to 50%
2. To achieve hematocrit of 35%
Premedication:
+ Avoid drugs that causes respiratory depression.
+ Pre-oxygenate well; induction with thiopentone sodium and
succinyicholine followed by tracheal intubation and
controlled moderate hyperventilation with nitrous oxide and
‘oxygen. 30% oxygen is adequate and judicious doses of
halothane to promote vasodilatation
Intraoperative management
+ Avoidance of acidosis due to hypoventilation
+ Maintenance of optimal oxygenation
+ Prevention of circulatory stasis due to
- Improper body positioning
- Use of toumiquets
+ Maintenance of normal body temperature
+ Pre-oxygenate with high inspired Oz tension
+ Because to maintain normal to increased PaO2
Regional anesthesia preferred to G.A.
+ Administration of supplemental O2
+ Epidural / spinal - Produce compensatory vasoconstriction
and decreased PaOz in non blocked areas - sites of
infraction. There may be decrease in number of circulatory
sickle cells during and immediately after G.A.
Prevention of circulatory status requires.
- Maintenance of cardiovascular stability by adjustment
of depth of anesthesia.
Anticipation and Rapid correction of hypotension.
Maintenance of I.V. fluid volume by crystalloids
s7
[Sickle Cell Anemia & Anesthesia. Continuation: Dr Azam's Notes in Anesthesiology 2013
Post operative management: Post operative period:
+ Continue oxygenation up to 8 hrs.
+ Early mobilization of patient.
+ Chest physiotherapy.
+ Adequate antibiotic cover to control chest infection.
+ Careful watch for infarction crisis; bone pain usually heralds bone
infarcts. Heparin and Magnesium Sulfate should be given immediately.
+ Maintenance of intravascular volume
Dr Azam's Notes in Anesthesiology 2013
Post operative management: Post operative period:
+ Continue oxygenation up to 8 hrs.
+ Early mobilization of patient.
+ Chest physiotherapy.
+ Adequate antibiotic cover to control chest infection.
+ Careful watch for infarction crisis; bone pain usually heralds bone
infarcts. Heparin and Magnesium Sulfate should be given immediately.
+ Maintenance of intravascular volume
Dr Azam's Notes in Anesthesiology 2013
24. Anemia & Anesthesia,
Definition:
Anemia is a condition in which there, is
decreased oxygen carrying capacity of the
blood, because of reduced concentration of
haemoglobin in the presence of a normal or
near normal blood volume for the age and sex
of the individual. It is not a primary disease but
a manifestation of some other underlying
disease.
Normal haemoglobin levels:
+ Men = 13 - 18 g/dl
+ Women = 11.5 - 16.5 gidl
+ Full term infant = 13.5 — 19.5 g/dl
- Children = 11-14 g/dl
+ In India, usually Hb concentration of less
than 10 gidl is taken is anemia.
Etiology and classification of anemia:
Classification:
+ Pathophyslological
+ Etiological
Dr Azam's Notes in Anesthesiology 2013
People Classification
y
1) Blood loss
AJ Acute
Ex. Trauma
8) Chronic
Ex. Peptic ulcer
menorrhaain
y y
1) Impaired RBC production 11) Excessive RBC destruction
A) Nutritional A) Intrinsic defects in RBC
a) Iron deficiency a) RBC membrane defects.
b) Vitamin B,, and folic acid Ex:H. Spherocytosis
deficiency H. Elliptocytosis
© Protein energy malnutrition) RBCenzyme deficiency
B) Depression of erythropoeisis Ex: G6PD deficiency
a) Chronic disorders ©) Disorder of Hb synthesis
Ex Infection Ex: Sickle cell anemia thalassaemia
- TB B. Extrinsic effect on RBC
- Costeomyelttis a) Antibody mediated
Rheumatoid arthritis Ex. Transfusion reaction
b) Chronic renal failure Autoantibodies > SLE, Drugs
©) Aplastic anemia b) Infection > Malaria
d) Malignancies €) Chemical - lead poisoning
Ex. Leukemia
‘Myeloma
Morphological classification
y
Normocytic normochromic
Ex: Blood loss
- Hemolytic
- Aplastic
- Chronic renal failure
- Anemia or chronic
infection
Dr Azam's Notes in Anesthesiology 2013
y y
MICROCYTIC Macrocytic anemia
HYPOCHROMIC Ex: Megaloblastic anemia
Ex. Iron deficiency anemia
- Thalassaemia
- Sideroblastic anemia
Definition:
Anemia is a condition in which there, is
decreased oxygen carrying capacity of the
blood, because of reduced concentration of
haemoglobin in the presence of a normal or
near normal blood volume for the age and sex
of the individual. It is not a primary disease but
a manifestation of some other underlying
disease.
Normal haemoglobin levels:
+ Men = 13 - 18 g/dl
+ Women = 11.5 - 16.5 gidl
+ Full term infant = 13.5 — 19.5 g/dl
- Children = 11-14 g/dl
+ In India, usually Hb concentration of less
than 10 gidl is taken is anemia.
Etiology and classification of anemia:
Classification:
+ Pathophyslological
+ Etiological
Dr Azam's Notes in Anesthesiology 2013
People Classification
y
1) Blood loss
AJ Acute
Ex. Trauma
8) Chronic
Ex. Peptic ulcer
menorrhaain
y y
1) Impaired RBC production 11) Excessive RBC destruction
A) Nutritional A) Intrinsic defects in RBC
a) Iron deficiency a) RBC membrane defects.
b) Vitamin B,, and folic acid Ex:H. Spherocytosis
deficiency H. Elliptocytosis
© Protein energy malnutrition) RBCenzyme deficiency
B) Depression of erythropoeisis Ex: G6PD deficiency
a) Chronic disorders ©) Disorder of Hb synthesis
Ex Infection Ex: Sickle cell anemia thalassaemia
- TB B. Extrinsic effect on RBC
- Costeomyelttis a) Antibody mediated
Rheumatoid arthritis Ex. Transfusion reaction
b) Chronic renal failure Autoantibodies > SLE, Drugs
©) Aplastic anemia b) Infection > Malaria
d) Malignancies €) Chemical - lead poisoning
Ex. Leukemia
‘Myeloma
Morphological classification
y
Normocytic normochromic
Ex: Blood loss
- Hemolytic
- Aplastic
- Chronic renal failure
- Anemia or chronic
infection
Dr Azam's Notes in Anesthesiology 2013
y y
MICROCYTIC Macrocytic anemia
HYPOCHROMIC Ex: Megaloblastic anemia
Ex. Iron deficiency anemia
- Thalassaemia
- Sideroblastic anemia
[Anemia & Anesthesla.Continuation:
Compensatory mechanisms In anemia:
1. Increased blood flow to the tissues (Decreased Viscosity, increased
Cardiac output & redistribution of tissue blood Flow):
Decreased blood viscosity
Fall in peripheral Vascular resistance
Increased blood fow in microcirculation
Increased — return
Increased can output
Il. Oz transport capacity is 100% at hematocrit of 40% but physiological
supply of O to tissues is optimum at hematocrit of 30%
111, Redistribution of tissue blood flow in metabolically active tissue >
+Brought about by
1. Auto-regulation
2. By input from autonomic nervous system
3. Increased cardiac output
4. Increased tissue oxygen extraction
Effect of anemia on myocardial 02 consumption:
Ata Hematocrit of 20-25%.
y
Tachycardia and increased contractility
y
+ Increased cardiovascular work and increased O2 demand by the heart
+ Heart: 1 Oz extraction normal 65-70% in heart, 1 coronary blood flow
+ In anemia O extraction quickly reaches maximum. C.O doubled (2
times), CBF trebled (3 times)
+ In healthy persons — if Hb decreases by 50%
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Clinical features of anemia
[mite Moderate Bevere
[Asymptomatic [Dyspnoea on exertion Dyspnoea at rest
Tiredness alpitations gina pectoris in older]
Weakness iddiness tients
Easy fatigability [Tinnitus murmurs
Lassitude pots before eye ardiomegaly
norexia 'ongestive cardiac
K of concentration Failure
VP
dema
ligh output state
(Collapsing pulse)
Jouding of conscious
ollonychias
1. Haemoglobin > decreased
2. RBC count > decreased (N > 4.5 - 5.5 million /mm)
3. Total WBC count > increased if infection
4. Differential count
5, Peripheral smear:
1.D.A Megaloblastic ‘Aplastic
IMicrocytic Macrocytic REC Normocytic
ypochromic Hypersegmented Normochromic
Krane Neutrophils eucopenia
Poikilocytosis hrombocytopenia
Compensatory mechanisms In anemia:
1. Increased blood flow to the tissues (Decreased Viscosity, increased
Cardiac output & redistribution of tissue blood Flow):
Decreased blood viscosity
Fall in peripheral Vascular resistance
Increased blood fow in microcirculation
Increased — return
Increased can output
Il. Oz transport capacity is 100% at hematocrit of 40% but physiological
supply of O to tissues is optimum at hematocrit of 30%
111, Redistribution of tissue blood flow in metabolically active tissue >
+Brought about by
1. Auto-regulation
2. By input from autonomic nervous system
3. Increased cardiac output
4. Increased tissue oxygen extraction
Effect of anemia on myocardial 02 consumption:
Ata Hematocrit of 20-25%.
y
Tachycardia and increased contractility
y
+ Increased cardiovascular work and increased O2 demand by the heart
+ Heart: 1 Oz extraction normal 65-70% in heart, 1 coronary blood flow
+ In anemia O extraction quickly reaches maximum. C.O doubled (2
times), CBF trebled (3 times)
+ In healthy persons — if Hb decreases by 50%
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Clinical features of anemia
[mite Moderate Bevere
[Asymptomatic [Dyspnoea on exertion Dyspnoea at rest
Tiredness alpitations gina pectoris in older]
Weakness iddiness tients
Easy fatigability [Tinnitus murmurs
Lassitude pots before eye ardiomegaly
norexia 'ongestive cardiac
K of concentration Failure
VP
dema
ligh output state
(Collapsing pulse)
Jouding of conscious
ollonychias
1. Haemoglobin > decreased
2. RBC count > decreased (N > 4.5 - 5.5 million /mm)
3. Total WBC count > increased if infection
4. Differential count
5, Peripheral smear:
1.D.A Megaloblastic ‘Aplastic
IMicrocytic Macrocytic REC Normocytic
ypochromic Hypersegmented Normochromic
Krane Neutrophils eucopenia
Poikilocytosis hrombocytopenia
[Anemia & Anesthesla.Continuation:
6. Red cell indices:
+ MCV = PCV/RBC Count
+ Normal 75 to 100 femtoliters (fl)
+ tmegaloblastic
+ Jin
IDA
+ MCH = total Hb/RBC count
+ Normal 24- 33 pg
+ {IDA
+ MCHC = Total Hb/PCV
Normal 30 -36 g/dl
Blood | Normal | FeDef. | Folate/
Indices B12 Def
mov) [75-100 |<75 140/110
MCH (pg) [24-33 | <25 33/40
MCHC(%) | 30-36 | <30 32/88
+ Blochemical INV Megaloblastic IDA
Serum iron Serum vitamin Biz assay
T.LB.C. Serum folate assay
8. ferritin Schilling test
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
VI) Anesthetic management:
Preoperative evaluation:
1) To search for cause and correction of anemia
2) To assess the nature and degree of compensation/
3) To evaluate the amount of reserve available for intraoperative
compensation.
+ History > weakness / dyspnoea / palpitation / chronic blood loss / jaundice /
parasthesia / smoking / pain abdomen.
+ Examination > Build, nourishment, pallor, icterus, GPE oedema, clubbing,
lymphadenopathy.
+ Pulse, B.P. UVP, Shift of apex beat.
+ CVS > Tachycardia, apex beat, auscultate for murmur in L* 2° ICs,
cardiomegaly, carotid bruit
+ RS. > Breath sounds infections.
+ PA > Organomegaly > Liver, spleen
+ LAB INV > Hb%, TC, D.C, peripheral smear.
+ BU, S.Creatinine, S/Bilirubin, ECG, CXR, urine — routine
+ Elective surgery: Major surgeries postponed and treated with iron, vitamin
Bra, folic acid if Hb <7 gid
- Blood transfusion considered it should be completed 48 hrs prior to surgery.
+ Packed RBC preferred to whole blood.
+ Transfusion of RBC > to tO2 carrying capacity, not for volume expansion:
+ Fresh blood preferred to stored blood (2, 3 DPG less) transfusion of 1 unit
whole blood > increases Hb by 1 gidl/ Hct by 3%.
+ Packed RBC produce twice increase in Hb compared to whole blood basis for
decision for preoperative transfusion > duration and etiology of anemia
intravascular fluid volume urgency of surgery.
- Likely blood loss co-existing diseases > myocardial ischemia, lung disease,
cerebrovascular disease.
+ Emergency surgery: No time to correct anemia patient scheduled for surgery
without delay.
+ Premedication > Benzodiazepines — Ex: Diazepam 0.01-0.2 mg/kg.
+ Narcotic drugs low dose (because Respiratory depression) avoid atropine.
si
6. Red cell indices:
+ MCV = PCV/RBC Count
+ Normal 75 to 100 femtoliters (fl)
+ tmegaloblastic
+ Jin
IDA
+ MCH = total Hb/RBC count
+ Normal 24- 33 pg
+ {IDA
+ MCHC = Total Hb/PCV
Normal 30 -36 g/dl
Blood | Normal | FeDef. | Folate/
Indices B12 Def
mov) [75-100 |<75 140/110
MCH (pg) [24-33 | <25 33/40
MCHC(%) | 30-36 | <30 32/88
+ Blochemical INV Megaloblastic IDA
Serum iron Serum vitamin Biz assay
T.LB.C. Serum folate assay
8. ferritin Schilling test
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
VI) Anesthetic management:
Preoperative evaluation:
1) To search for cause and correction of anemia
2) To assess the nature and degree of compensation/
3) To evaluate the amount of reserve available for intraoperative
compensation.
+ History > weakness / dyspnoea / palpitation / chronic blood loss / jaundice /
parasthesia / smoking / pain abdomen.
+ Examination > Build, nourishment, pallor, icterus, GPE oedema, clubbing,
lymphadenopathy.
+ Pulse, B.P. UVP, Shift of apex beat.
+ CVS > Tachycardia, apex beat, auscultate for murmur in L* 2° ICs,
cardiomegaly, carotid bruit
+ RS. > Breath sounds infections.
+ PA > Organomegaly > Liver, spleen
+ LAB INV > Hb%, TC, D.C, peripheral smear.
+ BU, S.Creatinine, S/Bilirubin, ECG, CXR, urine — routine
+ Elective surgery: Major surgeries postponed and treated with iron, vitamin
Bra, folic acid if Hb <7 gid
- Blood transfusion considered it should be completed 48 hrs prior to surgery.
+ Packed RBC preferred to whole blood.
+ Transfusion of RBC > to tO2 carrying capacity, not for volume expansion:
+ Fresh blood preferred to stored blood (2, 3 DPG less) transfusion of 1 unit
whole blood > increases Hb by 1 gidl/ Hct by 3%.
+ Packed RBC produce twice increase in Hb compared to whole blood basis for
decision for preoperative transfusion > duration and etiology of anemia
intravascular fluid volume urgency of surgery.
- Likely blood loss co-existing diseases > myocardial ischemia, lung disease,
cerebrovascular disease.
+ Emergency surgery: No time to correct anemia patient scheduled for surgery
without delay.
+ Premedication > Benzodiazepines — Ex: Diazepam 0.01-0.2 mg/kg.
+ Narcotic drugs low dose (because Respiratory depression) avoid atropine.
si
[Anemia & Anesthesla.Continuation:
Aim: To minimize significant changes which interfere with O2
delivery. To tissues.
Inspired Oz tension > adequate > for full saturation
Avoid all drugs which induce fall in cardiac output
Avoid a shift to left of ODC > Eg. Hyperventilation
Careful positioning > avoid peripheral pooling
Quick blood transfusion
Slow and smooth induction
Use of tourniquet > to | operative blood loss
Avoid hypothermia, acidosis, hypoxia and dehydration
ENOTES
Monitoring:
+ Pulse,
+ BP.
+ pulse oximetry
+ ECG,
+ ABG,
+ CP,
+ urine output.
Regional anesthesia
+ Spinal if patient is normovolaemic & has no tachycardia,
precaution during preloading, epidural anesthesia
preferred to spinal, local blocks preferred for limb surgery
supplement with Oz and adequate sedation.
+ Avoid regional blocks if Hb < 8 gm/dl
+ Avoid regional anesthesia in megaloblastic anemia with
neurological changes.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
General anesthesia:
Preoxygenation:
+ Using high FIO2 (100%).
- To optimize PaO>
Induction:
+ If normovolemic > propofol > 1.5 - 2.5 mg/kg , thiopentone 3-5 mg/kg
for intubation > scoline 1-2 mg/kg midazolam > 0.1 — 0.3 mg/kg.
+ Maintenance > with very low levels of inhalational anesthetic s (because
depression of myocardial). Less soluble in plasma of anemic patient (|
lipid rich RBC)
Nitrous oxide avoided in megaloblastic and aplastic anemi
+ Oxygen > FiO2- 50%
+ Controlled ventilation with non depolarizing relaxant.
+ Vecuronium + cardiostable avoid drug causing tachycardia like
pancuronium
+ Extubation > after complete reversal and fully awake patient
glycopyrrolate preferred to atropine.
Postoperative management:
+ Avoidance of hypoxemia > O2 given in first 24 hr with FiO2 30-50%
+ Avoidance of hypovolemia > correct with blood transfusion,
erystalloids 3:1, colloids 1:1
+ Avoidance of hypothermia, hyperthermia, convulsion.
+ Affect Oe supply / demand ratio. Patient kept warm.
+ To avoid shivering
+ Avoidance of pain, as pain > tachycardia > increased O2 demand >
adequate postoperative analgesia.
+ N2O inhibits the activity of methionine synthetase by oxidizing the
cobalt atom of vitamin Biz from an active to inactive state.
+ Even relatively short exposures to N20 may produce megaloblastic
changes methionine synthetase is needed for cell division.
Aim: To minimize significant changes which interfere with O2
delivery. To tissues.
Inspired Oz tension > adequate > for full saturation
Avoid all drugs which induce fall in cardiac output
Avoid a shift to left of ODC > Eg. Hyperventilation
Careful positioning > avoid peripheral pooling
Quick blood transfusion
Slow and smooth induction
Use of tourniquet > to | operative blood loss
Avoid hypothermia, acidosis, hypoxia and dehydration
ENOTES
Monitoring:
+ Pulse,
+ BP.
+ pulse oximetry
+ ECG,
+ ABG,
+ CP,
+ urine output.
Regional anesthesia
+ Spinal if patient is normovolaemic & has no tachycardia,
precaution during preloading, epidural anesthesia
preferred to spinal, local blocks preferred for limb surgery
supplement with Oz and adequate sedation.
+ Avoid regional blocks if Hb < 8 gm/dl
+ Avoid regional anesthesia in megaloblastic anemia with
neurological changes.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
General anesthesia:
Preoxygenation:
+ Using high FIO2 (100%).
- To optimize PaO>
Induction:
+ If normovolemic > propofol > 1.5 - 2.5 mg/kg , thiopentone 3-5 mg/kg
for intubation > scoline 1-2 mg/kg midazolam > 0.1 — 0.3 mg/kg.
+ Maintenance > with very low levels of inhalational anesthetic s (because
depression of myocardial). Less soluble in plasma of anemic patient (|
lipid rich RBC)
Nitrous oxide avoided in megaloblastic and aplastic anemi
+ Oxygen > FiO2- 50%
+ Controlled ventilation with non depolarizing relaxant.
+ Vecuronium + cardiostable avoid drug causing tachycardia like
pancuronium
+ Extubation > after complete reversal and fully awake patient
glycopyrrolate preferred to atropine.
Postoperative management:
+ Avoidance of hypoxemia > O2 given in first 24 hr with FiO2 30-50%
+ Avoidance of hypovolemia > correct with blood transfusion,
erystalloids 3:1, colloids 1:1
+ Avoidance of hypothermia, hyperthermia, convulsion.
+ Affect Oe supply / demand ratio. Patient kept warm.
+ To avoid shivering
+ Avoidance of pain, as pain > tachycardia > increased O2 demand >
adequate postoperative analgesia.
+ N2O inhibits the activity of methionine synthetase by oxidizing the
cobalt atom of vitamin Biz from an active to inactive state.
+ Even relatively short exposures to N20 may produce megaloblastic
changes methionine synthetase is needed for cell division.
24. Autologous Blood transfusion]
+ Autologous blood transfusion is one in which both donor as
well as recipient are the same.
+ There are 4 types of autologous transfusion. The
advantages and disadvantages, applications and
complications vary with the techniques being used. It is often
appropriate to employ more than one technique for patients
undergoing surgical procedures associated with significant
blood loss.
‘Types of autologous blood transfusion:
|. Preoperative blood donation
Il, Intraoperative blood salvage
Ill, Postoperative blood salvage
IV. Isovolumic haemadilution
|, PREOPERATIVE BLOOD DONATION:
+ In suitable cases, approx. 70% of patients can have their
total surgical blood requirement satisfied using pre-
deposited donation.
i) Patient selection:
+ The criteria for pre-deposited donations are less strict than
those for normal homologous blood donors. The
haemoglobin concentration should normally be greater than
11gmíd and never below 10gm/dl.
ii)Contraindications:
Act bacterial infection
cardiac disease
loss of consciousness
Impaired placenta blood low —HTN, PET, OM
Active bacterial infection:
+ Patients who have active infections septic, if such blood is
drawn, the bacteria may proliferate during storage, leading
to fatal reactions.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Patients with cardiac disease:
Absolute contraindications to pre-deposited are
Significant aortic stenosis
prolonged and / or frequent unstable angina
Significant narrowing of the left main coronary artery.
Cyanotic heart disease
. Uncontrolled hypotension
Loss of consciousness:
+ Patients who have previously been blood donors and have had a
prolonged fainting attack should not be accepted.
Impaired placental blood flow:
+ Pregnant patients should not pre-donate if they are suffering from a
disease, such as hypertension; pre-eclamptic toxemia or diabetes
mellitus, which is associated with impaired placental flow and /or
intrauterine growth retardation.
ora.
Method:
+ Patients can donate 450m! of blood at weekly intervals; the last
donation being at-least 4 days and preferably 1 week prior to surgery.
+ They should commence oral iron prior to their first donation and
continue until the day of surgery. Adults weighing less than 50kg and
pediatric patients require special consideration.
+ The volume withdrawn at any one time should not exceed 12 percent of
the Pts estimated blood volume.
+ They should have blood drawn into pedipack containing 35m of
anticoagulant and which are suitable for collection of up to 250ml of
blood
The physiological response in patients taking B-blockers and / or ACE
inhibitors is compromised by their treatment, they should therefore be
given isovolumic crystalloid replacement to minimize the hazardous
sequelae, which may follow a sudden reduction in blood volume, when
donating late in pregnancy; patients should be in the lateral position
because of the weight of the uterus impedes the venous return when
the patients is lying on her back.
+ Autologous blood transfusion is one in which both donor as
well as recipient are the same.
+ There are 4 types of autologous transfusion. The
advantages and disadvantages, applications and
complications vary with the techniques being used. It is often
appropriate to employ more than one technique for patients
undergoing surgical procedures associated with significant
blood loss.
‘Types of autologous blood transfusion:
|. Preoperative blood donation
Il, Intraoperative blood salvage
Ill, Postoperative blood salvage
IV. Isovolumic haemadilution
|, PREOPERATIVE BLOOD DONATION:
+ In suitable cases, approx. 70% of patients can have their
total surgical blood requirement satisfied using pre-
deposited donation.
i) Patient selection:
+ The criteria for pre-deposited donations are less strict than
those for normal homologous blood donors. The
haemoglobin concentration should normally be greater than
11gmíd and never below 10gm/dl.
ii)Contraindications:
Act bacterial infection
cardiac disease
loss of consciousness
Impaired placenta blood low —HTN, PET, OM
Active bacterial infection:
+ Patients who have active infections septic, if such blood is
drawn, the bacteria may proliferate during storage, leading
to fatal reactions.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Patients with cardiac disease:
Absolute contraindications to pre-deposited are
Significant aortic stenosis
prolonged and / or frequent unstable angina
Significant narrowing of the left main coronary artery.
Cyanotic heart disease
. Uncontrolled hypotension
Loss of consciousness:
+ Patients who have previously been blood donors and have had a
prolonged fainting attack should not be accepted.
Impaired placental blood flow:
+ Pregnant patients should not pre-donate if they are suffering from a
disease, such as hypertension; pre-eclamptic toxemia or diabetes
mellitus, which is associated with impaired placental flow and /or
intrauterine growth retardation.
ora.
Method:
+ Patients can donate 450m! of blood at weekly intervals; the last
donation being at-least 4 days and preferably 1 week prior to surgery.
+ They should commence oral iron prior to their first donation and
continue until the day of surgery. Adults weighing less than 50kg and
pediatric patients require special consideration.
+ The volume withdrawn at any one time should not exceed 12 percent of
the Pts estimated blood volume.
+ They should have blood drawn into pedipack containing 35m of
anticoagulant and which are suitable for collection of up to 250ml of
blood
The physiological response in patients taking B-blockers and / or ACE
inhibitors is compromised by their treatment, they should therefore be
given isovolumic crystalloid replacement to minimize the hazardous
sequelae, which may follow a sudden reduction in blood volume, when
donating late in pregnancy; patients should be in the lateral position
because of the weight of the uterus impedes the venous return when
the patients is lying on her back.
[Autologous Blood transfusion.Continuation:
INTRAOPERATIVE BLOOD SALVAGE:
+ Pre-deposit donation is limited by the time that the blood can
be stored and by the ability of patients to donate at frequent
intervals. Isovolumic hemodilution or acute normovolemic
hemodilution (ANH) is limited by the patients total blood
volume and by hemodynamic considerations. Postoperative
salvage is limited by mechanical problems and possible
bacterial contamination intraoperative cell salvage (ICS) in
contrast, can be used throughout the surgical procedure and
is able to replace blood in proportion to the amount lost.
Methods and equipment:
+ The basis of ICS is to collect shed blood from the operative
field; into a sterile container where the blood may or may not
be further processed; prior to retuming it to the patient, To
prevent the blood clotting; either the patient has to be
anticoagulated prior to the operation, or anticoagulant has to
be added to the blood at the sucker tip. Anticoagulation
cannot be delayed until the blood has arrived in the container
because, unlike the situation in normal blood donation, the
coagulation factors have been activated in the operative
field
The main steps of this technique are
1. Salvaging the blood from the operative site.
2. Anti-coagulating the whole blood - prior to surgery during
suction.
3. Re-infusing whole blood as such after filtering or re-infusing
the red cells after washing
There are three basic methods for ICs:
|. Semi continuous flow centrifugation
I. Canister collection
111. Single use disposable reservoirs
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
1) Disposable reservoirs: Shed blood is aspirated using a vacuum
pressure of less than 150mm Hg into a single- use self contained
disposable reservoir. Unless the patient has been anticoagulated prior to
surgery, the blood should be anticoagulated using citrate. When the
reservoir is full, the blood can either be immediately re-infused by gravity
using a standard given set and microaggregate filter, or stored until room
temperature, until required.
Advantage — being cheap and requiring no specialized equipment or
specially trained personnel.
Disadvantage — slow, only suitable for small volumes and the product is
unwashed and has a low hematocrit.
2) Canister collection: The blood is aspirated, via a double lumen sucker
that allows anticoagulant to be mixed at the sucker tip, through a 170um
filter into a rigid reservoir containing a disposable liner. When the canister
is full, the liner is removed and the blood re-infused through a standard
transfusion set and microaggregate filter. Prior to reinfusion the blood can
be washed using a standard cell washer which is usually situated in the
blood bank.
3) Semi continuous flow centrifugation: Blood is aspirated, using a double
lumen sucker, into a reservoir. The blood is washed, with saline prior to
being re-infused. There are two varieties of equipment available, the so
called slow flow machines which produce one unit every 7-10 mins and
the fast flow system which produce a unit in less than 3 mins.
To avoid hemolysis the following precautions should be taken
1. Blood should be aspirated by placing the tip below the surface of the
blood. The surgeon must avoid skimming, as aspiration of air with the
blood will lead to turbulence and hemolysis.
2. The sucker should have a plastic tip with multiple holes. This is
especially important during orthopedic surgery as aspirated debris
may occlude some of the holes, thereby increasing turbulence.
INTRAOPERATIVE BLOOD SALVAGE:
+ Pre-deposit donation is limited by the time that the blood can
be stored and by the ability of patients to donate at frequent
intervals. Isovolumic hemodilution or acute normovolemic
hemodilution (ANH) is limited by the patients total blood
volume and by hemodynamic considerations. Postoperative
salvage is limited by mechanical problems and possible
bacterial contamination intraoperative cell salvage (ICS) in
contrast, can be used throughout the surgical procedure and
is able to replace blood in proportion to the amount lost.
Methods and equipment:
+ The basis of ICS is to collect shed blood from the operative
field; into a sterile container where the blood may or may not
be further processed; prior to retuming it to the patient, To
prevent the blood clotting; either the patient has to be
anticoagulated prior to the operation, or anticoagulant has to
be added to the blood at the sucker tip. Anticoagulation
cannot be delayed until the blood has arrived in the container
because, unlike the situation in normal blood donation, the
coagulation factors have been activated in the operative
field
The main steps of this technique are
1. Salvaging the blood from the operative site.
2. Anti-coagulating the whole blood - prior to surgery during
suction.
3. Re-infusing whole blood as such after filtering or re-infusing
the red cells after washing
There are three basic methods for ICs:
|. Semi continuous flow centrifugation
I. Canister collection
111. Single use disposable reservoirs
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
1) Disposable reservoirs: Shed blood is aspirated using a vacuum
pressure of less than 150mm Hg into a single- use self contained
disposable reservoir. Unless the patient has been anticoagulated prior to
surgery, the blood should be anticoagulated using citrate. When the
reservoir is full, the blood can either be immediately re-infused by gravity
using a standard given set and microaggregate filter, or stored until room
temperature, until required.
Advantage — being cheap and requiring no specialized equipment or
specially trained personnel.
Disadvantage — slow, only suitable for small volumes and the product is
unwashed and has a low hematocrit.
2) Canister collection: The blood is aspirated, via a double lumen sucker
that allows anticoagulant to be mixed at the sucker tip, through a 170um
filter into a rigid reservoir containing a disposable liner. When the canister
is full, the liner is removed and the blood re-infused through a standard
transfusion set and microaggregate filter. Prior to reinfusion the blood can
be washed using a standard cell washer which is usually situated in the
blood bank.
3) Semi continuous flow centrifugation: Blood is aspirated, using a double
lumen sucker, into a reservoir. The blood is washed, with saline prior to
being re-infused. There are two varieties of equipment available, the so
called slow flow machines which produce one unit every 7-10 mins and
the fast flow system which produce a unit in less than 3 mins.
To avoid hemolysis the following precautions should be taken
1. Blood should be aspirated by placing the tip below the surface of the
blood. The surgeon must avoid skimming, as aspiration of air with the
blood will lead to turbulence and hemolysis.
2. The sucker should have a plastic tip with multiple holes. This is
especially important during orthopedic surgery as aspirated debris
may occlude some of the holes, thereby increasing turbulence.
[Autologous Blood transfusion.Continuation:
Base Cavoor OF Born Sxrems
un Fe
Ri
sy
Dr Azam's Notes in Anesthesiology 2013
Dr Azamı's Notes in Anesthesiology 2013
Anticoagulant:
+ Citrate in a ratio of 1:5 to 1:1, or heparin at a concentration of 30,000
units per It of saline, with 15m! of heparin / saline being added to each
100 mi of blood (ratio heparin to blood, 1:7).
Wash solution:
+ The volume of saline wash solution should be three to four times that of
the volume of the blood, although for orthopedic cases this may be
increased to six to seven times with a minimum volume of 150ml
Re-infusion:
+ The blood must be re-infused using a standard blood filter with or
without a microaggregate filter.
INDICATIONS FOR INTRAOPERATIVE CELL SALVAGE:
1) Cardiovascular:
+ The canister collection method should be used when the anticipated
blood loss is less than 1500ml when greater loss is expected, a semi
continuous flow centrifugal method is preferred.
2) Vascular surgery:
+ Both in the reconstruction of an aortic aneurysm and in the treatment of
aortic rupture there is requirement for rapid salvage and returns of
blood. In these cases, fast flow instruments are usually best
3) Orthopedic: Hip and spinal surgery
+ In hip and spinal surgery, the use of ICS, especially when combined
with pre-deposit elevation can usually avoid the need for homologous
blood
4) Liver transplantation
5) Neurosurgery - AVM: ICS is used during the refashioning of
arteriovenous malformations,
65
Base Cavoor OF Born Sxrems
un Fe
Ri
sy
Dr Azam's Notes in Anesthesiology 2013
Dr Azamı's Notes in Anesthesiology 2013
Anticoagulant:
+ Citrate in a ratio of 1:5 to 1:1, or heparin at a concentration of 30,000
units per It of saline, with 15m! of heparin / saline being added to each
100 mi of blood (ratio heparin to blood, 1:7).
Wash solution:
+ The volume of saline wash solution should be three to four times that of
the volume of the blood, although for orthopedic cases this may be
increased to six to seven times with a minimum volume of 150ml
Re-infusion:
+ The blood must be re-infused using a standard blood filter with or
without a microaggregate filter.
INDICATIONS FOR INTRAOPERATIVE CELL SALVAGE:
1) Cardiovascular:
+ The canister collection method should be used when the anticipated
blood loss is less than 1500ml when greater loss is expected, a semi
continuous flow centrifugal method is preferred.
2) Vascular surgery:
+ Both in the reconstruction of an aortic aneurysm and in the treatment of
aortic rupture there is requirement for rapid salvage and returns of
blood. In these cases, fast flow instruments are usually best
3) Orthopedic: Hip and spinal surgery
+ In hip and spinal surgery, the use of ICS, especially when combined
with pre-deposit elevation can usually avoid the need for homologous
blood
4) Liver transplantation
5) Neurosurgery - AVM: ICS is used during the refashioning of
arteriovenous malformations,
65
[Autologous Blood transfusion.Continuation:
6) Trauma
7) Ectopic pregnancy:
+ Thorough washing of the blood is required to prevent the
reinfusion of amniotic fluid leading to emboli and DIC.
8) Plastic surgery
9) Jehovah's witnesses
10) Serological antibodies:
+ Patients with rare and / or multiple serological antibodies
and / or other cross-match problems can be candidates for
ICs.
Contraindications:
1. Retrieval of blood from infective sites and from abdomen
with fecal soiling is to be avoided. This should be done only
as a last resort as it carries a high risk of bacteremia and
septicemia. This can be minimized to a certain extent by
prophylactic antibiotics.
2. Blood containing significant amounts of amniotic fluid
should not be auto transfused.
3. Blood containing wound irrigants such as Betadine;
methylmethacrylate, antibiotics not meant for parenteral
use and topical haemostatic agents should not be
salvaged.
Product:
+ The product is immediately available at body temperature.
Blood collected by ICS has a high 2, 3 DPG content so that
the haemoglobin can easily offload oxygen. The ODC is
normal or even slightly right shifted, in contrast to that of
homologous banked blood which is markedly left shifted and
normal oxygen release is not achieved for 6-12 hours post
transfusion. ICS red cells have increased osmotic resistance
with an excellent 24-hour post transfusion survival, and a
normal cell life (T Ye - 24 days). This may be because only
the younger and fitter cells survive the collection and
washing procedure.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Washed saline suspended red cells:
+ Typically 10% of the red cells are hemolyzed and lost in the washing
procedure. The level of free Hb in the salvaged blood will be between
200 and 500mg/dl although washing removes 50-70% of this. The
MCV, MCH, MCHC are normal and the majority of the cells are
morphologically normal. The hematoorit to re-infused product is
between 45 and 65%, Platelet numbers are reduced and their function
is grossly impaired, probably due to the release of B-thromboglobulin.
Washing removes all the plasma proteins, including most of the clotting
factors as well as most of the anticoagulant. Although complement
activation occurs during cell salvage the washed product is complement
tree.
Unprocessed salvaged blood:
- As this blood is not concentrated, the Hb level is between 7 and 9g/dl
and is sometimes as low as 4g/dl. The plasma Hb is normally in the
range of 60-250 mgkil but may be upto 2000 mg/dl. There is marked
increase in fibrin degradation products and D-dimers. Anticoagulant is
added to the shed blood as it is aspirated from the operative field and
this is not removed during processing. Concentrations of heparin of 3
im! and higher have been found in the re-infused blood.
COMPLICATIONS:
1) Air embolism
2) Reinfusion of hemolyzed red cells:
+ Ifthe vacuum pressure on the sucker is too high or excess turbulence
has been caused by improper aspiration technique, hemolyzed red
cells can be re-infused into the patient.
3) Coagulation disorders
4) Thrombocytopenia
5) Hypocalcaemia
7) Toxic antibiotic effects
8) Microfibrillar collagen haemostatic material
These products promote platelet adherence and aggregation leading to
local hemostasis.
6) Trauma
7) Ectopic pregnancy:
+ Thorough washing of the blood is required to prevent the
reinfusion of amniotic fluid leading to emboli and DIC.
8) Plastic surgery
9) Jehovah's witnesses
10) Serological antibodies:
+ Patients with rare and / or multiple serological antibodies
and / or other cross-match problems can be candidates for
ICs.
Contraindications:
1. Retrieval of blood from infective sites and from abdomen
with fecal soiling is to be avoided. This should be done only
as a last resort as it carries a high risk of bacteremia and
septicemia. This can be minimized to a certain extent by
prophylactic antibiotics.
2. Blood containing significant amounts of amniotic fluid
should not be auto transfused.
3. Blood containing wound irrigants such as Betadine;
methylmethacrylate, antibiotics not meant for parenteral
use and topical haemostatic agents should not be
salvaged.
Product:
+ The product is immediately available at body temperature.
Blood collected by ICS has a high 2, 3 DPG content so that
the haemoglobin can easily offload oxygen. The ODC is
normal or even slightly right shifted, in contrast to that of
homologous banked blood which is markedly left shifted and
normal oxygen release is not achieved for 6-12 hours post
transfusion. ICS red cells have increased osmotic resistance
with an excellent 24-hour post transfusion survival, and a
normal cell life (T Ye - 24 days). This may be because only
the younger and fitter cells survive the collection and
washing procedure.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Washed saline suspended red cells:
+ Typically 10% of the red cells are hemolyzed and lost in the washing
procedure. The level of free Hb in the salvaged blood will be between
200 and 500mg/dl although washing removes 50-70% of this. The
MCV, MCH, MCHC are normal and the majority of the cells are
morphologically normal. The hematoorit to re-infused product is
between 45 and 65%, Platelet numbers are reduced and their function
is grossly impaired, probably due to the release of B-thromboglobulin.
Washing removes all the plasma proteins, including most of the clotting
factors as well as most of the anticoagulant. Although complement
activation occurs during cell salvage the washed product is complement
tree.
Unprocessed salvaged blood:
- As this blood is not concentrated, the Hb level is between 7 and 9g/dl
and is sometimes as low as 4g/dl. The plasma Hb is normally in the
range of 60-250 mgkil but may be upto 2000 mg/dl. There is marked
increase in fibrin degradation products and D-dimers. Anticoagulant is
added to the shed blood as it is aspirated from the operative field and
this is not removed during processing. Concentrations of heparin of 3
im! and higher have been found in the re-infused blood.
COMPLICATIONS:
1) Air embolism
2) Reinfusion of hemolyzed red cells:
+ Ifthe vacuum pressure on the sucker is too high or excess turbulence
has been caused by improper aspiration technique, hemolyzed red
cells can be re-infused into the patient.
3) Coagulation disorders
4) Thrombocytopenia
5) Hypocalcaemia
7) Toxic antibiotic effects
8) Microfibrillar collagen haemostatic material
These products promote platelet adherence and aggregation leading to
local hemostasis.
[Autologous Blood transfusion.Continuation:
POST OPERATIVE BLOOD SALVAGE:
+ This method is mainly used after cardiothoracic surgery and
‘sometimes after joint replacements. The suction drain is
connected either to a disposable collection device or to a
cardiotomy reservoir. Anticoagulation is seldom required as
the blood is defibrinated within the mediastinum, but if the
bleeding is brisk, citrate should be added to the container.
The vacuum pressure should be between O and 40 mm Hg,
Because of the dangers of bacterial contamination the time
between the start of collection and reinfusion should be less
than 6 hours. The product contains no clotting factors,
including fibrinogen, has a hematocrit of 15-20% and
contains considerable free haemoglobin and products of clot
lysis when volumes greater than 800ml of unwashed blood
are re-infused. It has been shown that platelet function is
deranged and the patient develops a mild coagulopathy.
Others complications include prolongation of thrombin time;
upper airway oedema requiring intubation; non-cardiogenic
pulmonary oedema due to platelet and complement
activation leading to the capillary leak phenomenon.
POST TRAUMATIC SALVAGE:
+ Following chest or abdominal trauma, blood collected in
aerosal cavities is devoid of fibrinogen and hence does not
clot. This can be salvaged and auto transfused and maybe a
life saving procedure in many situation.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
ACUTE NORMOVOLAEMIC HEMODILUTION:
+ Haemodilution is defined as a dilution of all blood constituents resulting
from a limited exchange of the patient’s whole blood for cell free plasma
like fluid.
+ The phrase “isovolemic hemodilution” indicates dilution of the blood
while keeping the circulating blood volume constant. Hematocrit is the
parameter used to define the degree of haemodilution.
+ Limited or moderate preop haemodilution means an intentional
reduction of the Hct from its normal value of 0.30-0.25 immediately prior
to surgery and is used to minimize the loss of autologous red cells and
plasma components during surgery.
Contraindications to acute normovolaemic hemodilution:
1. Hematocrit less than 24%.
2. Patients with limited ability to increase cardiac output such as valvular
heart disease and intra or extra cardiac shunting.
3. Patients with respiratory insufficiency needing mechanical ventilation.
4. Patients with haemostatic defects.
Compensatory mechanisms during hemodilution:
a) Blood Rheology:
+ According to the Poiseuille’s-Hagen law, the resistance to laminar flow
of a fluid is inversely proportional to the fourth power of the radius but
directly proportional to the viscosity of the fluid and length of the tube.
+ According to the Poiseuille’s-Hagen law, the resistance to laminar flow
of a fluid is inversely proportional to the fourth power of the radius but
directly proportional to the viscosity of the fluid and length of the tube.
Q=(P1-P2) Xr /8ni
Q = flow; (Pı - Pa) = pressure drop across the tube; | = length of the
tube; r= radius of the tube ; n = viscosity of the fluid. However this
law deals only with laminar flow in a straight rigid tube.
er
POST OPERATIVE BLOOD SALVAGE:
+ This method is mainly used after cardiothoracic surgery and
‘sometimes after joint replacements. The suction drain is
connected either to a disposable collection device or to a
cardiotomy reservoir. Anticoagulation is seldom required as
the blood is defibrinated within the mediastinum, but if the
bleeding is brisk, citrate should be added to the container.
The vacuum pressure should be between O and 40 mm Hg,
Because of the dangers of bacterial contamination the time
between the start of collection and reinfusion should be less
than 6 hours. The product contains no clotting factors,
including fibrinogen, has a hematocrit of 15-20% and
contains considerable free haemoglobin and products of clot
lysis when volumes greater than 800ml of unwashed blood
are re-infused. It has been shown that platelet function is
deranged and the patient develops a mild coagulopathy.
Others complications include prolongation of thrombin time;
upper airway oedema requiring intubation; non-cardiogenic
pulmonary oedema due to platelet and complement
activation leading to the capillary leak phenomenon.
POST TRAUMATIC SALVAGE:
+ Following chest or abdominal trauma, blood collected in
aerosal cavities is devoid of fibrinogen and hence does not
clot. This can be salvaged and auto transfused and maybe a
life saving procedure in many situation.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
ACUTE NORMOVOLAEMIC HEMODILUTION:
+ Haemodilution is defined as a dilution of all blood constituents resulting
from a limited exchange of the patient’s whole blood for cell free plasma
like fluid.
+ The phrase “isovolemic hemodilution” indicates dilution of the blood
while keeping the circulating blood volume constant. Hematocrit is the
parameter used to define the degree of haemodilution.
+ Limited or moderate preop haemodilution means an intentional
reduction of the Hct from its normal value of 0.30-0.25 immediately prior
to surgery and is used to minimize the loss of autologous red cells and
plasma components during surgery.
Contraindications to acute normovolaemic hemodilution:
1. Hematocrit less than 24%.
2. Patients with limited ability to increase cardiac output such as valvular
heart disease and intra or extra cardiac shunting.
3. Patients with respiratory insufficiency needing mechanical ventilation.
4. Patients with haemostatic defects.
Compensatory mechanisms during hemodilution:
a) Blood Rheology:
+ According to the Poiseuille’s-Hagen law, the resistance to laminar flow
of a fluid is inversely proportional to the fourth power of the radius but
directly proportional to the viscosity of the fluid and length of the tube.
+ According to the Poiseuille’s-Hagen law, the resistance to laminar flow
of a fluid is inversely proportional to the fourth power of the radius but
directly proportional to the viscosity of the fluid and length of the tube.
Q=(P1-P2) Xr /8ni
Q = flow; (Pı - Pa) = pressure drop across the tube; | = length of the
tube; r= radius of the tube ; n = viscosity of the fluid. However this
law deals only with laminar flow in a straight rigid tube.
er
[Autologous Blood transfusion.Continuation:
Initial losses of energy may be considerable when flow is
constantly changing and these losses do increase with
extensive hemodilution which leads to an increased bulk flow
and an augmented kinetic energy of the blood. Turbulence is
more likely to occur if the linear flow rate is increased and
viscosity of blood is lowered; both of which are changes
initiated by hemodilution.
In hemodilution, there is a decreased red cell aggregation
and dilution of proteins like fibrinogen, hence the viscosity is
reduced
In summary, haemodilution decreases the oxygen carrying
capacity of blood and decreases the resistance to flow. An
optimal hematocrit for tissue oxygen delivery has been found
to be around 30%.
b) Utilization of oxygen:
+ Aerobic metabolism is maintained in a tissue despite a
decrease in the circulating red cell mass as a result of two
compensatory mechanisms.
1. Increased blood flow to the tissue
2. Increased oxygen extraction
c) Autonomic effects:
+ During hemodilution, there is peripheral to central
redistribution of blood mediated by alpha adrenergic
mechanism. This is basically a capacitance vessel response.
Contradictory results have been obtained regarding cardiac
autonomic function in haemodilution. Hence this technique
should be performed in caution in patients treated with
autonomic blocking agents and in patients under spinal or
epidural anesthesia.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Effect on organ systems:
1) Cardiac: The heart must increase its output as this is the main adaptive
mechanism of hemodilution compensation is achieved mainly by an
increase in coronary flow rates. Coronary vasodilatation is also important
to meet the increased demand.
ii) Cerebral: Cerebral blood flow increases during hemodilution and
normal oxygen delivery is maintained without cerebral vasodilatation.
Hyperventilation results are hypocapnia which decreases cerebral blood
flow and thus should be avoided during hemodilution.
il) Hepatic and gastrointestinal: Hepatic blood flow increases during
acute isovolumic haemodilution in proportion to the cardiac output. As the
liver receives some of its blood supply, as desaturated blood, it
compensates for this by an increased oxygen extraction. If intestinal
blood flow decreases and oxygen extraction increases, hepatic oxygen
supply via the portal vein decreases. Centrilobular hepatic necrosis has
been reported at hematocrit value below 20%
Iv) Renal: Hemodilution causes renal vasoconstriction resulting in
redistribution of blood flow to the inner cortex and a reduction in the
fraction of cardiac output to the kidney. The large renal arteriovenous
oxygen content reserve prevents impairment of tissue oxygenation.
v) Pulmonary: Hemodilution does not alter pulmonary function or
ventilation / perfusion distribution. The alveolar to arterial oxygen tension
difference decreases during hemodilution indicating better arterial
oxygenation.
vi) Pregnancy: Hemodilution should be used with caution in pregnant
patients. This is primarily due to the fact that a low matemal
hematocrit can result in inadequate oxygen content in the blood
perfusing the placenta
Methods of producing isovolaemic haemodilution:
The diluent chosen must
1. Maintain the circulatory volume
2. Not adversely affect the Oxygen Dissociation Curve
3. Not affect the rheological properties of blood,
Initial losses of energy may be considerable when flow is
constantly changing and these losses do increase with
extensive hemodilution which leads to an increased bulk flow
and an augmented kinetic energy of the blood. Turbulence is
more likely to occur if the linear flow rate is increased and
viscosity of blood is lowered; both of which are changes
initiated by hemodilution.
In hemodilution, there is a decreased red cell aggregation
and dilution of proteins like fibrinogen, hence the viscosity is
reduced
In summary, haemodilution decreases the oxygen carrying
capacity of blood and decreases the resistance to flow. An
optimal hematocrit for tissue oxygen delivery has been found
to be around 30%.
b) Utilization of oxygen:
+ Aerobic metabolism is maintained in a tissue despite a
decrease in the circulating red cell mass as a result of two
compensatory mechanisms.
1. Increased blood flow to the tissue
2. Increased oxygen extraction
c) Autonomic effects:
+ During hemodilution, there is peripheral to central
redistribution of blood mediated by alpha adrenergic
mechanism. This is basically a capacitance vessel response.
Contradictory results have been obtained regarding cardiac
autonomic function in haemodilution. Hence this technique
should be performed in caution in patients treated with
autonomic blocking agents and in patients under spinal or
epidural anesthesia.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Effect on organ systems:
1) Cardiac: The heart must increase its output as this is the main adaptive
mechanism of hemodilution compensation is achieved mainly by an
increase in coronary flow rates. Coronary vasodilatation is also important
to meet the increased demand.
ii) Cerebral: Cerebral blood flow increases during hemodilution and
normal oxygen delivery is maintained without cerebral vasodilatation.
Hyperventilation results are hypocapnia which decreases cerebral blood
flow and thus should be avoided during hemodilution.
il) Hepatic and gastrointestinal: Hepatic blood flow increases during
acute isovolumic haemodilution in proportion to the cardiac output. As the
liver receives some of its blood supply, as desaturated blood, it
compensates for this by an increased oxygen extraction. If intestinal
blood flow decreases and oxygen extraction increases, hepatic oxygen
supply via the portal vein decreases. Centrilobular hepatic necrosis has
been reported at hematocrit value below 20%
Iv) Renal: Hemodilution causes renal vasoconstriction resulting in
redistribution of blood flow to the inner cortex and a reduction in the
fraction of cardiac output to the kidney. The large renal arteriovenous
oxygen content reserve prevents impairment of tissue oxygenation.
v) Pulmonary: Hemodilution does not alter pulmonary function or
ventilation / perfusion distribution. The alveolar to arterial oxygen tension
difference decreases during hemodilution indicating better arterial
oxygenation.
vi) Pregnancy: Hemodilution should be used with caution in pregnant
patients. This is primarily due to the fact that a low matemal
hematocrit can result in inadequate oxygen content in the blood
perfusing the placenta
Methods of producing isovolaemic haemodilution:
The diluent chosen must
1. Maintain the circulatory volume
2. Not adversely affect the Oxygen Dissociation Curve
3. Not affect the rheological properties of blood,
[Autologous Blood transfusion.Continuation:
Crystalloi
+ Only a 3:1 crystalloid to blood replacement ratio is
associated with an increased cardiac output with no change
in mean arterial pressure.
Colloids:
omposition Distribution wu
d mean ial lady.
poe Lol. Wt. Interstitial cular Jo [reactions
Daltons) (vol) [oo fours)
Abumin | Albumin | 20% | 80% | >24hre | Lead
(69,000)
[Dextran 70[Polysaccharid 6 | 100% | 6-12hre Fewitreated
e (70,000) with dextran
1
Dextrand0 [Poysaccharid 6 | 100% | 23hs | Feu
e (40,000) pretreated
Fitastarch| Amplopectin| 0 | 100% | >24hrs | Few
(450,000)
Gelatin | Polypeptide | 50% | 50% | 24hrs | Few
(polygeline)| (35,000)
The amount of blood loss during isovolaemic hemodilution can
be calculated from the following equation-
Estimated blood volume x decrease in haematocrit
Blood loss initial haematocrit
+ The estimated blood volume is generally taken as 7OmlAg in
females of normal body habitus. The decrease in hematocrit
is calculated as the difference between the initial hematocrit
and the final hematocrit after isovolumic haemodilution. The
haemoglobin concentration can be substituted for the
hematocrit values in the above equation.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ The above formula is applicable when blood is lost during surgery and
is substituted with an erythrocyte free fluid after the bleeding has
‘stopped. However, in haemodilution, the blood loss is being
simultaneously replaced by a cell free infusion. Hence during the
constant exchange, the washout of the red cell decreases with time,
this is described by the equation.
Blood loss = estimated blood volume x In (Ho/H:)
Where Hois the initial hematocrit, Hy is the final hematocrit and ‘In’ is the
natural logarithm. Since this is not very practical, a reasonable accurate
‘equation is:
Estimated blood volume x decrease in haematocrit
‘Average haematocrit during haemodilution
Blood loss =
The average hematocrit during haemodilution is calculated as the
H, + 4H,
o
average of critical hematocrit and final hematocrit is 2
+ Blood can be drawn either under anesthesia or prior to induction of
anesthesia. Blood withdrawal rate must parallel the administration of
appropriate diluent volumes to assure normovolaemic and circulatory
stability. Hematocrit measurement midway throughout surgery prevents
over dilution. It is also measured at the end of haemodilution.
Crystalloi
+ Only a 3:1 crystalloid to blood replacement ratio is
associated with an increased cardiac output with no change
in mean arterial pressure.
Colloids:
omposition Distribution wu
d mean ial lady.
poe Lol. Wt. Interstitial cular Jo [reactions
Daltons) (vol) [oo fours)
Abumin | Albumin | 20% | 80% | >24hre | Lead
(69,000)
[Dextran 70[Polysaccharid 6 | 100% | 6-12hre Fewitreated
e (70,000) with dextran
1
Dextrand0 [Poysaccharid 6 | 100% | 23hs | Feu
e (40,000) pretreated
Fitastarch| Amplopectin| 0 | 100% | >24hrs | Few
(450,000)
Gelatin | Polypeptide | 50% | 50% | 24hrs | Few
(polygeline)| (35,000)
The amount of blood loss during isovolaemic hemodilution can
be calculated from the following equation-
Estimated blood volume x decrease in haematocrit
Blood loss initial haematocrit
+ The estimated blood volume is generally taken as 7OmlAg in
females of normal body habitus. The decrease in hematocrit
is calculated as the difference between the initial hematocrit
and the final hematocrit after isovolumic haemodilution. The
haemoglobin concentration can be substituted for the
hematocrit values in the above equation.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ The above formula is applicable when blood is lost during surgery and
is substituted with an erythrocyte free fluid after the bleeding has
‘stopped. However, in haemodilution, the blood loss is being
simultaneously replaced by a cell free infusion. Hence during the
constant exchange, the washout of the red cell decreases with time,
this is described by the equation.
Blood loss = estimated blood volume x In (Ho/H:)
Where Hois the initial hematocrit, Hy is the final hematocrit and ‘In’ is the
natural logarithm. Since this is not very practical, a reasonable accurate
‘equation is:
Estimated blood volume x decrease in haematocrit
‘Average haematocrit during haemodilution
Blood loss =
The average hematocrit during haemodilution is calculated as the
H, + 4H,
o
average of critical hematocrit and final hematocrit is 2
+ Blood can be drawn either under anesthesia or prior to induction of
anesthesia. Blood withdrawal rate must parallel the administration of
appropriate diluent volumes to assure normovolaemic and circulatory
stability. Hematocrit measurement midway throughout surgery prevents
over dilution. It is also measured at the end of haemodilution.
[Autologous Blood transfusion.Continuation:
Advantages of autologous transfusion:
+ Eliminates the risk of transfusion reaction
+ Eliminates the risk of disease transmission.
+ Eliminates the risk of alloimmunization to red cells, white
cells, platelets or plasma proteins.
+ Eliminates the risk of transfusion transmitted graft VS host
disease.
+ Allows safe transfusions in patients with multiple
alloantibodies or with rare blood groups.
+ Pre-deposit donation “stimulates” erythropoeisis prior to
surgery.
+ Hemodilution improves tissue oxygen perfusion by lowering
the blood viscosity.
+ Provides blood cover for some Jehovah's witnesses.
+ Provides readily available blood in cases of major
hemorthages.
+ Reduces the demand on homologous blood supply in remote
areas or developing countries,
+ Gives patients the psychological benefit of activity
participating in their treatment.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Disadvantage of autologous transfusion:
+ Complex logistics for collection; storage and transfusion of the correct
unit to the appropriate patient.
+ Only suitable for certain operative procedures.
+ Tendency to over transtuse.
+ Ifthe surgical procedure is delayed; the blood may become outdated,
+ Bacterial contamination
+ Patient is made grossly anemic by either too frequent pre-deposit
donation or over hemodilution.
+ Coagulation defects
+ Incorrect techniques can cause red cell hemolysis.
+ Equipment for intraoperative blood salvage is expensive and requires
trained staff.
+ Tends to give a misguided impression that normal homologous
donations are unsafe.
Precautions:
+ Agents such as atropine and pancuronium which cause tachycardia are
best avoided. Monitoring should include ECG: urine output;
temperature, central venous pressure and preferably invasive arterial
pressure. Ventilation should be adjusted to prevent acidosis or a left
ward shift of the ODC caused by alkalosis resulting from
hyperventilation.
+ Blood is drawn into standard bags containing acid citrate dextrose
(ACD) solution and stored at room temperature, Reinfusion of the
patient's blood should ideally be undertaken when operative bleeding
has ceased. Units of blood which were drawn last should be transfused
first. A filter should not be used in the administration set.
70
Advantages of autologous transfusion:
+ Eliminates the risk of transfusion reaction
+ Eliminates the risk of disease transmission.
+ Eliminates the risk of alloimmunization to red cells, white
cells, platelets or plasma proteins.
+ Eliminates the risk of transfusion transmitted graft VS host
disease.
+ Allows safe transfusions in patients with multiple
alloantibodies or with rare blood groups.
+ Pre-deposit donation “stimulates” erythropoeisis prior to
surgery.
+ Hemodilution improves tissue oxygen perfusion by lowering
the blood viscosity.
+ Provides blood cover for some Jehovah's witnesses.
+ Provides readily available blood in cases of major
hemorthages.
+ Reduces the demand on homologous blood supply in remote
areas or developing countries,
+ Gives patients the psychological benefit of activity
participating in their treatment.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Disadvantage of autologous transfusion:
+ Complex logistics for collection; storage and transfusion of the correct
unit to the appropriate patient.
+ Only suitable for certain operative procedures.
+ Tendency to over transtuse.
+ Ifthe surgical procedure is delayed; the blood may become outdated,
+ Bacterial contamination
+ Patient is made grossly anemic by either too frequent pre-deposit
donation or over hemodilution.
+ Coagulation defects
+ Incorrect techniques can cause red cell hemolysis.
+ Equipment for intraoperative blood salvage is expensive and requires
trained staff.
+ Tends to give a misguided impression that normal homologous
donations are unsafe.
Precautions:
+ Agents such as atropine and pancuronium which cause tachycardia are
best avoided. Monitoring should include ECG: urine output;
temperature, central venous pressure and preferably invasive arterial
pressure. Ventilation should be adjusted to prevent acidosis or a left
ward shift of the ODC caused by alkalosis resulting from
hyperventilation.
+ Blood is drawn into standard bags containing acid citrate dextrose
(ACD) solution and stored at room temperature, Reinfusion of the
patient's blood should ideally be undertaken when operative bleeding
has ceased. Units of blood which were drawn last should be transfused
first. A filter should not be used in the administration set.
70
25. Massive Blood Transfusion.
Definition:
+ Massive blood transfusion may be defined either as the
acute administration of more than 1.5 times the patients total
blood volume by homologous blood in less than 24 hours.
+ Also defined as transfusion of one pint of blood with in 5
minutes; or transfusion of 5 units within 1 hr or transfusion of
10 units within Ghrs, or transfusion of >10% of blood volume
within 10 minutes.
Precautions:
+ Atleast 2 large gauge venous cannula (12 gauge) should be
‘secured; solely for the purpose of blood transfusion.
if peripheral venous access is difficult, cannula may be
inserted into a large, central vein such as the subclavian,
intemal jugular or femoral vein. A venous cut down may also
be altematively performed in the saphenous vein at the
ankle.
In addition an arterial catheter and triple lumen central
venous catheter may be useful in allowing rapid blood
sampling and direct measurement of arterial and central
venous pressures respectively. The triple lumen catheter
also provides access for intermittent bolus administration of
drugs or drug infusions.
Altematively (or in addition) a sheath introducer (8 French
gauge) may be inserted into the central vein; providing a
large cannula for transfusion and means whereby a
pulmonary artery catheter can be inserted, when indicated.
Unless contraindicated by pelvic or urethral injury; a urethral
catheter should be passed and urine output measured
(intermittently) hourly.
+ Central and peripheral temperature should be recorded.
+ Pulse oximeter — for heart rate and oxygen saturation
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ Needles and sharp objects should be handled and disposed of carefully
to avoid needle stick injury.
+ Wearing of gloves is recommended, to prevent contamination of hands
with spilled blood.
+ Use of 3-way taps with or without extension tubing reduces the need to
use needles for drug administration or blood sampling.
Pressure bags, blood warming and rapid infusion devices:
+ Major haemorrhage may require the transfusion of blood at fast flow
rates (upto 500ml/min) and at temperatures greater than 35 °C.
+ This can be achieved by using a constant pressure infusion device
combined with an efficient blood warmer and a purpose designed
double length blood warming coil.
+ Efficient counter current aluminum heat exchanges have been
investigated under conditions of high flow and have been found to be
effective.
+ Priming or flushing blood through the system with fluids containing
calcium (such as compound sodium lactate and haemacel) should be
avoided, as this may result in blood clot formation in the tubing. This is
due to the reversal of the anticoagulant effect of citrate by calcium ions.
+ The hematinics rapid infuser device has a 3 litre reservoir into which
cell saved or banked blood and FFP can be stored, warmed and
infused at rates of upto 21/min
+ If such equipment for rapid transfusion is not available the speed of
transfusion can be increased by simple maneuvers for e.g. increasing
height of fluid above the patient or using intermittent manual
compression of the lower chamber of the giving set when full of fluid
Altematively using a large syringe and a 3-way tap in line; fluid can be
drawn rapidly into the syringe from the giving set before being
administered to the patient through the 3-way tap.
+ A manually operated Martin's rotatory pump may be used (not available
now)
n
Definition:
+ Massive blood transfusion may be defined either as the
acute administration of more than 1.5 times the patients total
blood volume by homologous blood in less than 24 hours.
+ Also defined as transfusion of one pint of blood with in 5
minutes; or transfusion of 5 units within 1 hr or transfusion of
10 units within Ghrs, or transfusion of >10% of blood volume
within 10 minutes.
Precautions:
+ Atleast 2 large gauge venous cannula (12 gauge) should be
‘secured; solely for the purpose of blood transfusion.
if peripheral venous access is difficult, cannula may be
inserted into a large, central vein such as the subclavian,
intemal jugular or femoral vein. A venous cut down may also
be altematively performed in the saphenous vein at the
ankle.
In addition an arterial catheter and triple lumen central
venous catheter may be useful in allowing rapid blood
sampling and direct measurement of arterial and central
venous pressures respectively. The triple lumen catheter
also provides access for intermittent bolus administration of
drugs or drug infusions.
Altematively (or in addition) a sheath introducer (8 French
gauge) may be inserted into the central vein; providing a
large cannula for transfusion and means whereby a
pulmonary artery catheter can be inserted, when indicated.
Unless contraindicated by pelvic or urethral injury; a urethral
catheter should be passed and urine output measured
(intermittently) hourly.
+ Central and peripheral temperature should be recorded.
+ Pulse oximeter — for heart rate and oxygen saturation
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ Needles and sharp objects should be handled and disposed of carefully
to avoid needle stick injury.
+ Wearing of gloves is recommended, to prevent contamination of hands
with spilled blood.
+ Use of 3-way taps with or without extension tubing reduces the need to
use needles for drug administration or blood sampling.
Pressure bags, blood warming and rapid infusion devices:
+ Major haemorrhage may require the transfusion of blood at fast flow
rates (upto 500ml/min) and at temperatures greater than 35 °C.
+ This can be achieved by using a constant pressure infusion device
combined with an efficient blood warmer and a purpose designed
double length blood warming coil.
+ Efficient counter current aluminum heat exchanges have been
investigated under conditions of high flow and have been found to be
effective.
+ Priming or flushing blood through the system with fluids containing
calcium (such as compound sodium lactate and haemacel) should be
avoided, as this may result in blood clot formation in the tubing. This is
due to the reversal of the anticoagulant effect of citrate by calcium ions.
+ The hematinics rapid infuser device has a 3 litre reservoir into which
cell saved or banked blood and FFP can be stored, warmed and
infused at rates of upto 21/min
+ If such equipment for rapid transfusion is not available the speed of
transfusion can be increased by simple maneuvers for e.g. increasing
height of fluid above the patient or using intermittent manual
compression of the lower chamber of the giving set when full of fluid
Altematively using a large syringe and a 3-way tap in line; fluid can be
drawn rapidly into the syringe from the giving set before being
administered to the patient through the 3-way tap.
+ A manually operated Martin's rotatory pump may be used (not available
now)
n
[Massive Blood Transfusion.Continuation:
‘Complications:
1) Coagulation changes:
+ In situations other than those of liver transplantation and in
patients with a pre-existing coagulopathy; it is unusual for a
Significant reduction of plasma coagulation factors to occur
solely as a result of massive transfusion of stored whole
blood
+ Stored whole blood contains adequate amounts of
coagulation factors |, Il, VII, IX, X, XI and XII. Concentrations
of factors V and VII are reduced in stored blood.
Causes of coagulopathy after massive blood transfusion;
1. Preexisting defects caused by the underlying disease or
drugs used.
2. Dilution by replacement therapy.
3. Artificial plasma expanders e.g. dextran and hydroxyethyl
starch.
Stress
Tissue injury
Shock
. Bacteremia
+ In patients with severe liver disease; the pre-existing
coagulopathy consists of a decrease in platelet count and all
coagulation factors except factors | and V (because of a
decrease in synthetic ability of liver). This leads to increased
prothrombin time (PT) and APTT.
‘Treatment:
+ Administration of platelets and FFP
+ Dose: 1 Unit of FFP for every 10 kg
+ 2 unit FFP for each 10unit of blood transfused
+ 6 unit Platelet concentration for every 20u of blood
transfused
+ Basic screening tests for bleeding after operation-- Platelet
count; prothrombin time; APTT, plasma fibrinogen
concentration and fibrinogen degradation products when
indicated.
sons
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
2) Citrate toxicity: 1 in ionized calcium
+ Each unit of blood contains approx. 3gms of citrate as an anticoagulant.
In normal circumstances the liver metabolizes this rapidly. Liver
metabolism must be impaired before citrate metabolism becomes
overwhelmed.
Citrate binds to ionized calcium fraction in blood and causes a
decrease in myocardial function, hypotension, small pulse pressure and
increased diastolic and central venous pressures.
Transient changes in ionized calcium concentrations causes little
hemodynamic disturbance and the routine use of calcium with blood
transfusion is not recommended unless hepatic function is
compromised. This may be caused by a low cardiac output;
hypothermia’ liver dés; or liver transplantation and in these situations,
chances of developing a decreased calcium concentration and citrate
toxicity is increased.
Calcium also plays a role in both extrinsic and intrinsic coagulation
pathways. A bleeding diathesis associated with hypocalcaemia is
uncommon as cardiac arrest is said to occur before the plasma
concentration decreases to a value that affects coagulation.
‘Treatment:
+ The adverse effects of hypocalcaemia can be treated by administration
of calcium chloride if the patients become hypotensive and is not
hypovolemia; or on the basis of a measured decrease in plasma
concentration of ionized calcium.
+ Calcium gluconate is less effective than calcium chloride because it
must be metabolized to be effective.
72
‘Complications:
1) Coagulation changes:
+ In situations other than those of liver transplantation and in
patients with a pre-existing coagulopathy; it is unusual for a
Significant reduction of plasma coagulation factors to occur
solely as a result of massive transfusion of stored whole
blood
+ Stored whole blood contains adequate amounts of
coagulation factors |, Il, VII, IX, X, XI and XII. Concentrations
of factors V and VII are reduced in stored blood.
Causes of coagulopathy after massive blood transfusion;
1. Preexisting defects caused by the underlying disease or
drugs used.
2. Dilution by replacement therapy.
3. Artificial plasma expanders e.g. dextran and hydroxyethyl
starch.
Stress
Tissue injury
Shock
. Bacteremia
+ In patients with severe liver disease; the pre-existing
coagulopathy consists of a decrease in platelet count and all
coagulation factors except factors | and V (because of a
decrease in synthetic ability of liver). This leads to increased
prothrombin time (PT) and APTT.
‘Treatment:
+ Administration of platelets and FFP
+ Dose: 1 Unit of FFP for every 10 kg
+ 2 unit FFP for each 10unit of blood transfused
+ 6 unit Platelet concentration for every 20u of blood
transfused
+ Basic screening tests for bleeding after operation-- Platelet
count; prothrombin time; APTT, plasma fibrinogen
concentration and fibrinogen degradation products when
indicated.
sons
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
2) Citrate toxicity: 1 in ionized calcium
+ Each unit of blood contains approx. 3gms of citrate as an anticoagulant.
In normal circumstances the liver metabolizes this rapidly. Liver
metabolism must be impaired before citrate metabolism becomes
overwhelmed.
Citrate binds to ionized calcium fraction in blood and causes a
decrease in myocardial function, hypotension, small pulse pressure and
increased diastolic and central venous pressures.
Transient changes in ionized calcium concentrations causes little
hemodynamic disturbance and the routine use of calcium with blood
transfusion is not recommended unless hepatic function is
compromised. This may be caused by a low cardiac output;
hypothermia’ liver dés; or liver transplantation and in these situations,
chances of developing a decreased calcium concentration and citrate
toxicity is increased.
Calcium also plays a role in both extrinsic and intrinsic coagulation
pathways. A bleeding diathesis associated with hypocalcaemia is
uncommon as cardiac arrest is said to occur before the plasma
concentration decreases to a value that affects coagulation.
‘Treatment:
+ The adverse effects of hypocalcaemia can be treated by administration
of calcium chloride if the patients become hypotensive and is not
hypovolemia; or on the basis of a measured decrease in plasma
concentration of ionized calcium.
+ Calcium gluconate is less effective than calcium chloride because it
must be metabolized to be effective.
72
[Massive Blood Transfusion.Continuation:
3) Potassium:
K+ in stored blood increases to almost 30mmolA after 3
weeks of storage. After transfusion, viable RBC establishes
their ionic pumping mechanism and intracellular reuptake of
K+ occurs.
+ Transient hyperkalemia has been observed during massive
blood transfusion and correlates strongly with the rate of
transfusion. Therefore ECG monitoring is advisable during
massive blood transfusions.
4) Acid-base disturbances:
+ 3 Week old stored blood (citrated) contains an acid load of
upto 30-40 mmol and this originates mainly from the citric
acid of the anticoagulant and lactic acid generated by red
cells during storage.
+ Citrate is metabolized to bicarbonate and may produce a
profound metabolic alkalosis after transfusion because of this
itis not necessary to correct minor degrees of metabolic
acidosis.
+ Shocked patients more likely to develop metabolic acidosis.
5) Hypothermia:
+ The problems attributable to hypothermia include reduction
in citrate and lactate metabolism (thereby increasing the
probability that patient will develop hypocalcaemia and
metabolic acidosis during transfusion), an increase in the
affinity of Hb for O2; impairment of red cell deformity; platelet
dysfunction and bleeding and an increased tendency to
cardiac arrhythmias.
+ Therefore core temperature measurement is important
during massive blood transfusion and can be measured with
a temperature probe at the midpoint of the oesophagus.
+ Body temperature may decrease because of administration
of large volumes of cold fluids and blood (which is stored at
490) or because of loss of radiant heat and latent heat of
‘evaporation of body fluids from the open abdominal or
thoracic cavity or skin (especially in bum patients).
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
‘Treatment:
|. Placing patient on a heated “ripple” mattress
IL Warming IV fluids
III. Covering patient with thermally insulating drapes.
IV. In small children, an overhead infra-red heater minimizes heat loss
from radiation.
V. The ambient temperature of the theatre may be increased.
6) Pulmonary dysfunction: TRALI
+ Pulmonary dysfunction after transfusion is caused or exacerbated by
the formation and subsequent administration micro-aggregates formed
in stored blood.
+ They are composed largely of degenerating platelets; granulocytes;
denatured proteins; fibrin strands and other debris and their rate of
formation and size (10-200um in diameter) vary according to the
different types of storage solutions.
+ Blood filters have been designed to remove micro-aggregates and are
of 2 types.
+ Depth filters: which remove particles by impaction and adsorption
+ Screen filters: which operate on a direct interception principle and have
an absolute poor size rating of 40um (the standard blood administration
set has a pore size of 170um).
BLOOD TRANSFUSION REACTIONS
+ Major life threatening complications following blood transfusion are rare
and human error remains an important etiological factors in many.
+ Complications that can accompany administration of blood / blood
components include
|. Transfusion reactions
Il. Metabolic abnormalities — H*, K*, citrate
lil, Transmission of diseases — hepatitis, HIV, viral, bacterial protozoal
IV. Microaggregate infusion — post transfusion pulmonary dysfunction.
73
3) Potassium:
K+ in stored blood increases to almost 30mmolA after 3
weeks of storage. After transfusion, viable RBC establishes
their ionic pumping mechanism and intracellular reuptake of
K+ occurs.
+ Transient hyperkalemia has been observed during massive
blood transfusion and correlates strongly with the rate of
transfusion. Therefore ECG monitoring is advisable during
massive blood transfusions.
4) Acid-base disturbances:
+ 3 Week old stored blood (citrated) contains an acid load of
upto 30-40 mmol and this originates mainly from the citric
acid of the anticoagulant and lactic acid generated by red
cells during storage.
+ Citrate is metabolized to bicarbonate and may produce a
profound metabolic alkalosis after transfusion because of this
itis not necessary to correct minor degrees of metabolic
acidosis.
+ Shocked patients more likely to develop metabolic acidosis.
5) Hypothermia:
+ The problems attributable to hypothermia include reduction
in citrate and lactate metabolism (thereby increasing the
probability that patient will develop hypocalcaemia and
metabolic acidosis during transfusion), an increase in the
affinity of Hb for O2; impairment of red cell deformity; platelet
dysfunction and bleeding and an increased tendency to
cardiac arrhythmias.
+ Therefore core temperature measurement is important
during massive blood transfusion and can be measured with
a temperature probe at the midpoint of the oesophagus.
+ Body temperature may decrease because of administration
of large volumes of cold fluids and blood (which is stored at
490) or because of loss of radiant heat and latent heat of
‘evaporation of body fluids from the open abdominal or
thoracic cavity or skin (especially in bum patients).
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
‘Treatment:
|. Placing patient on a heated “ripple” mattress
IL Warming IV fluids
III. Covering patient with thermally insulating drapes.
IV. In small children, an overhead infra-red heater minimizes heat loss
from radiation.
V. The ambient temperature of the theatre may be increased.
6) Pulmonary dysfunction: TRALI
+ Pulmonary dysfunction after transfusion is caused or exacerbated by
the formation and subsequent administration micro-aggregates formed
in stored blood.
+ They are composed largely of degenerating platelets; granulocytes;
denatured proteins; fibrin strands and other debris and their rate of
formation and size (10-200um in diameter) vary according to the
different types of storage solutions.
+ Blood filters have been designed to remove micro-aggregates and are
of 2 types.
+ Depth filters: which remove particles by impaction and adsorption
+ Screen filters: which operate on a direct interception principle and have
an absolute poor size rating of 40um (the standard blood administration
set has a pore size of 170um).
BLOOD TRANSFUSION REACTIONS
+ Major life threatening complications following blood transfusion are rare
and human error remains an important etiological factors in many.
+ Complications that can accompany administration of blood / blood
components include
|. Transfusion reactions
Il. Metabolic abnormalities — H*, K*, citrate
lil, Transmission of diseases — hepatitis, HIV, viral, bacterial protozoal
IV. Microaggregate infusion — post transfusion pulmonary dysfunction.
73
[Massive Blood Transfusion.Continuation:
|, Transfusion reactions:
Immediate reactions:
1. Febrile reactions (due to ab. to donor, leukocyte Ag)
2. Hemolytic (red cell incompatibility
3, Anaphylaxis (Ab to IgA of donor)
4, Urticaria (allergic - due to Ab to plasma proteins)
5. Non-cardiogenic pulmonary oedema (donor antibodies
to pt. leucocytes)
6. Fever with shock (bacterial)
7. CCF (fluid overload)
Delayed reactions:
1. Hemolysis
2 GVHD
3, Purpura
4. Alloimmunization
1) Allergie reactions:
+ Can occur in 3% of correctly typed and cross matched blood
transfusion. Incompatible plasma proteins (Haptogens) are
the probable cause, Manifestations include pruritis, erythema
and urticaria often accompanied by increase in body
temperature and eosinophilia. Rarely laryngospasm and
bronchospasm are also present. Under anesthesia the first
manifestation of allergic reactions due to blood transfusion
may be the appearance of erythema along the pathway of
the vein receiving the blood plus urticaria particularly on the
chest, neck, face,
- Serious anaphylactic reactions are most likely to occur in
patients who lack IgA. These patients have an anti IgA and
can develop severe allergic reactions when they are
administered serum containing IgA such patients should
receive transfusion only from IgA deficient donors.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
2) Febrile reactions:
+ Are the most common non hemolytic reaction. This is due to interaction
between Abs and Ag's present in leucocytes and or platelets of the
donor. Fever results from the release of pyrogenic substances from
injured celts,
- Body temperature may increase within 4 hrs after starting the
transfusion. Headache, nausea, vomiting and chest or back pain may
accompany the elevation of body temperature. Treatment of mild febrile
reactions is by slowing the rate of infusion of blood and by
administration of paracetamol. Pethidine 25mg iv to adults, is useful for
the treatment of shivering which may accompany the reactions —
severe febrile reactions may require discontinuation of the blood
infusion.
3) Hemolytic reactions:
Hemolytic reactions are almost mainly due to ABO incompatibility.
Although rare, they are a major cause of transfusion associated mortality.
+ The quantity of antibody in acute hemolytic reactions appear to
determine the resultant morbidity and mortality.
+ Group O recipients have both anti A and B in their plasma. If group O
recipient, receive type A, B or AB blood, the biological consequences of
this incompatibility to the patient are greater than after a small volume
of donor plasma containing antibodies directed against the recipient
cellsis transfused (Le. group O to a recipient of group A, B or AB).
+ The Ag-Ab interaction activates the complement cascade and this
results in lysis of donor cells — intravascular hemolysis.
+ Complement activation results in release of complement fragments (C3,
C5) and histamine which are potent vasodilating compounds and
enhance capillary permeability. This leads to hypotension.
+ DIC is initiated by material released from hemolyzed erythrocytes,
leading to thrombocytopenia and increased circulatory concentrations
of fibrin degradation products.
+ Elevation of unconjugated fractions of bilirubin in plasma are maximal
3-6 hrs after the onset of hemolytic reactions.
+ Renal damage resulting in acute renal failure is a consequence of
multiple factors including:
74
|, Transfusion reactions:
Immediate reactions:
1. Febrile reactions (due to ab. to donor, leukocyte Ag)
2. Hemolytic (red cell incompatibility
3, Anaphylaxis (Ab to IgA of donor)
4, Urticaria (allergic - due to Ab to plasma proteins)
5. Non-cardiogenic pulmonary oedema (donor antibodies
to pt. leucocytes)
6. Fever with shock (bacterial)
7. CCF (fluid overload)
Delayed reactions:
1. Hemolysis
2 GVHD
3, Purpura
4. Alloimmunization
1) Allergie reactions:
+ Can occur in 3% of correctly typed and cross matched blood
transfusion. Incompatible plasma proteins (Haptogens) are
the probable cause, Manifestations include pruritis, erythema
and urticaria often accompanied by increase in body
temperature and eosinophilia. Rarely laryngospasm and
bronchospasm are also present. Under anesthesia the first
manifestation of allergic reactions due to blood transfusion
may be the appearance of erythema along the pathway of
the vein receiving the blood plus urticaria particularly on the
chest, neck, face,
- Serious anaphylactic reactions are most likely to occur in
patients who lack IgA. These patients have an anti IgA and
can develop severe allergic reactions when they are
administered serum containing IgA such patients should
receive transfusion only from IgA deficient donors.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
2) Febrile reactions:
+ Are the most common non hemolytic reaction. This is due to interaction
between Abs and Ag's present in leucocytes and or platelets of the
donor. Fever results from the release of pyrogenic substances from
injured celts,
- Body temperature may increase within 4 hrs after starting the
transfusion. Headache, nausea, vomiting and chest or back pain may
accompany the elevation of body temperature. Treatment of mild febrile
reactions is by slowing the rate of infusion of blood and by
administration of paracetamol. Pethidine 25mg iv to adults, is useful for
the treatment of shivering which may accompany the reactions —
severe febrile reactions may require discontinuation of the blood
infusion.
3) Hemolytic reactions:
Hemolytic reactions are almost mainly due to ABO incompatibility.
Although rare, they are a major cause of transfusion associated mortality.
+ The quantity of antibody in acute hemolytic reactions appear to
determine the resultant morbidity and mortality.
+ Group O recipients have both anti A and B in their plasma. If group O
recipient, receive type A, B or AB blood, the biological consequences of
this incompatibility to the patient are greater than after a small volume
of donor plasma containing antibodies directed against the recipient
cellsis transfused (Le. group O to a recipient of group A, B or AB).
+ The Ag-Ab interaction activates the complement cascade and this
results in lysis of donor cells — intravascular hemolysis.
+ Complement activation results in release of complement fragments (C3,
C5) and histamine which are potent vasodilating compounds and
enhance capillary permeability. This leads to hypotension.
+ DIC is initiated by material released from hemolyzed erythrocytes,
leading to thrombocytopenia and increased circulatory concentrations
of fibrin degradation products.
+ Elevation of unconjugated fractions of bilirubin in plasma are maximal
3-6 hrs after the onset of hemolytic reactions.
+ Renal damage resulting in acute renal failure is a consequence of
multiple factors including:
74
[Massive Blood Transfusion.Continuation:
Glomerular deposition of fibrin
Reduced renal blood flow, due to histamine induced
vasomotor changes.
Precipitation of stromal and lipid contents and erythrocytes
in distal renal tubules.
Free Hb does not directly damage the kidneys but can
contribute to renal failure if it is precipitated in the renal
tubules and blocks the tubules.
5. Acute tubular necrosis — results from Ag-Ab reactions >
release of tonic substances from RBC > vasoconstriction.
In the anaesthetized patient, the immediate signs and
symptoms of hemolytic reactions are masked. Hypotension
and abnormal bleeding may be the only finding
8 & No
‘Schematic representation of what happens to hemolyzed
erythrocytes as a result of the administration of incompatible
blood:
Ll
Free haemoglobin
Z ON
Haemoglobin-haptoglobin Kidney
complex
(100m9%)
{
Reticulo-endothelial
system
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ As little as 50m! of incompatible blood may exceed the binding capacity
of haemoglobin, which is a protein that can bind about 100mg of
hemoglobin per 100m! of plasma. When hemoglobin not exceeding this
amount is injected or liberated into the blood stream, the Hb circulates
as a complex with the haptoglobin, which is cleared by the
reticuloendothelial system. A sample of plasma that contains 2mg/dl of
haemoglobin is faintly pink or light brown. When the level of Hb reaches
100mgidl, then the plasma is red. When the plasma hemoglobin
teaches 150mg/dl, hemoglobinuria occurs. In general, the quantity of
free haemoglobin in the plasma is correlated with the volume of
incompatible blood transfused
Lab tests that should be performed if hemolytic transfusion reactions are
suspected include
+ Serum haptoglobin
+ Plasma and urine haemoglobin
- Bilirubin
+ Direct antiglobulin-confirms the presence of hemolytic transfusion
reaction because it shows that there is antibody attached to transfused
donor red blood cells.
h) Signs and symptoms of hemolytic transfusion reaction:
+ Fever and chills
+ Chest pain
+ Hypotension
+ Nausea
+ Flushing
+ Dyspnoea
+ Hemoglobinuria
75
Glomerular deposition of fibrin
Reduced renal blood flow, due to histamine induced
vasomotor changes.
Precipitation of stromal and lipid contents and erythrocytes
in distal renal tubules.
Free Hb does not directly damage the kidneys but can
contribute to renal failure if it is precipitated in the renal
tubules and blocks the tubules.
5. Acute tubular necrosis — results from Ag-Ab reactions >
release of tonic substances from RBC > vasoconstriction.
In the anaesthetized patient, the immediate signs and
symptoms of hemolytic reactions are masked. Hypotension
and abnormal bleeding may be the only finding
8 & No
‘Schematic representation of what happens to hemolyzed
erythrocytes as a result of the administration of incompatible
blood:
Ll
Free haemoglobin
Z ON
Haemoglobin-haptoglobin Kidney
complex
(100m9%)
{
Reticulo-endothelial
system
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ As little as 50m! of incompatible blood may exceed the binding capacity
of haemoglobin, which is a protein that can bind about 100mg of
hemoglobin per 100m! of plasma. When hemoglobin not exceeding this
amount is injected or liberated into the blood stream, the Hb circulates
as a complex with the haptoglobin, which is cleared by the
reticuloendothelial system. A sample of plasma that contains 2mg/dl of
haemoglobin is faintly pink or light brown. When the level of Hb reaches
100mgidl, then the plasma is red. When the plasma hemoglobin
teaches 150mg/dl, hemoglobinuria occurs. In general, the quantity of
free haemoglobin in the plasma is correlated with the volume of
incompatible blood transfused
Lab tests that should be performed if hemolytic transfusion reactions are
suspected include
+ Serum haptoglobin
+ Plasma and urine haemoglobin
- Bilirubin
+ Direct antiglobulin-confirms the presence of hemolytic transfusion
reaction because it shows that there is antibody attached to transfused
donor red blood cells.
h) Signs and symptoms of hemolytic transfusion reaction:
+ Fever and chills
+ Chest pain
+ Hypotension
+ Nausea
+ Flushing
+ Dyspnoea
+ Hemoglobinuria
75
[Massive Blood Transfusion.Continuation:
The treatment of a hemolytic transfusion reaction:
+ Stop transfusion
+ Maintain the urine output at a minimum of 75-100ml/hr by the
following methods:
1. Generously administer fluids intravenously and possibly
Mannitol 12.5 to 50gm given over a to 15 min period
2. If intravenously administered fluids and mannitol are
ineffective then administer furosemide 20-40 mg/hr.
3. Alkalinize the urine, because bicarbonate is
preferentially excreted in the urine; only 40-70mEq/70kg
of body wt. Sodium bicarbonate is usually required to
raise the urine pH to 8. Where upon repeat urine pH
determinations indicate the need for additional
bicarbonate.
4, Assay urine and plasma Hb concentrations.
5. Determine platelet count; partial thromboplastin time
and serum fibrinogen level
6. Return unused blood to blood bank for re-cross match.
7. Send patient blood and urine sample to blood bank for
examination.
8. Prevent hypotension to ensure adequate renal blood
flow.
9. Maintain IV line, O2 therapy; resuscitative measures.
10. Antihistamine — diphenhydramine 0.5-1mg/kg IV.
11. Steroid - hydrocortisone - 2-4mg/kg IV.
12. Antibiotics.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Il. Metabolic abnormalities:
Metabolic abnormalities produced by administration of blood are related
to changes that occur during storage.
+ Hydrogen ions: 30mmol/L after 3 weeks
+ Hydrogen ion content of stored blood is initially increased by the
addition of ACD (pH. 5) or CPD (pH 5.5) causing the pH of freshly
drawn blood to decrease to 7-7.1. Continued metabolic function of
erythrocytes results in additional production of hydrogen ions.
+ Furthermore CO2 partial pressure increases between 150mmHg and
200mmHg since this gas cannot diffuse through glass or plastic
containers.
+ Despite these changes, metabolic acidosis is not a common,
occurrence, even with the rapid infusion of large volumes of stored
blood
+ Metabolic alkalosis, rather than metabolic acidosis, is a frequent
accompaniment of massive blood transfusion. This alkalosis is
preserved to be partly due to metabolism of infused citrate to
bicarbonate, which could further be exaggerated by administration of
lactated ringer's solution.
Potassium:
+ Potassium content of ACD blood reaches about 14mEg/ by 7 days of
storage and increases further to 21mEg/ to 24 mEgf after 21 days,
Potassium levels of blood stored in CPD are about 20% lower. Stil,
nevertheless, massive transfusions of stored blood rarely increase
plasma concentration of potassium.
+ The metabolic alkalosis produced by massive transfusions of whole
blood favor transfer of K+ from extracellular fluid into intracellular
spaces, offsetting any tendency toward hyperkalemia, However, in
patients with impaired or absent renal function, transfusion of blood
could produce hyperkalemia,
76
The treatment of a hemolytic transfusion reaction:
+ Stop transfusion
+ Maintain the urine output at a minimum of 75-100ml/hr by the
following methods:
1. Generously administer fluids intravenously and possibly
Mannitol 12.5 to 50gm given over a to 15 min period
2. If intravenously administered fluids and mannitol are
ineffective then administer furosemide 20-40 mg/hr.
3. Alkalinize the urine, because bicarbonate is
preferentially excreted in the urine; only 40-70mEq/70kg
of body wt. Sodium bicarbonate is usually required to
raise the urine pH to 8. Where upon repeat urine pH
determinations indicate the need for additional
bicarbonate.
4, Assay urine and plasma Hb concentrations.
5. Determine platelet count; partial thromboplastin time
and serum fibrinogen level
6. Return unused blood to blood bank for re-cross match.
7. Send patient blood and urine sample to blood bank for
examination.
8. Prevent hypotension to ensure adequate renal blood
flow.
9. Maintain IV line, O2 therapy; resuscitative measures.
10. Antihistamine — diphenhydramine 0.5-1mg/kg IV.
11. Steroid - hydrocortisone - 2-4mg/kg IV.
12. Antibiotics.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Il. Metabolic abnormalities:
Metabolic abnormalities produced by administration of blood are related
to changes that occur during storage.
+ Hydrogen ions: 30mmol/L after 3 weeks
+ Hydrogen ion content of stored blood is initially increased by the
addition of ACD (pH. 5) or CPD (pH 5.5) causing the pH of freshly
drawn blood to decrease to 7-7.1. Continued metabolic function of
erythrocytes results in additional production of hydrogen ions.
+ Furthermore CO2 partial pressure increases between 150mmHg and
200mmHg since this gas cannot diffuse through glass or plastic
containers.
+ Despite these changes, metabolic acidosis is not a common,
occurrence, even with the rapid infusion of large volumes of stored
blood
+ Metabolic alkalosis, rather than metabolic acidosis, is a frequent
accompaniment of massive blood transfusion. This alkalosis is
preserved to be partly due to metabolism of infused citrate to
bicarbonate, which could further be exaggerated by administration of
lactated ringer's solution.
Potassium:
+ Potassium content of ACD blood reaches about 14mEg/ by 7 days of
storage and increases further to 21mEg/ to 24 mEgf after 21 days,
Potassium levels of blood stored in CPD are about 20% lower. Stil,
nevertheless, massive transfusions of stored blood rarely increase
plasma concentration of potassium.
+ The metabolic alkalosis produced by massive transfusions of whole
blood favor transfer of K+ from extracellular fluid into intracellular
spaces, offsetting any tendency toward hyperkalemia, However, in
patients with impaired or absent renal function, transfusion of blood
could produce hyperkalemia,
76
[Massive Blood Transfusion.Continuation:
Decreased 2, 3 diphosphoglycerate:
+ Normal storage of blood results in progressive reductions in
concentrations of 2, 3 DPG in erythrocytes resulting in
increased affinity of Hb for oxygen. This results in the shift of
'ODO to the left which could jeopardize tissue O2 delivery,
particularly in the presence of anemia. The high pH of CPD
anticoagulant, as compared to ACD anticoagulant, prevents
rapid depletion of 2,3 DPG concentration in erythrocytes,
The P50 of CPD preserved blood is maintained at near
normal levels for 1st 2 weeks of storage.
Citrate intoxication:
Hypocalcaemia:
+ Citrate intoxication is not caused by the citrate ion per se, but
because citrate binds calcium.
+ Manifestations of hypocalcaemia due to citrate intoxication
include hypotension and prolonged Q-T intervals in ECG;
reflecting mobilization of Ca2+ stores in bone and the ability
of liver to metabolize citrate to bicarbonate rapidly.
+ The rate of whole blood transfusion in adults has exceeded
150m1/70kg/minute or 1 unit of whole blood in 5 mins before
reduction in plasma ionized calcium can be documented,
Therefore arbitrary administration of calcium is not indicated
+ Although hypocalcaemia due to citrate intoxication is unlikely
in adults the same is not true of neonates receiving blood
transfusion and supplemental calcium may be necessary.
+ In the presence of hypothermia or marked liver dysfunction
the ability to metabolize citrate to bicarbonate may be
reduced
+ The usual dose of calcium chloride is 3-6mg/kg administered
over 5-15 mins with continuous ECG monitoring.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
A) Hepatitis:
+ Remains the infection most frequently transmitted by blood and its
products. Icteric hepatitis develops 50-180 days after a blood
transfusion and has a variable clinical course, ranging from being
asymptomatic to being fatal.
Diagnosis by:
+ Observation between 14 to 180 days transfusion of 2 consecutive
elevations (minimum of 14 days apart) of recipients ALT.
+ Diagnosis of hepatitis B includes appearance of hepatitis B surface
antigen; the hepatitis B surface or core antibody.
+ The absence of serological markers indicative of acute hepatitis A or B
in the presence of liver enzymes abnormalities are taken as
presumptive evidence of “non-A-non B” viral hepatitis, now called
hepatitis ‘C’, the most common causative agent of post transfusion
hepatitis.
- Precautions taken to avoid hepatitis transmission are exclusion of
blood with elevated serum alanine aminotransferase (ALT) or
presence of Abs to hepatitis Bis antigen.
b) Acquired immunodeficiency syndrome (AIDS):
+ Risk of AIDS from blood transfusion is very low, owing to the treating of
donor units for the Ab to the human immunodeficiency virus. However
the infections period does occur during the 12 weeks necessary for HIV
seroconversion. Some infected individuals have a much greater latency
Period (35 months).
Decreased 2, 3 diphosphoglycerate:
+ Normal storage of blood results in progressive reductions in
concentrations of 2, 3 DPG in erythrocytes resulting in
increased affinity of Hb for oxygen. This results in the shift of
'ODO to the left which could jeopardize tissue O2 delivery,
particularly in the presence of anemia. The high pH of CPD
anticoagulant, as compared to ACD anticoagulant, prevents
rapid depletion of 2,3 DPG concentration in erythrocytes,
The P50 of CPD preserved blood is maintained at near
normal levels for 1st 2 weeks of storage.
Citrate intoxication:
Hypocalcaemia:
+ Citrate intoxication is not caused by the citrate ion per se, but
because citrate binds calcium.
+ Manifestations of hypocalcaemia due to citrate intoxication
include hypotension and prolonged Q-T intervals in ECG;
reflecting mobilization of Ca2+ stores in bone and the ability
of liver to metabolize citrate to bicarbonate rapidly.
+ The rate of whole blood transfusion in adults has exceeded
150m1/70kg/minute or 1 unit of whole blood in 5 mins before
reduction in plasma ionized calcium can be documented,
Therefore arbitrary administration of calcium is not indicated
+ Although hypocalcaemia due to citrate intoxication is unlikely
in adults the same is not true of neonates receiving blood
transfusion and supplemental calcium may be necessary.
+ In the presence of hypothermia or marked liver dysfunction
the ability to metabolize citrate to bicarbonate may be
reduced
+ The usual dose of calcium chloride is 3-6mg/kg administered
over 5-15 mins with continuous ECG monitoring.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
A) Hepatitis:
+ Remains the infection most frequently transmitted by blood and its
products. Icteric hepatitis develops 50-180 days after a blood
transfusion and has a variable clinical course, ranging from being
asymptomatic to being fatal.
Diagnosis by:
+ Observation between 14 to 180 days transfusion of 2 consecutive
elevations (minimum of 14 days apart) of recipients ALT.
+ Diagnosis of hepatitis B includes appearance of hepatitis B surface
antigen; the hepatitis B surface or core antibody.
+ The absence of serological markers indicative of acute hepatitis A or B
in the presence of liver enzymes abnormalities are taken as
presumptive evidence of “non-A-non B” viral hepatitis, now called
hepatitis ‘C’, the most common causative agent of post transfusion
hepatitis.
- Precautions taken to avoid hepatitis transmission are exclusion of
blood with elevated serum alanine aminotransferase (ALT) or
presence of Abs to hepatitis Bis antigen.
b) Acquired immunodeficiency syndrome (AIDS):
+ Risk of AIDS from blood transfusion is very low, owing to the treating of
donor units for the Ab to the human immunodeficiency virus. However
the infections period does occur during the 12 weeks necessary for HIV
seroconversion. Some infected individuals have a much greater latency
Period (35 months).
[Massive Blood Transfusion.Continuation:
The other infections that can be transmitted
through blood transfusion are;
Viral:
Cytomegalovirus - Epstein barr virus
Herpes simplex - Measles
Bacterial:
Brucella - Pseudomonas
Salmonella - Shigella
Parasitic:
Microfilaria - Plasmodium
Trypanosoma
Infectious disease testing for blood transfusions:
1. Hepatitis (antibody)
2. Ab to hepatitis B core Ag
3. HIV
4. HIV2
5. HIV Ag (P&H Ag)
6. HTLV WI
7. Serological tests for syphilis
IV. Micro-aggregate infusion
+ Microaggregates consisting of platelets and
leucocytes form during storage of whole blood
Accumulation of these microaggregates
become significant after 2-Sdays and can
cause post transfusion pulmonary dysfunction.
+ Micropore filters have been developed to
remove particles with diameter in the 10
micron to 404 range. Micropore fitters are not
necessary for whole blood < 3 days old
Dr Azam's Notes in Anesthesiology 2013
‘Table 3—Elemental Cal
Dr Azam's Notes in Anesthesiology 2013
78
The other infections that can be transmitted
through blood transfusion are;
Viral:
Cytomegalovirus - Epstein barr virus
Herpes simplex - Measles
Bacterial:
Brucella - Pseudomonas
Salmonella - Shigella
Parasitic:
Microfilaria - Plasmodium
Trypanosoma
Infectious disease testing for blood transfusions:
1. Hepatitis (antibody)
2. Ab to hepatitis B core Ag
3. HIV
4. HIV2
5. HIV Ag (P&H Ag)
6. HTLV WI
7. Serological tests for syphilis
IV. Micro-aggregate infusion
+ Microaggregates consisting of platelets and
leucocytes form during storage of whole blood
Accumulation of these microaggregates
become significant after 2-Sdays and can
cause post transfusion pulmonary dysfunction.
+ Micropore filters have been developed to
remove particles with diameter in the 10
micron to 404 range. Micropore fitters are not
necessary for whole blood < 3 days old
Dr Azam's Notes in Anesthesiology 2013
‘Table 3—Elemental Cal
Dr Azam's Notes in Anesthesiology 2013
78
25. Coagulation & Anesthesia. Dr Azam's Notes in Anesthesiology 2013
COAGULATION SYSTEM AND PATHWAY mun rp vee
~The process of blood coagulation sof paramount ; 7
importance to survival. The blood clotting and subsequent .
dissolution of clot following repair of the injured tissue is Curación: Seser POLE Per
termed hemostasis. y
+ Hemostasis has 4 major events Protslets Acibation of coagulation
1. Vasoconstriction - This causes obliteration of vessel Loose plotele obgregates
lumen caused by serotonin and vasoconstrictors from v2 Tene
platelets.
2. Platelet activation to form platelet plug
3. Fibrin mesh formation due to coagulation pathway Temporary hemostaic plug
activation. pp. DEFINITE HEMOSTATIC
4, Clotdissolution by plasmin after tissue repair. ews
Platelet and Platelet activation: Platelet aggregation inhibition: PGE2, PGI2 and NO
+ Vascular injury disrupts single layer of endothelial cells lining Coagulation cascade:
blood vessels exposing subendothelial proteins consisting of Essential features:
Fibrin
collagen, von Willebrand factor (vWf) and fibronectin. 1. Cascade system where precursor zymogen is converted to active
+ These act as sites for attachment of platelets. Glycoprotein enzyme
1b on the surface of platelets makes adhesion of platelets to 2. Rapid response due to amplification of response.
Wt possible. 3. Limited in response in terms of location and duration due to
+ Platelets are activated by collagen and thrombi. Activation of 1. Quiescent vascular endothelial cells
platelets causes release of arachidonic acid by 2. Negative feedback loops
Phospholipase A2. This is converted to thromboxane A2 3. Decrease in substrate
(TXA2) by Cyclooxygenase. Activated platelets also secrete Concentration by consumption
ADP, TXA2 and ADP also activate platelets. + Inhibition of coagulation enzymes after they are formed
«These causes platelet to change shape to form long + Coagulation pathway (Fig.2) lead to fibrin clot formation through the
psoudopodia, Integrin 1183 on the surface along with intrinsic pathway or extrinsic pathway. These finally converge into
pseudopodia fibrinogen and vWf links adjacent platelets ‘Common pathway.
together to form platelet plug.
Inhibition of platelet aggregation
+ PGE2, PGI and Nitric oxide secreted by the vascular
‘endothelium inhibits platelet aggregation.
+ Prevention of linking of platelets by internalization of a11 to
B3.
79
Dr Azam's Notes in Anesthesiology 2013
COAGULATION SYSTEM AND PATHWAY mun rp vee
~The process of blood coagulation sof paramount ; 7
importance to survival. The blood clotting and subsequent .
dissolution of clot following repair of the injured tissue is Curación: Seser POLE Per
termed hemostasis. y
+ Hemostasis has 4 major events Protslets Acibation of coagulation
1. Vasoconstriction - This causes obliteration of vessel Loose plotele obgregates
lumen caused by serotonin and vasoconstrictors from v2 Tene
platelets.
2. Platelet activation to form platelet plug
3. Fibrin mesh formation due to coagulation pathway Temporary hemostaic plug
activation. pp. DEFINITE HEMOSTATIC
4, Clotdissolution by plasmin after tissue repair. ews
Platelet and Platelet activation: Platelet aggregation inhibition: PGE2, PGI2 and NO
+ Vascular injury disrupts single layer of endothelial cells lining Coagulation cascade:
blood vessels exposing subendothelial proteins consisting of Essential features:
Fibrin
collagen, von Willebrand factor (vWf) and fibronectin. 1. Cascade system where precursor zymogen is converted to active
+ These act as sites for attachment of platelets. Glycoprotein enzyme
1b on the surface of platelets makes adhesion of platelets to 2. Rapid response due to amplification of response.
Wt possible. 3. Limited in response in terms of location and duration due to
+ Platelets are activated by collagen and thrombi. Activation of 1. Quiescent vascular endothelial cells
platelets causes release of arachidonic acid by 2. Negative feedback loops
Phospholipase A2. This is converted to thromboxane A2 3. Decrease in substrate
(TXA2) by Cyclooxygenase. Activated platelets also secrete Concentration by consumption
ADP, TXA2 and ADP also activate platelets. + Inhibition of coagulation enzymes after they are formed
«These causes platelet to change shape to form long + Coagulation pathway (Fig.2) lead to fibrin clot formation through the
psoudopodia, Integrin 1183 on the surface along with intrinsic pathway or extrinsic pathway. These finally converge into
pseudopodia fibrinogen and vWf links adjacent platelets ‘Common pathway.
together to form platelet plug.
Inhibition of platelet aggregation
+ PGE2, PGI and Nitric oxide secreted by the vascular
‘endothelium inhibits platelet aggregation.
+ Prevention of linking of platelets by internalization of a11 to
B3.
79
Dr Azam's Notes in Anesthesiology 2013
[Coagulation & Anesthesia.Continuation: Dr Azam's Notes in Anesthesiology 2013
(Be Paty
Vascular endothelial
xl — Xt ay
x xia Tissue factor/
WE. im Vi complex
x xe €
x xs ya | Protromtinase complex
o
na
Fbinogen ——» Fibrin monomer —Y—» Cross-inked fibrin
Figure 56-1 Depiction ofthe classic coagulation cascade incorporating extrinsic and intrinsic pathways of coagulation From Slaughter TF: The coagulation
system ond cardiac surgery. In Estofanous FG, Barash PG, Reves eds} Cordlac Anesthesia: Princes and Cinical Practice, 2nd ed. Philadelpho, Lippincott
Wilioms & Wilkins, 2001, p 320, wth permission )
Coagulation involves different proteins INTRINSIC PATHWAY:
1. Zymogens + Itis so called because all the necessary protein components are present in plasma. This can
2. Cofactors occur without tissue injury (e.g. abnormal vessel wall)
3. Fibrinogen + The first part is called the contact phase, carried out by Factor XII, Prekallikrein and High
4. Transglutaminase molecular weight kininogen (HMW Kininogen). Activation of factor XII to Xlla in vivo is by
exposed collagen and negatively charged phospholipids and in vitro by negatively charged
particles like Kaolin, glass, dextran sulphate, etc.
+ Factor XIla a serine protease, activates factor XI to Xla and prekallikrein to kallikrein.
Kallikrein in turn activates factor XII to XIla. This is called reciprocal activation.
+ Factor Xla activates factor IX to IXa which requires Ca2+, Factor IXA, Ca2+, X and factor
Villa from a complex known as tenase complex, which converts factor X to Xa which forms
the entry point into common pathway. Here factor Villa acts as a receptor for IX and X andis
called cofactor.
Dr Azam's Notes in Anesthesiology 2013
(Be Paty
Vascular endothelial
xl — Xt ay
x xia Tissue factor/
WE. im Vi complex
x xe €
x xs ya | Protromtinase complex
o
na
Fbinogen ——» Fibrin monomer —Y—» Cross-inked fibrin
Figure 56-1 Depiction ofthe classic coagulation cascade incorporating extrinsic and intrinsic pathways of coagulation From Slaughter TF: The coagulation
system ond cardiac surgery. In Estofanous FG, Barash PG, Reves eds} Cordlac Anesthesia: Princes and Cinical Practice, 2nd ed. Philadelpho, Lippincott
Wilioms & Wilkins, 2001, p 320, wth permission )
Coagulation involves different proteins INTRINSIC PATHWAY:
1. Zymogens + Itis so called because all the necessary protein components are present in plasma. This can
2. Cofactors occur without tissue injury (e.g. abnormal vessel wall)
3. Fibrinogen + The first part is called the contact phase, carried out by Factor XII, Prekallikrein and High
4. Transglutaminase molecular weight kininogen (HMW Kininogen). Activation of factor XII to Xlla in vivo is by
exposed collagen and negatively charged phospholipids and in vitro by negatively charged
particles like Kaolin, glass, dextran sulphate, etc.
+ Factor XIla a serine protease, activates factor XI to Xla and prekallikrein to kallikrein.
Kallikrein in turn activates factor XII to XIla. This is called reciprocal activation.
+ Factor Xla activates factor IX to IXa which requires Ca2+, Factor IXA, Ca2+, X and factor
Villa from a complex known as tenase complex, which converts factor X to Xa which forms
the entry point into common pathway. Here factor Villa acts as a receptor for IX and X andis
called cofactor.
Dr Azam's Notes in Anesthesiology 2013
[Coagulation & Anesthesia.Continuation:
EXTRINSIC PATHWAY:
+ Initiation of fibrin clot formation in response to tissue injury is
called extrinsic pathway. Tissue factor or factor VII is
responsible for extrinsic pathway, so called because tissue
factor (TF) is not present in plasma, but supplied by vascular
endothelial cells and leukocytes. After release of tissue factor
it binds with factor VII which is then activated to TF-Vila by
thrombin, Xlla, IXa. TF — Vil a complex converts factor X to
Xa
FINAL COMMON PATHWAY:
+ Factor Xa formed by extrinsic and intrinsic pathways activate
prothrombin to thrombin. This is prothrombinase complex
Which consists of platelet surface complex which consists of
platelet surface complex which consists of platelet surface
Phospholipids, Ca2+, Factor Va factor Xa and prothrombin.
Thrombin a serine protease converts fibrinogen to fibrin
monomer. The fibrin monomers undergo polymerization
which leads to fibrin clot. Thrombin also converts factor XIII
to Xilla which cause cross linking of fibrin monomers to form
stable fibrin clot.
+ In the revised model of coagulation factor Vila — TF complex
is thought to initiate coagulation rather than contact phase.
After an initial burst of Xa and thrombin, tissue factor
pathway inhibitor dampens Vila/TF pathway. Vila — TF also
activates factor IX to IXa. So it is now thought that Vila - TF
complex is the principal initiator of coagulation, whereas in
the intrinsic pathway is necessary to sustain coagulation
response. This is because, no bleeding was observed in
contact factor deficiencies (factor XII, Prekallikrein, HMW
Kininogen) but bleeding was observed in Factor XI deficient
patients.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Vitamin K dependent clotting factors:
+ They are factors, Il, VII, IX, X. They are synthesized in the liver and
undergo post translational modification by y carboxylation. This is
carried out by vitamin K dependent y glutamyl carboxylase. Coumarin
anticoagulants block this.
Anti clotting mechanism:
‘Two ways:
1. Limiting coagulation cascade
2. Fibrinolytic system
Control of coagulation cascade
{tis by anti coagulant proteins. These include:
i) Protein O
ii) Protein S
ii) Antithrombin II
iv) Thrombomodulin
v) A2 macroglobulin
vi) Heparin cofactor II
vii) Tissue factor pathway inhibitor
+ Antithrombin I (ATII) is the important inhibitor of thrombin, factor IXa,
Xa, Xla, Xlla. Itis greatly augmented by heparin and heparin sulphate
present in vascular endothelium. AT ill is called heparin cofactor.
+ Protein C (Fig. 3) together with thrombomodulin (TM) and protein S act
as an important negative feedback loop. TM is a protein present on the
surface of quiescent vascular endothelial cells. TM binds with thrombin.
This activates protein C. Activated protein C (APC) inactivates Villa and
Va. Protein S potentiates protein C.
Thrombin + Thrombomodulin
Protein C —Ÿ + Activated protein C
Villa ——» Inactive Villa Va ——+* Inactive Va
Regulation of protein C
at
EXTRINSIC PATHWAY:
+ Initiation of fibrin clot formation in response to tissue injury is
called extrinsic pathway. Tissue factor or factor VII is
responsible for extrinsic pathway, so called because tissue
factor (TF) is not present in plasma, but supplied by vascular
endothelial cells and leukocytes. After release of tissue factor
it binds with factor VII which is then activated to TF-Vila by
thrombin, Xlla, IXa. TF — Vil a complex converts factor X to
Xa
FINAL COMMON PATHWAY:
+ Factor Xa formed by extrinsic and intrinsic pathways activate
prothrombin to thrombin. This is prothrombinase complex
Which consists of platelet surface complex which consists of
platelet surface complex which consists of platelet surface
Phospholipids, Ca2+, Factor Va factor Xa and prothrombin.
Thrombin a serine protease converts fibrinogen to fibrin
monomer. The fibrin monomers undergo polymerization
which leads to fibrin clot. Thrombin also converts factor XIII
to Xilla which cause cross linking of fibrin monomers to form
stable fibrin clot.
+ In the revised model of coagulation factor Vila — TF complex
is thought to initiate coagulation rather than contact phase.
After an initial burst of Xa and thrombin, tissue factor
pathway inhibitor dampens Vila/TF pathway. Vila — TF also
activates factor IX to IXa. So it is now thought that Vila - TF
complex is the principal initiator of coagulation, whereas in
the intrinsic pathway is necessary to sustain coagulation
response. This is because, no bleeding was observed in
contact factor deficiencies (factor XII, Prekallikrein, HMW
Kininogen) but bleeding was observed in Factor XI deficient
patients.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Vitamin K dependent clotting factors:
+ They are factors, Il, VII, IX, X. They are synthesized in the liver and
undergo post translational modification by y carboxylation. This is
carried out by vitamin K dependent y glutamyl carboxylase. Coumarin
anticoagulants block this.
Anti clotting mechanism:
‘Two ways:
1. Limiting coagulation cascade
2. Fibrinolytic system
Control of coagulation cascade
{tis by anti coagulant proteins. These include:
i) Protein O
ii) Protein S
ii) Antithrombin II
iv) Thrombomodulin
v) A2 macroglobulin
vi) Heparin cofactor II
vii) Tissue factor pathway inhibitor
+ Antithrombin I (ATII) is the important inhibitor of thrombin, factor IXa,
Xa, Xla, Xlla. Itis greatly augmented by heparin and heparin sulphate
present in vascular endothelium. AT ill is called heparin cofactor.
+ Protein C (Fig. 3) together with thrombomodulin (TM) and protein S act
as an important negative feedback loop. TM is a protein present on the
surface of quiescent vascular endothelial cells. TM binds with thrombin.
This activates protein C. Activated protein C (APC) inactivates Villa and
Va. Protein S potentiates protein C.
Thrombin + Thrombomodulin
Protein C —Ÿ + Activated protein C
Villa ——» Inactive Villa Va ——+* Inactive Va
Regulation of protein C
at
[Coagulation & Anesthesia.Continuation:
+ Heparin Cofactor Il- This inhibits thrombin. It is potentiated
many fold by heparin.
+ Tissue factor pathway inhibitor or lipoprotein associated
coagulation inhibitor (LAC1) inhibits VIIA-TF.
Fibrinolytic system:
+ Degeneration of fibrin clot is a function of plasmin a serine
protease that circulates as a proenzyme plasminogen.
Conversion of plasminogen to plasmin by plasminogen
activator.
Plasminogen activation occurs through
1. Intrinsic system: Here plasminogen interacts with intrinsic
pathway of blood coagulation to generate plasmin.
Accounts for 15% of fibrinolysis.
2. Extrinsic system: Consists of tissue type plasminogen
activator (t-PA) and urokinase type plasminogen activator
(u-PA). Endothelial cells release T-PA by the action of
thrombin, histamine, bradykinin, shear stress or
vasocclusion.
Fibrin formation and
+
Plasminogen
£ Extrinsic action pathwo y
Intrinsic activation PONY exogenous activation
pathway pathway
e tPA ura
ps Streptökinase
Kallikrein
HMW kininogen — Piasmin
+
Fibrin degradation lot Isis
Plasminogen activation pathway
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
[Carr
. Zymogens of serine [Activation [Function
[protease
Factor XII y binding to collagen, — Xila activates factor
Iso to glass, Kaolin, 1 and prekallikrein
jexran.
“actor XI By xila nverts factor IX to Ka
leed Ca?
Factor X ¡otivated on surface of [Activates prothrombin to
ctivated platelets by rombin
nase complex or by TF-
Ila in presence of Cae
“actor I ‘tivated by EE fibrinogen to
othrombinase complex fibrin
Platelet phosphalipids,
a+, Va & Xa)
actor VIT \ctivated by thrombin, Xa,
fla and IXa
[2 Co factors
Factor VII [Thrombin & Xa lia is a cofactor for
[activating factor X by iXa
actor V ombin & Xa factor for the activation
Prothrombin by factor
a
“actor I factor for factor Vila,
+ dependant
Fibrinogen
FactorT [Thrombin in presence of [Forms Fibrin
if. Transglutamase
Factor XIII
[Thrombin in presence of
ka
bilizes fibrin clot by
nvalent cross links
fable 2: Functional classification of clotting factors.
+ Heparin Cofactor Il- This inhibits thrombin. It is potentiated
many fold by heparin.
+ Tissue factor pathway inhibitor or lipoprotein associated
coagulation inhibitor (LAC1) inhibits VIIA-TF.
Fibrinolytic system:
+ Degeneration of fibrin clot is a function of plasmin a serine
protease that circulates as a proenzyme plasminogen.
Conversion of plasminogen to plasmin by plasminogen
activator.
Plasminogen activation occurs through
1. Intrinsic system: Here plasminogen interacts with intrinsic
pathway of blood coagulation to generate plasmin.
Accounts for 15% of fibrinolysis.
2. Extrinsic system: Consists of tissue type plasminogen
activator (t-PA) and urokinase type plasminogen activator
(u-PA). Endothelial cells release T-PA by the action of
thrombin, histamine, bradykinin, shear stress or
vasocclusion.
Fibrin formation and
+
Plasminogen
£ Extrinsic action pathwo y
Intrinsic activation PONY exogenous activation
pathway pathway
e tPA ura
ps Streptökinase
Kallikrein
HMW kininogen — Piasmin
+
Fibrin degradation lot Isis
Plasminogen activation pathway
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
[Carr
. Zymogens of serine [Activation [Function
[protease
Factor XII y binding to collagen, — Xila activates factor
Iso to glass, Kaolin, 1 and prekallikrein
jexran.
“actor XI By xila nverts factor IX to Ka
leed Ca?
Factor X ¡otivated on surface of [Activates prothrombin to
ctivated platelets by rombin
nase complex or by TF-
Ila in presence of Cae
“actor I ‘tivated by EE fibrinogen to
othrombinase complex fibrin
Platelet phosphalipids,
a+, Va & Xa)
actor VIT \ctivated by thrombin, Xa,
fla and IXa
[2 Co factors
Factor VII [Thrombin & Xa lia is a cofactor for
[activating factor X by iXa
actor V ombin & Xa factor for the activation
Prothrombin by factor
a
“actor I factor for factor Vila,
+ dependant
Fibrinogen
FactorT [Thrombin in presence of [Forms Fibrin
if. Transglutamase
Factor XIII
[Thrombin in presence of
ka
bilizes fibrin clot by
nvalent cross links
fable 2: Functional classification of clotting factors.
[Coagulation & Anesthesia.Continuation:
NAME FUNCTION
Protein C [Activated by thrombin bound to
Ihrombomodulin, degrades Villa and Va
ProteinS [Cofactor for protein C
Thrombomodulin/Protein on the surface of endothelial cells,
inds thrombin which activates protein C.
vwr resent in plasma, subendothelial tissue and
ndothelial cells. Carrier of factor VIII and
rolongs its half life, adhesive protein which
inds platelet to subendothelial tissue.
HMW Kininogen (Carries prekallikrein and factor XI and deliver
them to anionic surfaces
Prekallikrein [Activated by Xlla to Kallikrein which
tivates XII to Xlla
[Table 3: Regulatory and other proteins
ASSESSMENT OF COAGULATION FUNCTION AND
ANESTHETIC MANAGEMENT OF A PATIENT WITH
COAGULATION DISORDERS:
+ Successful surgery depends, in part on adequate hemostatic
ability of the patient. Haemorrhage and thrombosis are two
major problems which affect the outcome of surgery.
Hemostasis depends on vascular integrity, platelet function
and coagulation. Assessment of coagulation function prior to
Surgery is of utmost importance for successful outcome of
surgery. But doing all the tests of coagulation prior to surgery
is not cost effective. So we have to approach every patient in
a stepwise systematic manner and order appropriate tests
whenever necessary,
+ As with any patient, approach to a patient with possible
coagulation disorder should start with a detailed history, as
many a time detection of potential problems in hemostasis
becomes evident in the history itself.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
History:
- History with regard to previous bleeding, petechiae, ecchymoses,
hemarthrosis, family history of bleeding disorders, drug history of use of
aspirin, non steroidal anti-inflammatory drugs, coumarin, heparin or
thrombolytic. History of uremia, liver disease, leukemia,
+ A recent uneventful tooth extraction or a minor surgery will virtually rule
out the possibility of coagulation disorder in the patients.
+ If you get a positive history from a patient, then guidelines to your
approach are as given in Table 4.
[Enquiry [Action to be taken if response Is positive
Past or recent history of [Blood count, coagulation screen
bleeding or bruising
Family history of
leeding
ug history
fartarin
[Blood count, coagulation screen
[Discontinue 72h preoperatively. Use heparin if
ecessary. In emergency reverse with FFP + vit
lAspirin IK
[Discontinue 72h preoperatively. Give platelets if
leeding excessive
[Discontinue 24h preoperatively. Watch for GI
jaemorrhage if anticoagulants used
;ostoperatively.
It positive or doubtful discuss thrombophilia
reening with hematology laboratory. LMW
jeparin should be used in all high risk
ituations.
top 4 weeks prior to elective surgery. For
Non-steroidal anti-
inflammatory drug
Past history or family
history of thrombosis
jestrogen containing
ontraceptive pill mergency surgery use LMW heparin
rophylaxis.
Hormone replacement Adhere scrupulously to normal prophylactic
therapy jeasures.
[Table 4- Enquiries relevant to hemostasis to be made preoperatively
NAME FUNCTION
Protein C [Activated by thrombin bound to
Ihrombomodulin, degrades Villa and Va
ProteinS [Cofactor for protein C
Thrombomodulin/Protein on the surface of endothelial cells,
inds thrombin which activates protein C.
vwr resent in plasma, subendothelial tissue and
ndothelial cells. Carrier of factor VIII and
rolongs its half life, adhesive protein which
inds platelet to subendothelial tissue.
HMW Kininogen (Carries prekallikrein and factor XI and deliver
them to anionic surfaces
Prekallikrein [Activated by Xlla to Kallikrein which
tivates XII to Xlla
[Table 3: Regulatory and other proteins
ASSESSMENT OF COAGULATION FUNCTION AND
ANESTHETIC MANAGEMENT OF A PATIENT WITH
COAGULATION DISORDERS:
+ Successful surgery depends, in part on adequate hemostatic
ability of the patient. Haemorrhage and thrombosis are two
major problems which affect the outcome of surgery.
Hemostasis depends on vascular integrity, platelet function
and coagulation. Assessment of coagulation function prior to
Surgery is of utmost importance for successful outcome of
surgery. But doing all the tests of coagulation prior to surgery
is not cost effective. So we have to approach every patient in
a stepwise systematic manner and order appropriate tests
whenever necessary,
+ As with any patient, approach to a patient with possible
coagulation disorder should start with a detailed history, as
many a time detection of potential problems in hemostasis
becomes evident in the history itself.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
History:
- History with regard to previous bleeding, petechiae, ecchymoses,
hemarthrosis, family history of bleeding disorders, drug history of use of
aspirin, non steroidal anti-inflammatory drugs, coumarin, heparin or
thrombolytic. History of uremia, liver disease, leukemia,
+ A recent uneventful tooth extraction or a minor surgery will virtually rule
out the possibility of coagulation disorder in the patients.
+ If you get a positive history from a patient, then guidelines to your
approach are as given in Table 4.
[Enquiry [Action to be taken if response Is positive
Past or recent history of [Blood count, coagulation screen
bleeding or bruising
Family history of
leeding
ug history
fartarin
[Blood count, coagulation screen
[Discontinue 72h preoperatively. Use heparin if
ecessary. In emergency reverse with FFP + vit
lAspirin IK
[Discontinue 72h preoperatively. Give platelets if
leeding excessive
[Discontinue 24h preoperatively. Watch for GI
jaemorrhage if anticoagulants used
;ostoperatively.
It positive or doubtful discuss thrombophilia
reening with hematology laboratory. LMW
jeparin should be used in all high risk
ituations.
top 4 weeks prior to elective surgery. For
Non-steroidal anti-
inflammatory drug
Past history or family
history of thrombosis
jestrogen containing
ontraceptive pill mergency surgery use LMW heparin
rophylaxis.
Hormone replacement Adhere scrupulously to normal prophylactic
therapy jeasures.
[Table 4- Enquiries relevant to hemostasis to be made preoperatively
[Coagulation & Anesthesia. Continuation:
Test [Normal] Abnormalities [Common causes|
range| Indicated by | of disorder
prolongation
Thrombin time|T4-165) _ Deficiency or | Heparin therapy.
m abnormalities of DIC
fibrinogen,
Inhibition of
thrombin by
heparin or EDPs
Prothrombin [10-145] Deficiency or | Warfarin therapy.
time (PT) inhibition of V, VIl,| Liver disease,
X, prothrombin, | Heparin, DIC,
fibrinogen Vitamin K
deticiency
Partlal [30-408) Deficiency or | Heparin therapy,
hromboplastin| inhibition of Y, VII,| DIC, Hemophilia,
time with IX, X prothrombin,| Christmas
fibrinogen disease, von
Kaolin (PTTK) Willebrand's
disease, liver
disease
Bleeding time [3-8 min] Abnormal platelet |inherited disorders]
formation, of platelet function.
Reduced platelet [Drug induced renal
number fallure. Von
Wilebrand's
disease
Table 5: Screening test for coagulation disorders
Integrity of extrinsic pathway
+ Prothrombin time (PT) measures the integrity of the extrinsic
pathway including factors Vil, the common pathway factors
V, X, prothrombin and fibrinogen. It is expressed in terms of
international Normalized Ratio (INR) which is a method to
standardize the prothrombin time assay.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Patients prothrombin time
INR= Lab control Ist
+ Where ISI is the international sensitivity index which is the calibration
factor of the lab thromboplastin used for the test against a WHO
reference preparation.
Integrity of intrinsic pathway:
+ Activated partial thromboplastin time (aPTT or PTT) measures the
integrity of the intrinsic pathway including factors Vil IX, XI, XII as
well as V, X prothrombin and fibrinogen
Integrity. of final common pathway:
+ Itis measured by thrombin time. It is prolonged in functional
abnormality of fibrinogen and to inhibitors of thrombin activity including
the presence of fibrin degradation products.
Integrity of vascular endothelium, platelet function and number:
+ Measured by doing a bleeding time.
Thromboelastogram:
- Even though this cannot be used as a screening test due to the costs
involved, this gives a rapid complete assessment of all pathways, factor
abnormalities, platelet function and thrombolysis.
If you find an abnormality in the screening tests, individual factor
assays may indicate which factors are deficient and appropriate
replacement materials can be made available before surgery.
+ Even though we know how to correct the coagulation abnormality, there
is no definitive answer as to when to correct the laboratory
abnormalities in coagulation tests. The laboratory abnormalities should
be corrected if there is potential risk of severe haemorrhage; keeping in
mind that the blood products are expensive and can transmit diseases
and that transfusion to correct the coagulation abnormality may end up
in fluid overload
Test [Normal] Abnormalities [Common causes|
range| Indicated by | of disorder
prolongation
Thrombin time|T4-165) _ Deficiency or | Heparin therapy.
m abnormalities of DIC
fibrinogen,
Inhibition of
thrombin by
heparin or EDPs
Prothrombin [10-145] Deficiency or | Warfarin therapy.
time (PT) inhibition of V, VIl,| Liver disease,
X, prothrombin, | Heparin, DIC,
fibrinogen Vitamin K
deticiency
Partlal [30-408) Deficiency or | Heparin therapy,
hromboplastin| inhibition of Y, VII,| DIC, Hemophilia,
time with IX, X prothrombin,| Christmas
fibrinogen disease, von
Kaolin (PTTK) Willebrand's
disease, liver
disease
Bleeding time [3-8 min] Abnormal platelet |inherited disorders]
formation, of platelet function.
Reduced platelet [Drug induced renal
number fallure. Von
Wilebrand's
disease
Table 5: Screening test for coagulation disorders
Integrity of extrinsic pathway
+ Prothrombin time (PT) measures the integrity of the extrinsic
pathway including factors Vil, the common pathway factors
V, X, prothrombin and fibrinogen. It is expressed in terms of
international Normalized Ratio (INR) which is a method to
standardize the prothrombin time assay.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Patients prothrombin time
INR= Lab control Ist
+ Where ISI is the international sensitivity index which is the calibration
factor of the lab thromboplastin used for the test against a WHO
reference preparation.
Integrity of intrinsic pathway:
+ Activated partial thromboplastin time (aPTT or PTT) measures the
integrity of the intrinsic pathway including factors Vil IX, XI, XII as
well as V, X prothrombin and fibrinogen
Integrity. of final common pathway:
+ Itis measured by thrombin time. It is prolonged in functional
abnormality of fibrinogen and to inhibitors of thrombin activity including
the presence of fibrin degradation products.
Integrity of vascular endothelium, platelet function and number:
+ Measured by doing a bleeding time.
Thromboelastogram:
- Even though this cannot be used as a screening test due to the costs
involved, this gives a rapid complete assessment of all pathways, factor
abnormalities, platelet function and thrombolysis.
If you find an abnormality in the screening tests, individual factor
assays may indicate which factors are deficient and appropriate
replacement materials can be made available before surgery.
+ Even though we know how to correct the coagulation abnormality, there
is no definitive answer as to when to correct the laboratory
abnormalities in coagulation tests. The laboratory abnormalities should
be corrected if there is potential risk of severe haemorrhage; keeping in
mind that the blood products are expensive and can transmit diseases
and that transfusion to correct the coagulation abnormality may end up
in fluid overload
[Coagulation & Anesthesia.Continuation:
+ Table 6 shows which coagulation factors are present in which
blood products and Fig.5 shows an outline to the approach
towards a patient with a possible bleeding disorder.
‘Common conditions and guidelines to correct the coagulation
abnormalities.
1) Liver disease
+ In liver disease with coagulation abnormalities, there will be
prolongation of the prothrombin time. The consensus now (to
correct the coagulation abnormality) is that if platelet count is
greater than 80 x 109/L (80,000/-mm3), and bleeding time is
normal, administration of fresh frozen plasma (FFP) is
unnecessary if the INR is < 1.6. These patients can be
managed by giving 10mg Vit. K IM daily x 3 days and
availability of FFP should be ensured in the per operative
period
+ If the INR is greater than 1.8 or if there is thrombocytopenia
or platelet dysfunction, FFP or cryoprecipitate should be
given within 6 hours of the start of surgery.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
[Blood product Main coagulation Uses comments
factors
Fresh frozen brinogen, BO compatible
[plasma (FFP) rothrombin nly should be given
factors, V, X, XI, (contains anti-A.B.
me factor Vill, intibodies) stored at
IX, VIL - 30°C Potential
rce of HIV,
jepatitis viruses
ould be used
thin 30 min of
rapid thawing
(Gryoprecipitate [Fibrinogen \dditional source No ABO antibodies
50-80g/dl) fibrinogen and present
actor Vill (2-Su/ factor Vill in ingle donor but
) ¡assively otential source of
'ansfused patients virus transmission.
source of factor [Useful addition to
AI for mild FP if volume
jemophiliacs or loverload is a
eterozygotes at problem
ist tored at -200C
o correct bleeding Stable for 6 months
ime and permit
irgery in patients
th platelet
orage disease
[Albumin solution — [No coagulation Volume mall isk of virus
factors replacement ansfusion
Piatelet latelets In disorders of ABO compatible
concentrates Jatelet production. Should be used can
In platelet storage [ransmit viruses
isease including CMV
In massively (unless white cell
'ansfused patients (depleted)
lot effective in
immune
rombocyggpenia.
[Table-6: Blood products used for hemostasis
+ Table 6 shows which coagulation factors are present in which
blood products and Fig.5 shows an outline to the approach
towards a patient with a possible bleeding disorder.
‘Common conditions and guidelines to correct the coagulation
abnormalities.
1) Liver disease
+ In liver disease with coagulation abnormalities, there will be
prolongation of the prothrombin time. The consensus now (to
correct the coagulation abnormality) is that if platelet count is
greater than 80 x 109/L (80,000/-mm3), and bleeding time is
normal, administration of fresh frozen plasma (FFP) is
unnecessary if the INR is < 1.6. These patients can be
managed by giving 10mg Vit. K IM daily x 3 days and
availability of FFP should be ensured in the per operative
period
+ If the INR is greater than 1.8 or if there is thrombocytopenia
or platelet dysfunction, FFP or cryoprecipitate should be
given within 6 hours of the start of surgery.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
[Blood product Main coagulation Uses comments
factors
Fresh frozen brinogen, BO compatible
[plasma (FFP) rothrombin nly should be given
factors, V, X, XI, (contains anti-A.B.
me factor Vill, intibodies) stored at
IX, VIL - 30°C Potential
rce of HIV,
jepatitis viruses
ould be used
thin 30 min of
rapid thawing
(Gryoprecipitate [Fibrinogen \dditional source No ABO antibodies
50-80g/dl) fibrinogen and present
actor Vill (2-Su/ factor Vill in ingle donor but
) ¡assively otential source of
'ansfused patients virus transmission.
source of factor [Useful addition to
AI for mild FP if volume
jemophiliacs or loverload is a
eterozygotes at problem
ist tored at -200C
o correct bleeding Stable for 6 months
ime and permit
irgery in patients
th platelet
orage disease
[Albumin solution — [No coagulation Volume mall isk of virus
factors replacement ansfusion
Piatelet latelets In disorders of ABO compatible
concentrates Jatelet production. Should be used can
In platelet storage [ransmit viruses
isease including CMV
In massively (unless white cell
'ansfused patients (depleted)
lot effective in
immune
rombocyggpenia.
[Table-6: Blood products used for hemostasis
[Coagulation & Anesthesia.Continuation:
Read Patient with possible bleeding disorder - Chart from old
notes:
2) Patients on anticoagulants
+ Oral anticoagulants should be stopped at least 72 hours
preoperatively and maintained on heparin during the
perioperative period especially if the oral anticoagulants were
started for prosthetic cardiac values or for recent
thromboembolism. Ideally the therapeutic dose of heparin is
adjusted to maintain aPTT at about double the normal value
of 25 to 30 seconds.
3) Hemophilia
+ For major surgery, in a patient with hemophilia A, a target
concentration of 100% factor Vill is set, to be maintained for
the first 5-7 postoperative day, whereas minor procedures
may be adequately covered by concentration of 50% after
the first day.
+ For hemophilia B, factor IX concentrate is given to maintain a
plasma concentration of 30% of normal during the
perioperative period.
4) Platelet disorders
+ Patients with platelet counts above 50 x 10*/L (50,000/mm®)
do not need prophylactic platelets. If itis less than 50 x 1097
L, prophylactic platelets may be advisable, particularly if the
patient requires transfusion of red cells intraoperatively - as
transfusion of red blood cells lowers the platelet count
probably by increasing the consumption of platelets through
complement activation. If platelet count < 30 x 10°/L (30,000/
mms), then it is advisable to raise the count to 30x10%L pre
‘surgery and then to give platelets in theatre according to
bleeding tendency and to maintain the count above 30 x 10°/
L pre surgery and then to give platelets in theatre according
to bleeding tendency and to maintain the count above 30
x10° Lin the postoperative period
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ For conditions due to increased destruction of platelets - like in immune
thrombocytopenic purpura (ITP), intravenous immunoglobulin and
‘steroids should be given to raise the platelet count.
+ Exposure to antiplatelets drugs will increase the risk of surgical
haemorthage whatever the route of anesthesia. Aspirin should ideally
be stopped one week before surgery and definitely 72 hours prior to
surgery and non steroidal and inflammatory drugs two days prior to
surgery. If for emergency surgery, if aspirin cannot be stopped, bleeding
can be controlled by transfusing platelet rich plasma
Disorders of Hypercoagulability:
+ Patients who undergo prolonged abdominal surgery or surgery to the
legs particularly if they require a period of reduced mobility
postoperatively are at a high risk from venous thrombosis and
embolism. The risk is increased if they have one or more risk factor
given in table 7. These patients require anticoagulant measures during
and / or after surgery with subcutaneous heparin.
[Related to venous stasis [Thrombophilic states
- immobility Hereditary
|. Dehydration Ant. Thrombin Il,
| Cardiac failure Protein C deficiency
|. Stroke Protein S deficiency
| Pelvic obstruction Acquired
| Nephrotic syndrome Lupus anticoagulant
| Varicose veins Paroxysmal noctumal
l Hyper viscosity hemoglobinuria
| Sickle cell disease Pregnancy and Puerperium
| Multifactorial Estrogens
| Age Hormone replacement therapy (?)
| Obesity Surgery-abdominal and hip
|. Sepsis Malignant disease
Major trauma
[Table-7 Risk factors of Thromboembolism
Read Patient with possible bleeding disorder - Chart from old
notes:
2) Patients on anticoagulants
+ Oral anticoagulants should be stopped at least 72 hours
preoperatively and maintained on heparin during the
perioperative period especially if the oral anticoagulants were
started for prosthetic cardiac values or for recent
thromboembolism. Ideally the therapeutic dose of heparin is
adjusted to maintain aPTT at about double the normal value
of 25 to 30 seconds.
3) Hemophilia
+ For major surgery, in a patient with hemophilia A, a target
concentration of 100% factor Vill is set, to be maintained for
the first 5-7 postoperative day, whereas minor procedures
may be adequately covered by concentration of 50% after
the first day.
+ For hemophilia B, factor IX concentrate is given to maintain a
plasma concentration of 30% of normal during the
perioperative period.
4) Platelet disorders
+ Patients with platelet counts above 50 x 10*/L (50,000/mm®)
do not need prophylactic platelets. If itis less than 50 x 1097
L, prophylactic platelets may be advisable, particularly if the
patient requires transfusion of red cells intraoperatively - as
transfusion of red blood cells lowers the platelet count
probably by increasing the consumption of platelets through
complement activation. If platelet count < 30 x 10°/L (30,000/
mms), then it is advisable to raise the count to 30x10%L pre
‘surgery and then to give platelets in theatre according to
bleeding tendency and to maintain the count above 30 x 10°/
L pre surgery and then to give platelets in theatre according
to bleeding tendency and to maintain the count above 30
x10° Lin the postoperative period
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ For conditions due to increased destruction of platelets - like in immune
thrombocytopenic purpura (ITP), intravenous immunoglobulin and
‘steroids should be given to raise the platelet count.
+ Exposure to antiplatelets drugs will increase the risk of surgical
haemorthage whatever the route of anesthesia. Aspirin should ideally
be stopped one week before surgery and definitely 72 hours prior to
surgery and non steroidal and inflammatory drugs two days prior to
surgery. If for emergency surgery, if aspirin cannot be stopped, bleeding
can be controlled by transfusing platelet rich plasma
Disorders of Hypercoagulability:
+ Patients who undergo prolonged abdominal surgery or surgery to the
legs particularly if they require a period of reduced mobility
postoperatively are at a high risk from venous thrombosis and
embolism. The risk is increased if they have one or more risk factor
given in table 7. These patients require anticoagulant measures during
and / or after surgery with subcutaneous heparin.
[Related to venous stasis [Thrombophilic states
- immobility Hereditary
|. Dehydration Ant. Thrombin Il,
| Cardiac failure Protein C deficiency
|. Stroke Protein S deficiency
| Pelvic obstruction Acquired
| Nephrotic syndrome Lupus anticoagulant
| Varicose veins Paroxysmal noctumal
l Hyper viscosity hemoglobinuria
| Sickle cell disease Pregnancy and Puerperium
| Multifactorial Estrogens
| Age Hormone replacement therapy (?)
| Obesity Surgery-abdominal and hip
|. Sepsis Malignant disease
Major trauma
[Table-7 Risk factors of Thromboembolism
[Coagulation & Anesthesia.Continuation: Dr Azam's Notes in Anesthesiology 2013
Points to remember before giving anesthesia Property Unfractionated | Low molecular
+ IM medication are best avoided whenever possible. heparin weight heparin
+ Choice of regional anesthesia especially central neuraxial Moan molecular weight 15 KDa 4.5KDa
blockade is avoided in patients with coagulation failure. : -
+ In general anesthesia, nasal intubation is avoided. [Anti XA /And lla activity 11 81
+ Drugs like Warfarin are highly protein bound drugs andoan inhibition of platelet function Yes No
displace protein bound anesthetic drugs. Bioavailability in low dose 50% 100%
+ Patients may have coexisting liver disease and drug — Hac and fanal —
metabolism would be affected.
+ These patients may have received previous blood 1 Of anti Xa activity
transfusion and so universal precautions should have to be Intravenous thr 2hrs
taken to avoid transmission of HIV and Hepatitis B. [Subcutaneous 2hrs Ahrs
With this knowledge, a patient with coagulation abnormality [Thrombocytopenia High Low
can be efficiently managed during the peri operative period. Risk of hemorhage + Decreased
ANTICOAGULANTS AND REGIONAL ANESTHESIA: ss ee M prolonged ves Yes
+ Increasing number of patients now receive oral anticoagulant eLnralization with protamine| Ai Ania Tally
therapy to reduce the risk of stroke from atrial fibrillation and neutraliza AMAA
other cardiac disorders. It is generally accepted that some partial
regional anesthetic techniques will be hazardous in the Table 8: Comparisons of properties of Unfractionated and low molecular
presence of coagulopathies and anticoagulants. In particular Weight heperin
during central neuraxial blockade (intrathecal, extradural,
caudal anesthesia), bleeding is contained in a space Anticoagulants commonly used are:
restricted by bone. Heparin
+ Un-fractionated heparin
Anticoagulants are used for + Low molecular weight heparin
1. Established venous thromboembolism Coumarins
2. Prophylaxis against deep vein thrombosis. Aspirin
3. Patients with prosthetic heart valves
4. To prevent extension of an arterial thrombus
5. As along term anticoagulation to prevent arterial thrombo-
embolism in patients with large left atrium or atrial
fibrillation.
6. Antiplatelets therapy to reduce the incidence of fatal and
non-fatal myocardial infraction in patients with unstable
angina.
87
Dr Azam's Notes in Anesthesiology 2013
Points to remember before giving anesthesia Property Unfractionated | Low molecular
+ IM medication are best avoided whenever possible. heparin weight heparin
+ Choice of regional anesthesia especially central neuraxial Moan molecular weight 15 KDa 4.5KDa
blockade is avoided in patients with coagulation failure. : -
+ In general anesthesia, nasal intubation is avoided. [Anti XA /And lla activity 11 81
+ Drugs like Warfarin are highly protein bound drugs andoan inhibition of platelet function Yes No
displace protein bound anesthetic drugs. Bioavailability in low dose 50% 100%
+ Patients may have coexisting liver disease and drug — Hac and fanal —
metabolism would be affected.
+ These patients may have received previous blood 1 Of anti Xa activity
transfusion and so universal precautions should have to be Intravenous thr 2hrs
taken to avoid transmission of HIV and Hepatitis B. [Subcutaneous 2hrs Ahrs
With this knowledge, a patient with coagulation abnormality [Thrombocytopenia High Low
can be efficiently managed during the peri operative period. Risk of hemorhage + Decreased
ANTICOAGULANTS AND REGIONAL ANESTHESIA: ss ee M prolonged ves Yes
+ Increasing number of patients now receive oral anticoagulant eLnralization with protamine| Ai Ania Tally
therapy to reduce the risk of stroke from atrial fibrillation and neutraliza AMAA
other cardiac disorders. It is generally accepted that some partial
regional anesthetic techniques will be hazardous in the Table 8: Comparisons of properties of Unfractionated and low molecular
presence of coagulopathies and anticoagulants. In particular Weight heperin
during central neuraxial blockade (intrathecal, extradural,
caudal anesthesia), bleeding is contained in a space Anticoagulants commonly used are:
restricted by bone. Heparin
+ Un-fractionated heparin
Anticoagulants are used for + Low molecular weight heparin
1. Established venous thromboembolism Coumarins
2. Prophylaxis against deep vein thrombosis. Aspirin
3. Patients with prosthetic heart valves
4. To prevent extension of an arterial thrombus
5. As along term anticoagulation to prevent arterial thrombo-
embolism in patients with large left atrium or atrial
fibrillation.
6. Antiplatelets therapy to reduce the incidence of fatal and
non-fatal myocardial infraction in patients with unstable
angina.
87
Dr Azam's Notes in Anesthesiology 2013
[Coagulation & Anesthesia.Continuation:
HEPARIN:
+ Untractionated heparin and low molecular weight heparins
are commonly used. Their properties are given in Table 8.
+ Heparin is now used increasingly to
Reduce the risk of deep vein thrombosis
Reduce the risk of venous thromboembolism.
+ In orthopedic surgery, without prophylaxis, deep vein
thrombosis occur in 50-70% of patients undergoing total hip
replacement, total knee replacement, or hip fractures.
Regional anesthesia and heparin:
+ Spinal bleeding following epidural catheters occurs in
approximately 1:200,000 cases, more common in elderly
women (75%)
+ Removal of epidural catheter is a significant risk factor of
spinal bleeding. 30-60% of clinically important hematomas
‘occurs in this circumstance.
RECOMMENDATIONS:
+ Smallest possible needle used for regional anesthesia
+ Smallest effective dose of aspirin used preoperatively
+ Low molecular weight heparins should be delayed as long as
possible postoperatively, in case of neuraxial anesthesia (12
hours minimum, preferably 24 hours).
+ For central blockade, avoid preoperative administration
+ First dose of subcutaneous heparin is administered after
establishment of block
+ In post operative period, catheter removal should take place
in a period 1 hour before dose of heparin is administered to
just before the administration of next dose i.e., when
anticoagulant activity is at the lowest.
+ One dose may be stopped after removal of catheter.
+ Frequent evaluation of neurological status is done. If
continuous infusions are used for postoperative analgesia,
dilute solutions will be preferable as with them the motor
block will be low and may not affect the neurological
examination.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
- In presence of blood during needle or catheter placement, heparin
therapy is delayed for 24 hours.
+ Single shot spinal anesthesia carries the least risk in central neuraxial
blockade.
+ If the patient is on a standard dose regimen of heparin, anesthesia
must be delayed for 12 hours following last dose if possible.
+ If on a high dose anesthesia is delayed for > 24 hours.
DICOUMAROLS
+ Dicoumarol are Vitamin-K antagonists and inhibit the formation of
factors Il, VII, IX and X. Dicoumarol are stopped about 3-5 days before
surgery and converted to heparin
+ Prothrombin time (PT) is monitored for dicoumarol activity, and
activated partial thromboplastin time (aPTT) is monitored for activity of
heparin.
+ When PT is less than 1.5 times the normal and aPTT is about 55-70
sec. it is considered to be effective weaning from dicoumarol and
effective anticoagulation by heparin.
Regional anesthesia and dicoumarol:
+ As all patients on dicoumarol are converted to heparin preoperatively,
all the recommendations for heparin holds true for patients on
dicoumarol too.
+ Postoperatively dicoumarol are started but, before starting dicoumarol,
or before the drug gets effective, catheter introduced epidurally has to
be removed.
ASPIRIN AND OTHER NON STERIODAL ANTI INFLAMMATORY DRUGS
(NSAIDS)
+ Low dose aspirin therapy about 75mg daily is given for most patients
with coronary artery disease to decrease the risk of platelet aggregation
and embolism.
HEPARIN:
+ Untractionated heparin and low molecular weight heparins
are commonly used. Their properties are given in Table 8.
+ Heparin is now used increasingly to
Reduce the risk of deep vein thrombosis
Reduce the risk of venous thromboembolism.
+ In orthopedic surgery, without prophylaxis, deep vein
thrombosis occur in 50-70% of patients undergoing total hip
replacement, total knee replacement, or hip fractures.
Regional anesthesia and heparin:
+ Spinal bleeding following epidural catheters occurs in
approximately 1:200,000 cases, more common in elderly
women (75%)
+ Removal of epidural catheter is a significant risk factor of
spinal bleeding. 30-60% of clinically important hematomas
‘occurs in this circumstance.
RECOMMENDATIONS:
+ Smallest possible needle used for regional anesthesia
+ Smallest effective dose of aspirin used preoperatively
+ Low molecular weight heparins should be delayed as long as
possible postoperatively, in case of neuraxial anesthesia (12
hours minimum, preferably 24 hours).
+ For central blockade, avoid preoperative administration
+ First dose of subcutaneous heparin is administered after
establishment of block
+ In post operative period, catheter removal should take place
in a period 1 hour before dose of heparin is administered to
just before the administration of next dose i.e., when
anticoagulant activity is at the lowest.
+ One dose may be stopped after removal of catheter.
+ Frequent evaluation of neurological status is done. If
continuous infusions are used for postoperative analgesia,
dilute solutions will be preferable as with them the motor
block will be low and may not affect the neurological
examination.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
- In presence of blood during needle or catheter placement, heparin
therapy is delayed for 24 hours.
+ Single shot spinal anesthesia carries the least risk in central neuraxial
blockade.
+ If the patient is on a standard dose regimen of heparin, anesthesia
must be delayed for 12 hours following last dose if possible.
+ If on a high dose anesthesia is delayed for > 24 hours.
DICOUMAROLS
+ Dicoumarol are Vitamin-K antagonists and inhibit the formation of
factors Il, VII, IX and X. Dicoumarol are stopped about 3-5 days before
surgery and converted to heparin
+ Prothrombin time (PT) is monitored for dicoumarol activity, and
activated partial thromboplastin time (aPTT) is monitored for activity of
heparin.
+ When PT is less than 1.5 times the normal and aPTT is about 55-70
sec. it is considered to be effective weaning from dicoumarol and
effective anticoagulation by heparin.
Regional anesthesia and dicoumarol:
+ As all patients on dicoumarol are converted to heparin preoperatively,
all the recommendations for heparin holds true for patients on
dicoumarol too.
+ Postoperatively dicoumarol are started but, before starting dicoumarol,
or before the drug gets effective, catheter introduced epidurally has to
be removed.
ASPIRIN AND OTHER NON STERIODAL ANTI INFLAMMATORY DRUGS
(NSAIDS)
+ Low dose aspirin therapy about 75mg daily is given for most patients
with coronary artery disease to decrease the risk of platelet aggregation
and embolism.
[Coagulation & Anesthesia.Continuation: Dr Azam's Notes in Anesthesiology 2013
+ Aspirin irreversibly acetylates platelet cyclooxygenase, the Manifestations of complications of regional anesthesia in anti coagulated
enzyme that converts arachidonic acid into prostaglandin patients
endo-peroxidases, which is needed for platelet aggregation. + Hematoma formation and nerve compression are common
+ Because cyclooxygenase is not regenerated in circulation complications, which occur in these patients.
within the life span of platelet, one aspirin affects platelet + In central neuraxial blockade, hematoma is restricted by spinal canal
function for a week. and permanent damage to spinal cord or nerves occurs.
+ Waming signs include localized back pain and signs of nerve
Other NSAIDS and drugs that inhibit platelet function e.g. Vit compression. These signs may be masked by blockade, especially if
E, sulphinpyrazone, dipyridamole, antidepressants, the technique is used in postoperative analgesia
phenothiazines, furosemide, steroids etc, inhibit platelet
function reversibly and for about 24-48 hours.
if emergency surgery is needed, before 8 day period of
stopping aspirin or 2 day period of stopping other drugs
mentioned other than aspirin, 2-5 units/70Kg of platelet
concentrate will bring platelet concentration to a normal. This
may also reduce the risk of hematoma formation after
regional anesthesia,
Low dose aspirin < 650 mg/day allows aspirin to be gone
from the body 24 hours after administration of the last dose.
Because the body makes about 70,000 platelets /ml/day, a
48 hour period is sutficient for platelet aggregation to
become normal and regional anesthesia becomes safe.
Considerable controversy exists in the area of stopping
aspirin before anesthesia. Bedside platelet function test (Ivy
bleeding time) may provide guidance as to safety, should be
< 10 minutes. According to some workers, there are practical
difficulties with standardizing and reproducibility of test and
wide normal range
Dr Azam's Notes in Anesthesiology 2013
+ Aspirin irreversibly acetylates platelet cyclooxygenase, the Manifestations of complications of regional anesthesia in anti coagulated
enzyme that converts arachidonic acid into prostaglandin patients
endo-peroxidases, which is needed for platelet aggregation. + Hematoma formation and nerve compression are common
+ Because cyclooxygenase is not regenerated in circulation complications, which occur in these patients.
within the life span of platelet, one aspirin affects platelet + In central neuraxial blockade, hematoma is restricted by spinal canal
function for a week. and permanent damage to spinal cord or nerves occurs.
+ Waming signs include localized back pain and signs of nerve
Other NSAIDS and drugs that inhibit platelet function e.g. Vit compression. These signs may be masked by blockade, especially if
E, sulphinpyrazone, dipyridamole, antidepressants, the technique is used in postoperative analgesia
phenothiazines, furosemide, steroids etc, inhibit platelet
function reversibly and for about 24-48 hours.
if emergency surgery is needed, before 8 day period of
stopping aspirin or 2 day period of stopping other drugs
mentioned other than aspirin, 2-5 units/70Kg of platelet
concentrate will bring platelet concentration to a normal. This
may also reduce the risk of hematoma formation after
regional anesthesia,
Low dose aspirin < 650 mg/day allows aspirin to be gone
from the body 24 hours after administration of the last dose.
Because the body makes about 70,000 platelets /ml/day, a
48 hour period is sutficient for platelet aggregation to
become normal and regional anesthesia becomes safe.
Considerable controversy exists in the area of stopping
aspirin before anesthesia. Bedside platelet function test (Ivy
bleeding time) may provide guidance as to safety, should be
< 10 minutes. According to some workers, there are practical
difficulties with standardizing and reproducibility of test and
wide normal range
Dr Azam's Notes in Anesthesiology 2013
26, Hemophilia.
Bleeding Disorders:
Hereditary ‘Required
Hemophilia À B pic
[Von willebrands Perioperative anticoagulation
Hisoase
(Afibrinogenemias jlutional thrombocytopenia
Factor Vdeficiency Massive blood transfusion
Protein © Deficiency Drug induced hemorthage/platelet
lysfunction
[Antithrombin I ITP, TTP.
deficiency
itamin K deficiency
[Type of surgery (CPB)
Clinical Features of hemophilia
+ Easy bruising, prolonged bleeding after trauma/surgery
+ Bleeding into joints and skeletal muscle hemorrhages
+ Bleeding into closed spaces can result in compression of
peripheral nerves or vascular or airway obstruction.
+ Intracranial bleed may lead to death
Diagnosis:
+ History of unusual bleeding
+ Laboratory test
Normal platelet count and PT
Prolonged activated PTT
Specifically factor VIIINX/XI deficiency
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Preoperative evaluation and preparation
+ Ask history of unusual bleeding
+ History of hemostatic responses to prior operations (tonsillectomy,
dental extractions)
+ History of drug ingestion (aspirin, oral anticoagulants)
+ On physical examination petechial which suggests thrombocytopenia/
abnormal platelet function/defects in vascular integrity
+ Coagulation tests to be done: BT, CT, PT, APTT, platelet count
thromboelastography, thrombin time.
+ History of coexisting diseases (hepatic, renal) or scheduled surgery
(CPB, liver transplantation) which may alter coagulation.
Premedication:
+ Ideally given orally
+ Im injections avoided
+ Anticholinergic given iv if necessary
+ Correct the factor level up to normal or 100% using desmopressin
0.3ugKg iv
+ Factor VIII concentrates and infusion of 1U/kg which increases plasma
factor Vill level by 0.02U/ml
+ 0.3U/ml factor level gives minimal hemostasis.
+ 0.5U/m! factor level necessary for serious bleeding disorder.
Hemophilia and Coagulation Disorders:
Classification:
+ Hemophilia: Type ‘A’ (X linked recessive disorder) (85%) 1:5000
incidence > Factor VII deficiency
+ Hemophilia: Type ‘B’ (14%) (X linked recessive pattern) >
deficient or defective factor IX
+ Hemophilia: Type ‘C’ (1%) (autosomal disorder) > deficiency in
factor XI
Bleeding Disorders:
Hereditary ‘Required
Hemophilia À B pic
[Von willebrands Perioperative anticoagulation
Hisoase
(Afibrinogenemias jlutional thrombocytopenia
Factor Vdeficiency Massive blood transfusion
Protein © Deficiency Drug induced hemorthage/platelet
lysfunction
[Antithrombin I ITP, TTP.
deficiency
itamin K deficiency
[Type of surgery (CPB)
Clinical Features of hemophilia
+ Easy bruising, prolonged bleeding after trauma/surgery
+ Bleeding into joints and skeletal muscle hemorrhages
+ Bleeding into closed spaces can result in compression of
peripheral nerves or vascular or airway obstruction.
+ Intracranial bleed may lead to death
Diagnosis:
+ History of unusual bleeding
+ Laboratory test
Normal platelet count and PT
Prolonged activated PTT
Specifically factor VIIINX/XI deficiency
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
Preoperative evaluation and preparation
+ Ask history of unusual bleeding
+ History of hemostatic responses to prior operations (tonsillectomy,
dental extractions)
+ History of drug ingestion (aspirin, oral anticoagulants)
+ On physical examination petechial which suggests thrombocytopenia/
abnormal platelet function/defects in vascular integrity
+ Coagulation tests to be done: BT, CT, PT, APTT, platelet count
thromboelastography, thrombin time.
+ History of coexisting diseases (hepatic, renal) or scheduled surgery
(CPB, liver transplantation) which may alter coagulation.
Premedication:
+ Ideally given orally
+ Im injections avoided
+ Anticholinergic given iv if necessary
+ Correct the factor level up to normal or 100% using desmopressin
0.3ugKg iv
+ Factor VIII concentrates and infusion of 1U/kg which increases plasma
factor Vill level by 0.02U/ml
+ 0.3U/ml factor level gives minimal hemostasis.
+ 0.5U/m! factor level necessary for serious bleeding disorder.
Hemophilia and Coagulation Disorders:
Classification:
+ Hemophilia: Type ‘A’ (X linked recessive disorder) (85%) 1:5000
incidence > Factor VII deficiency
+ Hemophilia: Type ‘B’ (14%) (X linked recessive pattern) >
deficient or defective factor IX
+ Hemophilia: Type ‘C’ (1%) (autosomal disorder) > deficiency in
factor XI
Hemophilia.Continuation:
+ Coagulant factor VIII is a plasma protein that has two
components, factor VIII; VWF and factor VIII: © each of
which is under separate genetic control
WWF components serves to adhere platelets to collagen in
the sub-endothelial lower of blood vessels during primary
hemostasis and to carry the factor VIII molecule.
In hemophilia A this factor VIII: C is deficient in quantity or
quality
+ Physiologic events after endothelial interruption in the blood
vessel. The small size of platelets relative to other blood
components results in slower transit in the blood vessel with
resultant margination the process in which the faster mving,
larger components push the platelets toward the walls of the
blood vessel. As a result platelets are in contact with the
surface of the blood vessel and can immediately detect any
break in endothelium. Any endothelial break exposes
platelets to subendothelial structures including collagens and
other activating proteins, which cause the glycoprotein
receptors on the platelets to rapidly adhere to these
substances, This adhesion begins the process of platelet
activation, in which the shape of the platelet is changed and
the contents of the cytoplasmic granule are released. These
substances include factors such as ADP, which further
stimulate platelet aggregation. The platelet plug that is
formed in this process provides initial hemostasis.
+ Activation of factor XIII produces cross polymerization of
loose fibrin to produce firm clot.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ Localization of coagulation and control of primary hemostasis are
controlled by factor thrombosis A2, PG and prostacyclins.
+ TxA2 released at the site of injury and stimulates vasoconstriction ADP
release and platelet aggregation.
+ Prostacyclin is produced by intact endothelial cells and prevents
platelet aggregation and clot formation.
+ Clot localization is maintained by dilution of procoagulants flowing in the
blood the removal of activated factors by the liver the action f circulating
procoagulant inhibitors such as antithrombin II! and protein © and
release of serine protease tissue plasminogen activator (TPA). TPA
digests fibrinogen as well as factors V and VIII initiating the physiologic
process of fibrinolysis and resulting in fibrin degradation (split) products,
which are removed by the mononuclear phagocyte system
Extrinsic Coagulation Pathway:
Tissue Common pathways of
Thromboplastin (111) VII IV Prothrombin (11)
ee | Fibrinogen
u Thrombin Y,
XI > X19 IK IV am
| Soluble fibrin
XI “
Collagen
Fibrin clot
Intrinsic Coagulation pathway
et
+ Coagulant factor VIII is a plasma protein that has two
components, factor VIII; VWF and factor VIII: © each of
which is under separate genetic control
WWF components serves to adhere platelets to collagen in
the sub-endothelial lower of blood vessels during primary
hemostasis and to carry the factor VIII molecule.
In hemophilia A this factor VIII: C is deficient in quantity or
quality
+ Physiologic events after endothelial interruption in the blood
vessel. The small size of platelets relative to other blood
components results in slower transit in the blood vessel with
resultant margination the process in which the faster mving,
larger components push the platelets toward the walls of the
blood vessel. As a result platelets are in contact with the
surface of the blood vessel and can immediately detect any
break in endothelium. Any endothelial break exposes
platelets to subendothelial structures including collagens and
other activating proteins, which cause the glycoprotein
receptors on the platelets to rapidly adhere to these
substances, This adhesion begins the process of platelet
activation, in which the shape of the platelet is changed and
the contents of the cytoplasmic granule are released. These
substances include factors such as ADP, which further
stimulate platelet aggregation. The platelet plug that is
formed in this process provides initial hemostasis.
+ Activation of factor XIII produces cross polymerization of
loose fibrin to produce firm clot.
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ Localization of coagulation and control of primary hemostasis are
controlled by factor thrombosis A2, PG and prostacyclins.
+ TxA2 released at the site of injury and stimulates vasoconstriction ADP
release and platelet aggregation.
+ Prostacyclin is produced by intact endothelial cells and prevents
platelet aggregation and clot formation.
+ Clot localization is maintained by dilution of procoagulants flowing in the
blood the removal of activated factors by the liver the action f circulating
procoagulant inhibitors such as antithrombin II! and protein © and
release of serine protease tissue plasminogen activator (TPA). TPA
digests fibrinogen as well as factors V and VIII initiating the physiologic
process of fibrinolysis and resulting in fibrin degradation (split) products,
which are removed by the mononuclear phagocyte system
Extrinsic Coagulation Pathway:
Tissue Common pathways of
Thromboplastin (111) VII IV Prothrombin (11)
ee | Fibrinogen
u Thrombin Y,
XI > X19 IK IV am
| Soluble fibrin
XI “
Collagen
Fibrin clot
Intrinsic Coagulation pathway
et
[Hemophilia.Continuation:
The levels of factor Vill necessary for hemostasis:
keletal muscle hemorrhage
[Clinical Presentations Factor eight concentrations
(%) of normal
[Spontaneous hemorhage = 3%
joderate trauma 48%
jemarthrosis and deep 015%
lajor surgery 30%
Specific components measured by different coagulation tests:
joratory tests [Normal values 'omponents
easured
(Bleeding time 3-10 minutes —_ Platelet count,
¡ascular integrity
Prothrombin time |10-12seconds |, Il, V, VII & X
Fe y destin th 25-35 seconds |, Il, V, VII, IX, X,
romboplastin time XI, & XII
PTT) "
[Thrombin time P-— 10 seconds _ |, Il
[ACT [80 — 120 seconds Il, Il, V, VII, IX, X,
Xt 8 XII
+ PT is measured by adding tissue from thromboplastin (TP) to
a blood specimen and measuring the time until clot
formation. A normal PT could occur with an abnormal
fibrinogen level. Because the PT is only prolonged if the
fibrinogen level <100mg/d!
+ PTT is performed when partial thromboplastin is added to a
test tube of blood and time is measured until clot forms. This
test can be modified by the addition of the surface activating
factors XII and XI before the addition of the partial
thromboplastin, creating the activated partial thromboplastin
time (aPTT). The aPTT is a faster test than PTT and is a
standard test used in clinical practice
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ ACT also is an accelerated version of PTT and activated by
diatomaceous earth, but less sensitive than aPTT to specific factor
deficiencies.
+ Thrombin time measures conversion of fibrinogen to fibrin, a useful test
to determine both inadequate amounts of fibrinogen as well as
inadequate fibrinogen molecules.
+ Thrombodiastogram measures both speed of clot formation as well as
clot firmness and helpful following transfusion of large quantities of
blood products.
Preoperative evaluation and preparation:
1. Correct the patients coagulation status before surgery.
+ Factor VIII levels of 30% of normal will usually provide adequate
hemostasis. For a major orthopedic procedure, the level should be
corrected to 100% of normal approximately 1 to 2 hours before
procedure. A repeat dose should be given if surgical procedure lasts
more than 1.5 hours or if measured factor VIII levels falls below 40% of
normal.
+ One unit of factor VIII: clotting activity is defined as the amount
present in 1ml of fresh normal, pooled plasma.
+ A single unit of factor VII! clotting activity per kilogram of baby weight
will increase plasma factor Vill levels approximately 2%.
Factor Vill concentrates are very stable at room temperature after
reconstitution and thus are appropriate for infusion use.
But approximately 10-20% of hemophilics will develop an antibody
inhibitor against factor VIII and do not achieve the anticipated response
following factor VIII infusion. But some patients who do not respond
well to bolus injections, a continuous infusion can be effective because
appropriate level of missing factor can be achieved relatively easily by
infusion, because complete inhibition of factor only occurs after 1-2
hours. If the factor is continuously infused, there will always be some
that is circulating, unneutralized and hemostatically active,
The levels of factor Vill necessary for hemostasis:
keletal muscle hemorrhage
[Clinical Presentations Factor eight concentrations
(%) of normal
[Spontaneous hemorhage = 3%
joderate trauma 48%
jemarthrosis and deep 015%
lajor surgery 30%
Specific components measured by different coagulation tests:
joratory tests [Normal values 'omponents
easured
(Bleeding time 3-10 minutes —_ Platelet count,
¡ascular integrity
Prothrombin time |10-12seconds |, Il, V, VII & X
Fe y destin th 25-35 seconds |, Il, V, VII, IX, X,
romboplastin time XI, & XII
PTT) "
[Thrombin time P-— 10 seconds _ |, Il
[ACT [80 — 120 seconds Il, Il, V, VII, IX, X,
Xt 8 XII
+ PT is measured by adding tissue from thromboplastin (TP) to
a blood specimen and measuring the time until clot
formation. A normal PT could occur with an abnormal
fibrinogen level. Because the PT is only prolonged if the
fibrinogen level <100mg/d!
+ PTT is performed when partial thromboplastin is added to a
test tube of blood and time is measured until clot forms. This
test can be modified by the addition of the surface activating
factors XII and XI before the addition of the partial
thromboplastin, creating the activated partial thromboplastin
time (aPTT). The aPTT is a faster test than PTT and is a
standard test used in clinical practice
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ ACT also is an accelerated version of PTT and activated by
diatomaceous earth, but less sensitive than aPTT to specific factor
deficiencies.
+ Thrombin time measures conversion of fibrinogen to fibrin, a useful test
to determine both inadequate amounts of fibrinogen as well as
inadequate fibrinogen molecules.
+ Thrombodiastogram measures both speed of clot formation as well as
clot firmness and helpful following transfusion of large quantities of
blood products.
Preoperative evaluation and preparation:
1. Correct the patients coagulation status before surgery.
+ Factor VIII levels of 30% of normal will usually provide adequate
hemostasis. For a major orthopedic procedure, the level should be
corrected to 100% of normal approximately 1 to 2 hours before
procedure. A repeat dose should be given if surgical procedure lasts
more than 1.5 hours or if measured factor VIII levels falls below 40% of
normal.
+ One unit of factor VIII: clotting activity is defined as the amount
present in 1ml of fresh normal, pooled plasma.
+ A single unit of factor VII! clotting activity per kilogram of baby weight
will increase plasma factor Vill levels approximately 2%.
Factor Vill concentrates are very stable at room temperature after
reconstitution and thus are appropriate for infusion use.
But approximately 10-20% of hemophilics will develop an antibody
inhibitor against factor VIII and do not achieve the anticipated response
following factor VIII infusion. But some patients who do not respond
well to bolus injections, a continuous infusion can be effective because
appropriate level of missing factor can be achieved relatively easily by
infusion, because complete inhibition of factor only occurs after 1-2
hours. If the factor is continuously infused, there will always be some
that is circulating, unneutralized and hemostatically active,
Hemophilia.Continuation:] Dr Azam's Notes in Anesthesiology 2013
2. Factor VII activity is present in FFP and cryoprecipitate: - In addition factor VIII: C and vWF are released from endothelial cells.
FFP: - The half time of this released factor is approximately 12 hours and
+ Prepared from single donor repeated administration of DDAVP will deplete the storage capacity in
+ Contains all plasma proteins and factor Vill the endothelial cells.
+ After blood donation, approximately 200ml of FFP are + If DDAVP is to be used preoperatively the release of plasminogen
extracted. activator by DDAVP mandates the use of EACA as well which is a
+ Factor Vill activity is between 0.7 — 0.9 units of clotting antifiorinolytic.
activity per ml of FFP.
+ FFP may carry AIDS and hepatitis B, C etc., ‘Advantages of Factor Ill :
Advantages [Disadvantages
Indications for FER [Gryopreciptate Readily avalable Tergic reaction
+ Isolated factor deficiency
Long shelf life iyperfibrinogenmias
+ Volume expands/massive blood transfusion
+ Reversal of antithrombin Ill deficiency foun albsiand
+ Selected immune deficiencies
2 Thromboeytopenic purpura Factor Vill concentrates|- Easily stored and [High risk of infection
reconstituted long life,
Cryoprecipitate: known potency
+ It is fraction of plasma that precipitates when FFP is thawed. Monoclonal purified Stability, biologic [Cost (?)
+ Itcontains factor VII safety
Factor Vill: vWF
- Factor XII, fibrinogen
+ 5-12 units of factor VII! clotting activity/m!
Indications:
+ Hemophilia, VWF disease, hypofibrinogenemia uremic
platelet dysfunction
+ It may sensitize the Rh -ve individuals to Rh antigens if the
donor is Rh +ve because of presence of small amounts of
red cell frequents in cryoprecipitate.
+ Synthetic analog of ADH is used to prepare mild and
moderate hemophilias for minor surgery.
+ Intravenous DDAVP will rapidly release preformed. Factor
VIII complex, which leads to a two to threefold increase in
circulating factor VIII within 30-60 minutes of administration.
Dr Azam's Notes in Anesthesiology 2013
2. Factor VII activity is present in FFP and cryoprecipitate: - In addition factor VIII: C and vWF are released from endothelial cells.
FFP: - The half time of this released factor is approximately 12 hours and
+ Prepared from single donor repeated administration of DDAVP will deplete the storage capacity in
+ Contains all plasma proteins and factor Vill the endothelial cells.
+ After blood donation, approximately 200ml of FFP are + If DDAVP is to be used preoperatively the release of plasminogen
extracted. activator by DDAVP mandates the use of EACA as well which is a
+ Factor Vill activity is between 0.7 — 0.9 units of clotting antifiorinolytic.
activity per ml of FFP.
+ FFP may carry AIDS and hepatitis B, C etc., ‘Advantages of Factor Ill :
Advantages [Disadvantages
Indications for FER [Gryopreciptate Readily avalable Tergic reaction
+ Isolated factor deficiency
Long shelf life iyperfibrinogenmias
+ Volume expands/massive blood transfusion
+ Reversal of antithrombin Ill deficiency foun albsiand
+ Selected immune deficiencies
2 Thromboeytopenic purpura Factor Vill concentrates|- Easily stored and [High risk of infection
reconstituted long life,
Cryoprecipitate: known potency
+ It is fraction of plasma that precipitates when FFP is thawed. Monoclonal purified Stability, biologic [Cost (?)
+ Itcontains factor VII safety
Factor Vill: vWF
- Factor XII, fibrinogen
+ 5-12 units of factor VII! clotting activity/m!
Indications:
+ Hemophilia, VWF disease, hypofibrinogenemia uremic
platelet dysfunction
+ It may sensitize the Rh -ve individuals to Rh antigens if the
donor is Rh +ve because of presence of small amounts of
red cell frequents in cryoprecipitate.
+ Synthetic analog of ADH is used to prepare mild and
moderate hemophilias for minor surgery.
+ Intravenous DDAVP will rapidly release preformed. Factor
VIII complex, which leads to a two to threefold increase in
circulating factor VIII within 30-60 minutes of administration.
Dr Azam's Notes in Anesthesiology 2013
[Hemophilia.Continuation]
Intraoperative Management:
1. Iron injections can be safely administered if factor VIII
activity is greater than 30%
2. Sedatives or anticholinergic drug should be given iv routes
3. Regional anesthesia is contraindicated because of concern
of hematoma formation at the regional site. But with proper
management of the coagulation status, regional techniques
can be used successfully.
+ Butin a patient with full stomach, regional technique might
be more appropriate because relative risk of aspiration
+ For a completely elective procedure in hemophiliac patient
GA is better.
+ Manipulation of airway during intubation should not be
performed until appropriate replacement factors have been
administered.
+ Elective laryngoscopy should only be attempted following
preoperative factor correction and achievement of complete
muscle relaxation
+ A smaller than predicted small well lubricated ETT well
lubricated ET Tube to be used for intubation.
+ Avoid nasal intubation because of increased chance of
epistaxis.
+ Carefully face mask is applied to avoid trauma to lips, tongue
or face,
+ Strict asepsis to be maintained
+ Gentle face mask application and ventilation.
+ Coexisting liver diseases is a common complication in
hemophiliac patients because of hepatitis acquired from
previous blood or factor transfusion. So, drugs which are
metabolized by liver should be used with caution,
+ Abalanced intravenous technique is preferable to an inhaled
anaesthetics because of reduced hepatic blood flow
observed in inhaled technique. Halothane is avoided
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ If there is blood loss during surgery, whole fresh blood should be
preferably transfused because it increased O2 carrying capacity and
provides all components of coagulation and also expands the
intravascular volume
+ If there is acute hemolytic transfusion reaction ocours during intra
operative during blood transfusion, immediately stop transfusion and
draw blood from the patient and send to blood bank for further cross
matching. An additional tube of blood should be collected and allowed
to sit undisturbed for 5-10 minutes allowing separation of red cells from
plasma. The presence of free plasma Hb in the serum is diagnostic of a
hemolytic reaction.
If life threatening hemorrhage occurs and patient is having high titre of
antibodies (IgG) against factor Vill, then massive doses of factor Vill
concentrates and plasma pheresis with replacement of factor VIII
should be given and it may be of temporary benefit
Porcine factor VIII may provide hemostasis because of its distinct
antigenecity even in presence of circulating inhibitors,
Alternatively APC activated prothrombin complex concentrates which
contain vitamin K dependent enzymes as well as recombined factor
Villa can be given. These activated coagulants enter coagulation
cascade distal to level of factor VIII and bypass the effects of inhibitor
thrombosis is a possible complication.
During extubation gentle oropharyngeal suction to be done under direct
vision
Post operative Management:
‘Analgesics, containing aspirin/NSAIDs avoided
Antihistamines and antitussives can be inhibit platelet aggregation
and prolong bleeding time. So to be used continuously.
Narcotics paracetamol in titrated dose can be used for pain
If regional blockade with catheter was used for anesthesia, analgesics
can be given through this route.
Factor Vill are supplemented for at least 2 — 4 weeks following
surgery.
6. Postoperatively some surgeries maintain factor VII! level at 80% of
normal for first 4 post operative days, whereas others feel that levels
at least 40% of normal are adequate sa
7. Home infusions of factor VIII concentrates can also be used.
a sp pa
Intraoperative Management:
1. Iron injections can be safely administered if factor VIII
activity is greater than 30%
2. Sedatives or anticholinergic drug should be given iv routes
3. Regional anesthesia is contraindicated because of concern
of hematoma formation at the regional site. But with proper
management of the coagulation status, regional techniques
can be used successfully.
+ Butin a patient with full stomach, regional technique might
be more appropriate because relative risk of aspiration
+ For a completely elective procedure in hemophiliac patient
GA is better.
+ Manipulation of airway during intubation should not be
performed until appropriate replacement factors have been
administered.
+ Elective laryngoscopy should only be attempted following
preoperative factor correction and achievement of complete
muscle relaxation
+ A smaller than predicted small well lubricated ETT well
lubricated ET Tube to be used for intubation.
+ Avoid nasal intubation because of increased chance of
epistaxis.
+ Carefully face mask is applied to avoid trauma to lips, tongue
or face,
+ Strict asepsis to be maintained
+ Gentle face mask application and ventilation.
+ Coexisting liver diseases is a common complication in
hemophiliac patients because of hepatitis acquired from
previous blood or factor transfusion. So, drugs which are
metabolized by liver should be used with caution,
+ Abalanced intravenous technique is preferable to an inhaled
anaesthetics because of reduced hepatic blood flow
observed in inhaled technique. Halothane is avoided
Dr Azam's Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
+ If there is blood loss during surgery, whole fresh blood should be
preferably transfused because it increased O2 carrying capacity and
provides all components of coagulation and also expands the
intravascular volume
+ If there is acute hemolytic transfusion reaction ocours during intra
operative during blood transfusion, immediately stop transfusion and
draw blood from the patient and send to blood bank for further cross
matching. An additional tube of blood should be collected and allowed
to sit undisturbed for 5-10 minutes allowing separation of red cells from
plasma. The presence of free plasma Hb in the serum is diagnostic of a
hemolytic reaction.
If life threatening hemorrhage occurs and patient is having high titre of
antibodies (IgG) against factor Vill, then massive doses of factor Vill
concentrates and plasma pheresis with replacement of factor VIII
should be given and it may be of temporary benefit
Porcine factor VIII may provide hemostasis because of its distinct
antigenecity even in presence of circulating inhibitors,
Alternatively APC activated prothrombin complex concentrates which
contain vitamin K dependent enzymes as well as recombined factor
Villa can be given. These activated coagulants enter coagulation
cascade distal to level of factor VIII and bypass the effects of inhibitor
thrombosis is a possible complication.
During extubation gentle oropharyngeal suction to be done under direct
vision
Post operative Management:
‘Analgesics, containing aspirin/NSAIDs avoided
Antihistamines and antitussives can be inhibit platelet aggregation
and prolong bleeding time. So to be used continuously.
Narcotics paracetamol in titrated dose can be used for pain
If regional blockade with catheter was used for anesthesia, analgesics
can be given through this route.
Factor Vill are supplemented for at least 2 — 4 weeks following
surgery.
6. Postoperatively some surgeries maintain factor VII! level at 80% of
normal for first 4 post operative days, whereas others feel that levels
at least 40% of normal are adequate sa
7. Home infusions of factor VIII concentrates can also be used.
a sp pa
Dr Azamı's Notes in Anesthesiology 2013
[Hemophilia.Continuation:
Correction of factor VIII level:
Single unit of factor VII! clotting activity per kilogram of body
weight will increase plasma factor VII level s approximately
2%.
E.g., to correct a 70kg hemophilia patient with 5% factor VIII
activity to 95% of normal will be
—
==. 70 kg = 3,150 of Factor Vit
Desired factor VIII level-patients factor VIII level
= -xbody weight
Dr Azam's Notes in Anesthesiology 2013
[Hemophilia.Continuation:
Correction of factor VIII level:
Single unit of factor VII! clotting activity per kilogram of body
weight will increase plasma factor VII level s approximately
2%.
E.g., to correct a 70kg hemophilia patient with 5% factor VIII
activity to 95% of normal will be
—
==. 70 kg = 3,150 of Factor Vit
Desired factor VIII level-patients factor VIII level
= -xbody weight
Dr Azam's Notes in Anesthesiology 2013
27. Coagulation Factors]
Table 24.1 The
Factor number
1
u
u
v
vil
vil
x
XI
Xill
ctors.
Descriptive name
Fibrinogen
Prothrombin
Tissue factor
Labile factor
Proconvertin,
Antinaemophilic factor
Christmas factor
Stuart-Prower factor
Plasma thromboplastin antecedent
Hageman (contact) factor
Fibrin-stabilizing factor
Prekallikrein (Fletcher factor)
HMWK (Fitzgerald factor)
HMWK, high molecular weight kininagen.
* Active without proteolytic modiicaton,
Dr Azam's Notes in Anesthesiology 2013
Active form
Fibrin subunit
Serine protease
Receptor/cofactor*
Cofactor
Serine protease
Cofactor
Serine protease
Serine protease
Serine protease
Serine protease
Transglutaminase
Serine protease
Cofactor*
Dr Azam's Notes in Anesthesiology 2013
Table 24.1 The
Factor number
1
u
u
v
vil
vil
x
XI
Xill
ctors.
Descriptive name
Fibrinogen
Prothrombin
Tissue factor
Labile factor
Proconvertin,
Antinaemophilic factor
Christmas factor
Stuart-Prower factor
Plasma thromboplastin antecedent
Hageman (contact) factor
Fibrin-stabilizing factor
Prekallikrein (Fletcher factor)
HMWK (Fitzgerald factor)
HMWK, high molecular weight kininagen.
* Active without proteolytic modiicaton,
Dr Azam's Notes in Anesthesiology 2013
Active form
Fibrin subunit
Serine protease
Receptor/cofactor*
Cofactor
Serine protease
Cofactor
Serine protease
Serine protease
Serine protease
Serine protease
Transglutaminase
Serine protease
Cofactor*
Dr Azam's Notes in Anesthesiology 2013
28. Artificial BloodBlood Substitutes
ARTIFICIAL BLOOD CELLS
+ Artificial blood or blood surrogates is a substance used to mimic
and fulfil some functions of biological blood, usually in the
oxygen-carrying sense.
+ The main aim is to provide an altemative to blood transfusion:
+ Artificial blood does not contain the plasma, red and white cells,
or platelets of human blood, but functions to transport and
deliver oxygen to the body's tissues until the recipient's bone
marrow has regenerated the missing red blood cells
+ Artificial blood can be produced in different ways using synthetic
production, chemical isolation, or recombinant biochemical
technology.
+ Current blood substitutes are either haemoglobin-based oxygen
carriers (HBOCs) or perfluorocarbons (PFCs)
+ While HBOCs utilize haemoglobin, an actual component of red
blood cells, PFCs rely solely on synthetic chemical processes.
COMPOSITION OF ARTIFICIAL BLOOD
+ Perfluoro-octyl bromide - 28%
+ FO-9982 -12%
+ Yolk lecithin -2.4%
+ DSPE- - 0.12%
+ Distilled water + 57.48%
ADVANTAGES OF PERFLUOROCARBONS (PFC) EMULSIONS
+ PFCs do not react with oxygen.
+ PFCs allow easy transportation of the oxygen to the body.
- They allow increased solubility of oxygen in plasma
+ PFCs minimize the effects of factors like pH and temperature in
blood circulation.
Dr Azam’s Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
DISADVANTAGES OF PERFLUOROCARBONS (PFC) EMULSIONS
+ Often causes flu-like symptoms.
+ This is often caused by phagocytosis of the perfluorocarbons emulsion by
the recipient organism's immune system.
+ Unable to remain mixed as aqueous solutions — thus, they must be prepared
as emulsions for use in patients,
+ Adecrease in blood platelet count.
+ PFC products cannot be used by the human body, and must be discarded.
This takes approximately 18-24 months.
+ PFCs absorb oxygen passively, patients must breathe at a linear rate to
ensure oxygenation of tissues.
ADVANTAGES OF HEMOGLOBIN-BASED OXYGEN CARRIERS (HBOCS)-
+ Available in much larger quantities.
+ Can be stored for long durations,
+ Can be administered rapidly without typing or cross-matching blood types.
Can be sterilized via pasteurization.
DISADVANTAGES OF HEMOGLOBIN-BASED OXYGEN CARRIERS
(HBOCS)-
+ Reduced circulation halt-lte
+ Disrupts certain physiological structures, especially the gastrointestinal tract
and normal red blood cell haemoglobin.
+ They release free radicals into the body.
IDEAL CHARACTERISTICS OF ARTIFICIAL BLOOD
1. Safe to use.
2. Compatible in human body.
3. Able to transport and release oxygen where needed
4, Storable and durable for longer time periods.
5. Is free of pathogens and toxins which would produce an immune system
response in the human body.
7
ARTIFICIAL BLOOD CELLS
+ Artificial blood or blood surrogates is a substance used to mimic
and fulfil some functions of biological blood, usually in the
oxygen-carrying sense.
+ The main aim is to provide an altemative to blood transfusion:
+ Artificial blood does not contain the plasma, red and white cells,
or platelets of human blood, but functions to transport and
deliver oxygen to the body's tissues until the recipient's bone
marrow has regenerated the missing red blood cells
+ Artificial blood can be produced in different ways using synthetic
production, chemical isolation, or recombinant biochemical
technology.
+ Current blood substitutes are either haemoglobin-based oxygen
carriers (HBOCs) or perfluorocarbons (PFCs)
+ While HBOCs utilize haemoglobin, an actual component of red
blood cells, PFCs rely solely on synthetic chemical processes.
COMPOSITION OF ARTIFICIAL BLOOD
+ Perfluoro-octyl bromide - 28%
+ FO-9982 -12%
+ Yolk lecithin -2.4%
+ DSPE- - 0.12%
+ Distilled water + 57.48%
ADVANTAGES OF PERFLUOROCARBONS (PFC) EMULSIONS
+ PFCs do not react with oxygen.
+ PFCs allow easy transportation of the oxygen to the body.
- They allow increased solubility of oxygen in plasma
+ PFCs minimize the effects of factors like pH and temperature in
blood circulation.
Dr Azam’s Notes in Anesthesiology 2013
Dr Azam's Notes in Anesthesiology 2013
DISADVANTAGES OF PERFLUOROCARBONS (PFC) EMULSIONS
+ Often causes flu-like symptoms.
+ This is often caused by phagocytosis of the perfluorocarbons emulsion by
the recipient organism's immune system.
+ Unable to remain mixed as aqueous solutions — thus, they must be prepared
as emulsions for use in patients,
+ Adecrease in blood platelet count.
+ PFC products cannot be used by the human body, and must be discarded.
This takes approximately 18-24 months.
+ PFCs absorb oxygen passively, patients must breathe at a linear rate to
ensure oxygenation of tissues.
ADVANTAGES OF HEMOGLOBIN-BASED OXYGEN CARRIERS (HBOCS)-
+ Available in much larger quantities.
+ Can be stored for long durations,
+ Can be administered rapidly without typing or cross-matching blood types.
Can be sterilized via pasteurization.
DISADVANTAGES OF HEMOGLOBIN-BASED OXYGEN CARRIERS
(HBOCS)-
+ Reduced circulation halt-lte
+ Disrupts certain physiological structures, especially the gastrointestinal tract
and normal red blood cell haemoglobin.
+ They release free radicals into the body.
IDEAL CHARACTERISTICS OF ARTIFICIAL BLOOD
1. Safe to use.
2. Compatible in human body.
3. Able to transport and release oxygen where needed
4, Storable and durable for longer time periods.
5. Is free of pathogens and toxins which would produce an immune system
response in the human body.
7
Artificial BloodBlood Substitutes] Dr Azam's Notes in Anesthesiology 2013
- Perfluorocarbons (PFC) based- Perfluorochemicals cannot mix
with blood, therefore emulsions must be made by dispersing
small drops of PFC in water.
+ This liquid is then mixed with antibiotics, vitamins, nutrients and
salts, producing a mixture that contains about 80 different
components, and performs many of the vital functions of natural
blood.
Artificial blood Blood substitute
+ The main purpose of artificial | The main purpose of a blood
blood is to act as normal ‘substitute is to provide
blood in the body, providing | temporary support to the
a long-term solution to blood | circulatory system when
loss or distortion. No working | necessary.
artificial blood has been + Blood substitutes generally
created in the status quo, are focused on the role of
transporting oxygen for
short-term cases such as
blood transfusions or
surgeries.
+ Blood substitutes are
generally simpler since they
are only focused on one of
the several functions of real
blood, Several types of
blood substitutes have been
found including
+ Hemoglobin-based oxygen
carriers Perfluorocarbons
‘emulsion
Dr Azam’s Notes in Anesthesiology 2013
- Perfluorocarbons (PFC) based- Perfluorochemicals cannot mix
with blood, therefore emulsions must be made by dispersing
small drops of PFC in water.
+ This liquid is then mixed with antibiotics, vitamins, nutrients and
salts, producing a mixture that contains about 80 different
components, and performs many of the vital functions of natural
blood.
Artificial blood Blood substitute
+ The main purpose of artificial | The main purpose of a blood
blood is to act as normal ‘substitute is to provide
blood in the body, providing | temporary support to the
a long-term solution to blood | circulatory system when
loss or distortion. No working | necessary.
artificial blood has been + Blood substitutes generally
created in the status quo, are focused on the role of
transporting oxygen for
short-term cases such as
blood transfusions or
surgeries.
+ Blood substitutes are
generally simpler since they
are only focused on one of
the several functions of real
blood, Several types of
blood substitutes have been
found including
+ Hemoglobin-based oxygen
carriers Perfluorocarbons
‘emulsion
Dr Azam’s Notes in Anesthesiology 2013
29. What is recombinant factor Vila? Describe the clinical usage of it?
Dr Azam's Notes in Anesthesiology 2013
+ Recombinant human coagulation Factor Vila (rF Vila),
intended for promoting hemostasis by activating the
extrinsic pathway of the coagulation cascade.
+ Factor VII (formerly known as proconvertin) is one of
the proteins that causes blood to clot in the coagulation
cascade. Itis an enzyme of the serine protease class. A
recombinant form of human factor Vila .
+ Administration approval for uncontrolled bleeding in
hemophilia patients.
+ tis often used unlicensed in severe uncontrollable
bleeding
Physiology:
+ The main role of factor VII (F VII) is to initiate the process
of coagulation in conjunction with tissue factor (TF/tactor
i)
+ Tissue factor is found on the outside of blood vessels -
normally not exposed to the bloodstream. Upon vessel
injury, tissue factor is exposed to the blood and
circulating factor VII.
+ Once bound to TF, FVIl is activated to FVila by different
proteases, among which are thrombin (factor ila), factor
Xa, IXa, Xlla, and the FVlla-TF complex itself
+ The most important substrates for FVIla-TF are Factor X
and Factor IX.
+ The action of the factor is impeded by tissue factor
pathway inhibitor (TFPI), which is released almost
immediately after initiation of coagulation.
+ Factor Vil is vitamin K dependent; it is produced in the
liver.
+ Use of warfarin or similar anticoagulants decreases
hepatic synthesis of FVII
Dr Azam's Notes in Anesthesiology 2013
A summary of the structure and properties of coagulation factor VII is as follows:
1. Synthesis and localization - Synthesized in the liver and circulates in the
plasma as a zymogen
IL. Half-ife - 3-6 hours
III, Molecular weight - 50,000
IV. Structure - Amino-terminal (light chain), carboxy-terminal (heavy chain)
catalytic domain, 2 epidermal growth factor domains
V. Cofactor - Tissue factor
VI. Substrate - Factor Vilafissue factor complex activates factors X and IX
+ Replacement therapy for persons with factor VII deficiency depends on the site
and severity of bleeding and the baseline factor VII activity.
+ Spontaneous hemorrhage or mild trauma, therapeutic factor VII levels of 5-10%
are sufficient to stop bleeding.
+ This level may be achieved by administering plasma at a dose of 5-10 mLikg of
body weight and repeating the dose every 8-12 hours for 1-2 days or major
hemorrhage or surgery, plasma may be administered in a loading dose of 15-20
mLAg and followed by 3-6 mL/kg every 8-12 hours until the surgical wound
heals.
+ This may require 5-7 days of treatment.
Dose: 20 - 90 ugKg
FDA Approved Indications of Factor VII A:
+ Hemophilia A/B with inhibitors - 90 g/kg every 2 hours
+ Congenital factor VII deficiency - 15 0 30 ug/xg every 4 to 6 hours,
+ Acute Hemophilia - 70 - 90 pg/kg every 2 - 8 hours
RCT'S:
+ Body trauma - 200 ug/kg then 100 ug/kg BD
+ Brain Trauma 40 - 100 pg/kg
+ CVS surgery - 50 - 160 pg/kg
+ ICh- 15 - 160 pg/kg
+ Liver transplant 100 - 200 pg/kg
Dr Azam's Notes in Anesthesiology 2013
+ Recombinant human coagulation Factor Vila (rF Vila),
intended for promoting hemostasis by activating the
extrinsic pathway of the coagulation cascade.
+ Factor VII (formerly known as proconvertin) is one of
the proteins that causes blood to clot in the coagulation
cascade. Itis an enzyme of the serine protease class. A
recombinant form of human factor Vila .
+ Administration approval for uncontrolled bleeding in
hemophilia patients.
+ tis often used unlicensed in severe uncontrollable
bleeding
Physiology:
+ The main role of factor VII (F VII) is to initiate the process
of coagulation in conjunction with tissue factor (TF/tactor
i)
+ Tissue factor is found on the outside of blood vessels -
normally not exposed to the bloodstream. Upon vessel
injury, tissue factor is exposed to the blood and
circulating factor VII.
+ Once bound to TF, FVIl is activated to FVila by different
proteases, among which are thrombin (factor ila), factor
Xa, IXa, Xlla, and the FVlla-TF complex itself
+ The most important substrates for FVIla-TF are Factor X
and Factor IX.
+ The action of the factor is impeded by tissue factor
pathway inhibitor (TFPI), which is released almost
immediately after initiation of coagulation.
+ Factor Vil is vitamin K dependent; it is produced in the
liver.
+ Use of warfarin or similar anticoagulants decreases
hepatic synthesis of FVII
Dr Azam's Notes in Anesthesiology 2013
A summary of the structure and properties of coagulation factor VII is as follows:
1. Synthesis and localization - Synthesized in the liver and circulates in the
plasma as a zymogen
IL. Half-ife - 3-6 hours
III, Molecular weight - 50,000
IV. Structure - Amino-terminal (light chain), carboxy-terminal (heavy chain)
catalytic domain, 2 epidermal growth factor domains
V. Cofactor - Tissue factor
VI. Substrate - Factor Vilafissue factor complex activates factors X and IX
+ Replacement therapy for persons with factor VII deficiency depends on the site
and severity of bleeding and the baseline factor VII activity.
+ Spontaneous hemorrhage or mild trauma, therapeutic factor VII levels of 5-10%
are sufficient to stop bleeding.
+ This level may be achieved by administering plasma at a dose of 5-10 mLikg of
body weight and repeating the dose every 8-12 hours for 1-2 days or major
hemorrhage or surgery, plasma may be administered in a loading dose of 15-20
mLAg and followed by 3-6 mL/kg every 8-12 hours until the surgical wound
heals.
+ This may require 5-7 days of treatment.
Dose: 20 - 90 ugKg
FDA Approved Indications of Factor VII A:
+ Hemophilia A/B with inhibitors - 90 g/kg every 2 hours
+ Congenital factor VII deficiency - 15 0 30 ug/xg every 4 to 6 hours,
+ Acute Hemophilia - 70 - 90 pg/kg every 2 - 8 hours
RCT'S:
+ Body trauma - 200 ug/kg then 100 ug/kg BD
+ Brain Trauma 40 - 100 pg/kg
+ CVS surgery - 50 - 160 pg/kg
+ ICh- 15 - 160 pg/kg
+ Liver transplant 100 - 200 pg/kg
Blood & Blood Products.Continuation: Dr Azants Notes in Anesthesiology 2013
100
Dr Azam's Notes in Anesthesiology 2013
100
Dr Azam's Notes in Anesthesiology 2013
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