Blood Transfusion and Reactions Presenter: Dr. Suresh Pradhan Moderator: Dr. Upendra Krishna Regmi
Objectives Blood: components, functions Blood Transfusion: Ten Commandments Different Blood Products: Brief discussion Transfusion Reactions
is considered as river of life, fluid of life, growth & health a specialized type of connective tissue in which living blood cells (formed elements), are suspended in a non living fluid matrix called plasma
cells- Red Blood Cells White Blood Cells Platelets normal blood volume = 65-80 ml/kg plasma = 40-50ml/kg
5 blood and blood transfusions
Hematocrit- the volume percentage ( vol %) of red blood cells in blood is normally 45% (42-52) for men and 40% (37-47) for women PCV or Hct = 3 x Hb Hb = 13-18gm% (M); 11-16gm% (F)
Average blood volumes
Haemoglobin levels to diagnose anaemia at sea level (g/l)
Functions of Blood a vehicular organ that perfuses all other organs blood and interstitial fluid deliver nutrients to cells and remove wastes h emostatic governors are carried to and from appropriate sites
Functions of Blood… Transport Regulation Protection
Functions of Blood… Transport : suspended cells include RBC that carry O 2 p latelets contribute to the hemostatic process chemicals dissolved in plasma (nutrients, waste, hormones) metabolic heat for disposal
Functions of Blood… Regulation : plasma contains pH buffers plasma water absorbs heat plasma solutes maintain osmolality
Functions of Blood… Protection : plasma precursor proteins form blood clot when stimulated suspended WBC attack bacteria and viruses ( body’s defense ) plasma contains antibodies and opsonins for immunity
Blood Groups human red cell membranes are estimated to contain at least 300 different antigenic determinants at least 20 separate blood group antigen systems are known the ABO and the Rh systems are important in the majority of blood transfusions
The ABO System first described by Landsteiner in 1901 ABO blood group typing is determined by the presence or absence of A or B red blood cell (RBC) surface antigens: type A blood has A RBC antigen, type B blood has B RBC antigen, type AB blood has both A and B RBC antigens, and type O blood has neither A nor B RBC antigen present accidental transfusion of ABO-incompatible Blood- Rapid intravenous hemolysis
Blood Group RBC Antigen Serum Antibody % A A Anti B 45 B B Anti A 8 AB A & B - 4 O - Anti A Anti B 43
The Rh System described in 1940 by Landsteiner & Wenier approximately 46 Rhesus group red cell surface antigens patients with the D Rhesus antigen are considered Rh-positive individuals lacking this antigen are called Rh-negative
in contrast to the ABO groups, Rh-negative patients usually develop antibodies against the D antigen only after an Rh-positive transfusion or with pregnancy, in the situation of an Rh-negative mother delivering an Rh-positive baby
Other Red Blood Cell Antigen Systems Other red cell antigen systems include Lewis, P, Ii, MNS, Kidd, Kell , Duffy, Lutheran, Xg , Sid, Cartright , YK, and Chido Rodgers fortunately, with some exceptions ( Kell , Kidd, Duffy, and Ss ), alloantibodies against these antigens rarely cause serious hemolytic reactions
Indications of blood transfusion Blood loss greater than 20% of blood volume Hemoglobin level less than 8 g/ dL Hemoglobin level less than 10 g/ dL with major disease (e.g., emphysema, ischemic heart disease) Hemoglobin level of less than 10 g/ dL with autologous blood Hemoglobin level less than 12 g/ dL and ventilator dependence
whole blood in case of surgical condition during a major operation severe blood loss or hemorrhage post operatively in a severe debilitated and anemic patient as a prophylactic measure preoperatively in hemorrhagic tendencies as in haemophilia , ITP
Clinical judgement- Cardiovascular status nature of surgical/medical illness age anticipated additional blood loss arterial O 2 tension
The Practice Guidelines for Blood component therapy developed by the ASA state that “Red blood cell transfusion is rarely indicated when the haemoglobin concentration is greater than 10 gm/dl and is almost always indicated when it is less than 6 gm/dl”
Transfusion Ten Commandments adapted from the NHS Blood and Transplant ‘Transfusion 10 commandments’ underpin safe and effective transfusion practice Transfusion should only be used when the benefits outweigh the risks and there are no appropriate alternatives.
Results of laboratory tests are not the sole deciding factor for transfusion. Transfusion decisions should be based on clinical assessment underpinned by evidence-based clinical guidelines. Not all anaemic patients need transfusion. (there is no universal ‘transfusion trigger’)
Discuss the risks, benefits and alternatives to transfusion with the patient and gain their consent. The reason for transfusion should be documented in the patient’s clinical record. Timely provision of blood component support in major haemorrhage can improve outcome – good communication and team work are essential.
Failure to check patient identity can be fatal. Patients must wear an ID band (or equivalent) with name, date of birth and unique ID number. Confirm identity at every stage of the transfusion process. Patient identifiers on the ID band and blood pack must be identical. Any discrepancy, DO NOT TRANSFUSE.
The patient must be monitored during the transfusion. Education and training underpin safe transfusion practice.
Blood Products any therapeutic substances that are prepared from human blood Blood Components - red cell concentrates - platelet concentrates - fresh plasma - cryoprecipitate Plasma Derivatives - albumin - coagulation factors - immunoglobulins
Blood Component Therapy process of transfusing only that portion of the blood needed by the patient allows a single unit of donated blood to benefit more than one patient Red blood cells and Platelets are the most frequently transfused blood components
Blood Components
Banked Whole blood no components have been removed consists of red blood cells, white blood cells and platelets in plasma can be stored for 5 weeks stored in the refrigerator , the platelets are useless and factors V & VIII are greatly reduced
Banked Whole blood… 49 ml of CPDA preservative solution is added to 301 ml blood transfusion of whole blood may be necessary certain types of major surgery Acute blood loss > 15% major trauma such as a car accident or gunshot wound requiring emergency surgery
Fresh whole blood blood that is administered within 24 hours of its donation rarely indicated poor source of platelets and factor VIII
Packed Red Cells the red cells from a donor unit, diluted with plasma to a hematocrit of about 75% volume is about 200 mL storing red cells (just above freezing) allows survival for 42 days decreases 2,3-DPG ruins the platelets and neutrophil
Packed Red Cells… Red blood cells contain hemoglobin carries oxygen throughout the body essentially provides oxygen-carrying capacity product of choice for most clinical situations Indications acute trauma before surgery people with anemia who are having surgery
Packed Red Cells… fastest way to increase the oxygen-delivering capacity of the blood a unit of packed red cells will raise the hematocrit by 3% and the hemoglobin by 1-1.5 gm/ dL
Frozen Red Cells reduces the risk of infusing antigens, or foreign bodies, that the body might regard as potentially dangerous Previously sensitized patients not available for use in emergency situations RBC viability is improved ADP and 2,3 DPG maintained
Frozen Red Cells… stored in the frozen state in a hypertonic glycerol solution for up to 10 years indicated for prolonged storage of rare red cells expensive but the chance of reaction & diseases transmission is less Glycerol must be separated from RBC before transfusion
Microaggregate-Free Blood used to prevent reactions to leucocyte and platelet antigens specially designed machines are used to wash the red blood cells (RBCs), which are then suspended in sterile saline
Microaggregate-Free Blood… haematocrit of 70-80% and a volume of about 180ml saline washing removes residual plasma (98%), and reduces the concentration of leucocytes, platelets and cellular debris Stored for 24 hr at 1-6 ˚C
Irradiated Red Cells gamma radiation is used to destroy the lymphocytes in a unit of packed red cells that are responsible for transfusion related graft versus host disease Uses: severely immunocompromised recipients lymphoma stem cell and marrow transplants unborn children undergoing intrauterine transfusion
Leucocyte Depleted Red Cells 99.9% of the white cells removed by freezing or microfiltration reduces, but does not eliminate the risk of cytomegalovirus (CMV), Epstein-Barr, HTLV infections and febrile reactions
Granulocytes indicated for life-threatening infections in neutropenic cancer patients who are unresponsive to antibiotics prepared by separating white blood cells from blood donated by volunteers whose leucocyte count has been increased by pre-treatment with corticosteroids, or those with chronic granulocytic leukaemia
Granulocytes… donations must be cross-matched because they contain large numbers of red blood cells irradiated to remove the lymphocytes collected either by apheresis or derived from whole blood stored for 24 hours at 20-24 ˚C
Platelet Concentrates collection and storage of platelets 1. Pooled platelets 2. Apheresis platelets platelets last for 3-5 days if stored on an agitator at 22˚C and at a pH of between 6.2 and 7.8 each bag has a volume of 250-350ml
Platelet Concentrates… are not usually cross-matched with the recipient, but where possible ABO specific platelets should be used risk of transmission of bacterial infection is higher with platelet transfusions than red cells, particularly if they have been stored for 3 days or more
Platelet Concentrates… bacterial contamination may occur at the time of collection, and the storage bags are made of special plastic, which allows gas exchange (oxygen and carbon dioxide) to occur across its walls at 22˚C this helps preserve platelet function but promotes bacterial growth the longer the platelets are kept prior to transfusion, the higher the risk of bacteremia
Platelet Concentrates… indications in platelet disorders in massive blood loss one unit will usually raise the platelet count 5-10k/microliter check one hour after transfusion
Indications For Platelet Transfusion
Fresh Frozen Plasma used to provide replacement coagulation factors in cases of excessive bleeding from freshly donated blood contains all the coagulation factors and albumin source of plasma cholinesterase only source of factor V
1 unit FFP = 3% increase in CF levels at least 30% to ensure adequate coagulation Indicated for coagulopathy and deficient clotting factors
Indications For The Use Of Fresh Frozen Plasma
Collection And Storage Of FFP FFP is collected as the supernatant after centrifuging a donation of whole blood is frozen within 8 hours and may be stored for up to 1 year at -30 ˚C under these conditions, the loss of Factors V and VIII is kept to a minimum frozen packs are brittle and should be handled with care
frozen plasma can be thawed using a dry oven (10 minutes), microwave (2-3 minutes) or a water bath (20 minutes) thawed FFP is best used immediately, but may be stored at 4˚C and infused within 24 hours, provided it is kept at this temperature or returned to the blood bank for storage within 30 minutes of being removed from a 4˚C fridge or transport box
Cryoprecipitated antihemophilic factor an antihemophilic concentrate prepared from plasma is rich in clotting factors used in people with hemophilia, von Willebrand's disease or other major coagulation abnormalities to prevent or control bleeding
contents are the major portion of the Factor VIII, von Willebrand factor, fibrinogen, Factor XIII and fibronectin present in freshly drawn and separated plasma one unit of plasma typically generates 10 to 20 mL of cryoprecipitate these small concentrates are combined for a single adult dose of five bags and frozen at –20°C
Indications For The Use Of Cryoprecipitate
Plasma Derivatives proteins processed from plasma for therapeutic infusions Albumin Immunoglobulin Clotting factors derivatives are purified from plasma using physicochemical fractionation methods developed by Edwin J. Cohn in the 1930s
Albumin when all the cellular material and coagulation factors have been removed from plasma, it contains mostly albumin available as 5% and 25% (salt poor albumin) solution Albumin is heat-treated to kill viruses Shelf life of 2 years and should be stored at room temperature. used to restore intravascular volume
Immunoglobulins IgGs are given for immune support or for immunomodulation to suppress native antibody production Hyperimmune globulins are fractionated from the plasma of donors with high levels of antibody to specific antigens of interest, such as viruses (HBV, CMV, varicella zoster) or the Rh blood group D antigen ( RhIG to prevent anti-D formation in RhD -negative women)
Fibrin Glue fibrin glue and fibrin gel are blood derivatives rather than pharmacologic agents is derived from a source of fibrinogen and factor XIII (fibrin-stabilizing factor), in which a solution of fibrinogen is mixed with a solution of thrombin and applied to a surgical field applied directly to wounds that display diffuse microvascular bleeding or can be used to seal vascular grafts
Things To Be Considered Before Transfusion checked by two individuals identification with patients name and bag number blood grouping and cross matching date of collection and expiry inspected for bacterial contamination such as discoloration, bubbles, or any suspended particles and clots inside the bag
Things To Be Considered Before Transfusion… warming up of blood to 37 o C rapid transfusion pediatric patients warming may not be necessary if 1 or 2 units of blood are slowly transfused to normothermic adult patients secure IV access preparation of transfusion set a standard blood transfusion set with a pore size of 170 m to trap any clots or debris
initial transfusion (about 15 minutes) should be slow the IV line should be free from calcium containing drugs/fluids
Transfusion Reactions
Immune Complications Infectious Complications Complications related to massive blood transfusion
Immune Complications are due to sensitization of the recipient to the donor red cells white cells platelets plasma proteins less commonly- the transfused cells or serum may mount an immune response against the recipient
Immune Reactions can be divided into: Haemolytic Reactions Non- haemolytic Reactions
Haemolytic Reactions involves specific destruction of the transfused red cells by the recipient’s antibodies can be classified into Acute Haemolytic Reactions Delayed Haemolytic Reactions
Acute Haemolytic Reactions due to ABO incompatibility most common cause- misidentification of patient blood specimen transfusion unit symptoms vary depending upon patient’s conditions
in awake patients- chills, fever, nausea, chest and flank pain in anesthetized patients- rise in temperature unexplained tachycardia hypotension hemoglobinuria diffuse oozing from the surgical site rapid development of- DIC, Shock, Renal failure
Management Of Acute Hemolytic Reaction stop transfusion recheck unit against blood slip and patient identity send blood sample for Hb , repeat compatibility test, coagulation study and platelets count urinary catheterization and send urine for Hb osmotic diuresis- mannitol/ IV fluids
Delayed Haemolytic Reactions also known as extravascular hemolysis usually mild caused by antibodies to non-D antigens of Rh system or to foreign alleles in other systems such as Kell , Duffy, Kidd antigens hemolytic reactions are delayed 2-21 days after the blood transfusion
symptoms- usually mild malaise jaundice fever patients’ Hematocrit fails to rise or rises only transiently inspite of blood transfusion and absence of bleeding serum conjugated bilirubin increases due Hb breakdown
diagnosis- Direct Coombs’ test treatment- primarily supportive
Non- haemolytic Reactions occur due to sensitization of the recipient to the donor’s white cells, platelets or plasma proteins risk of these reactions can be reduced by use of leukoreduced blood products
Different Non-hemolytic Reactions Febrile Reactions Urticarial Reactions Anaphylactic Reactions Transfusion Related Lung Injury (TRALI) Graft Versus Host Disease Post Transfusion Purpura Transfusion Related Immunomodulation
Febrile Reactions white blood cells or platelet sensitization is manifested as febrile reactions relatively common characterized by increase in temperature without evidence of hemolysis patients with history of repeated febrile reactions should receive leukoreduced transfusions only
Urticarial Reactions characterized by erythema hives itching without fever relatively common due to sensitization of the patient to transfused plasma proteins treatment- antihistaminics and steroids
Anaphylactic Reactions relatively rare (1:150,000) are severe reactions may occur after transfusion of only a few ml of blood treatment-epinephrine, fluids, corticosteroids, H 1 & H 2 blockers patients with IgA deficiency should receive thoroughly washed packed red cells, deglycerolized frozen red cells or IgA free blood.
Transfusion Related Lung Injury (TRALI) presents as acute hypoxia and non cardiac pulmonary edema occurring within 6 hours of blood product transfusion frequency- 1:5000 can occur with transfusion of any blood components but specially platelets and FFP transfusion of antileukocytic or anti HLA antibodies results in damage to the alveolar-capillary membrane
treatment: similar to ARDS but response to treatment varies TRALI may resolve within a few days with supportive therapy
Graft Versus Host Disease seen in immunocompromised patients cellular blood products contain lymphocytes capable of mounting an immune response against the compromised (recipient) host irradiation of red cell, granulocyte, and platelet transfusions effectively eliminates lymphocytes without altering the efficacy of such transfusions
Post Transfusion Purpura rarely, profound thrombocytopenia may occur after blood transfusion results due to development of platelet alloantibodes these antibodies destroy the patient’s own platelets platelet count drop precipitously 5-10 days following blood transfusion treatment- IV IgG and Plasmapheresis
Transfusion-Related Immunomodulation diminishes immune responsiveness and promote inflammation recent studies show perioperative transfusion may increase the risk of post operative bacterial infection, cancer recurrence and mortality so unnecessary blood transfusions should be avoided
Infectious Complications viral infections hepatitis- B (1:200,000) , C (1:190,000) AIDS (1:190,000) other viral infections- CMV, EBV, Parvovirus, West Nile Virus
bacterial infections second leading cause of transfusion associated mortality gram positive- Staphylococcus and gram negative- yerisina , citrobacter to avoid possibility if significant bacterial contamination, blood products should be administered over a period shorter than 4 hrs
specific bacterial diseases which are rarely transmitted are: syphilis brucellosis salmonellosis yersiniosis rickettsioses
Massive Blood Transfusion Massive transfusion is defined, in adults, as replacement of total blood volume in 24 hours half of total blood volume in 6 hours one unit blood in 5 mins 5 units blood in 60 mins in children, it is defined as transfusion of >40 mL/kg
Massive transfusion occurs in settings such as severe trauma ruptured aortic aneurysm surgery and obstetrics complications
the goals to the management of massive transfusion include: early recognition of blood loss maintenance of tissue perfusion & oxygenation by restoration of blood volume & haemoglobin arrest of bleeding including with early surgical or radiological intervention, and judicious use of blood component therapy to correct coagulopathy
coagulopathy Dilutional thrombocytopenia Lack of coagulation factors V & VIII DIC associated with hypoperfusion or hemolytic reaction
citrate toxicity calcium binding by citrate- hypocalcemia citrate metabolism is primarily hepatic-patients with hepatic disease or dysfunction (and possibly hypothermic patients) may demonstrate hypocalcemia and require calcium infusion during massive transfusion, as may small children and others with relatively impaired parathyroid–vitamin function
hypothermia all blood products should be warmed to normal body temperature ventricular arrhythmias progressing to fibrillation may occur at 30 o C hypothermia hampers cardiac resuscitation
acid-base balance: metabolic acidosis----as normal tissue perfusion occurs---metabolic acidosis resolves and metabolic alkalosis occurs due to citrate/lactate
Serum Potassium concentration: extracellular concentration of potassium in stored blood increases with time the amount of extracellular potassium transfused with each unit is typically less than 4 mEq per unit Hyperkalemia can develop regardless of the age of the blood when transfusion rates exceed 100 mL/min