mismatched blood transfusion hunkkb final.pptx

Blood

1. MANAGEMENT OF MISMATCHED BLOOD TRANSFUSION AND MASSIVE BLOOD TRANSFUSION Moderator- Dr.Madhusudan [Associate Professor] Presentor-Dr.Ramya 1

2. Introduction Blood is the connective tissue consisting of plasma and cellular components Average human has 5-6 litres of blood that constitute to 8% of total body weight It is the transporting fluid that carries vital substances to all parts of the body 2

3. Properties of the blood Colour- dark red in veins,bright red in arteries Constitute 8% of body mass Ph slightly alkaline 7.34-7.45 Temperature 38c Viscosity-3 to 4 times more viscous tham water Volume -5 to 6 litres Osmolarity -280-300 mosm /l 3

4. PLASMA is the pale yellow coloured liquid component of blood that holds the cellular elements of blood in suspension. The PH of the plasma is 6.8 -7.7 It consists of water(91%) and 9% solids(1% inorganic molecules and 8% organic molecules) . Organic molecules –plasma proteins7% ( albumin,globulin,fibrinogen,prothrombin ). Inorganic molecules –sodium,calcium,chloride,bicarbonates,potassium,magnesium,phosphates,iron,copper. Functions are osmotic balance maintainence , pH buffering, helps in blood clotting . 4

5. RBC Adult male has 5.4million/ microlitre Adult female has 4.8million/ microlitre In infants 6-7 million/cu mm In fetus 7-8 million /cu mm Lifespan is 120 days Helps in transport of gases and buffering of blood pH 5

6. WBC Grouped as granulocytes and agranulocytes . Granulocytes-neutrophils, eosinophils, basophils Agranulocytes -lymphocytes, monocytes Neutrophils-helps in phagocytosis Eosinophils-destroy antigen-antibody complexes,kills parasites,helps in inactivating inflammatory chemicals. Basophils –has heparin ,release histamine and other mediators of inflammation. Lymphocytes-mount immune response by direct cell attack(T-cells) or via antibodies (B-cells). Monocytes – helps in phagocytosis and they develop as macrophages in tissues. Life span is only 18-36 hrs after being released from the marrow 6

7. Platelets Normal count is 1,30,000 – 4,00,000. Life span is 9-10 days. Functions - forms temporary platelet plugs to stop bleeding and initiating the work of plasma based clotting factors such as fibrinogen. Secrete chemicals that attract neutrophils and monocytes to inflammation site. Secrete growth factors that stimulate mitosis in fibroblasts , smooth muscle and help in maintaining blood vessel lining. 7

8. Whole Blood It is fresh and Metabolically active than stored blood Stored at 1-4oc. Shelf life is 35 to 42 days. In first 4-6hours all the components ate present. Platelets fall to less than 1% by 4-48 hours. Labile factor V and VIII also disappear in same time followed by other clotting factors. Potassium levels increase and ATP levels fall 2,3 DPG levels and pH fall after 5-7days of storage 8

9. Packed RBC Obtained by apheresis collection or prepared from anticoagulated whole blood. Following centrifugation,plasma is removed and 100ml of additive solution is added Each unit contains 200ml RBCs , plasma <50ml , hematocrit of 55-60%. Shelf life is 21-42 days. 9

10. INDICATIONS :- Acute blood loss (<1500-2000ml in adult). Paediatric patients. Anemia Thalassemia. 10

11. Platelet concentrates These are obtained either as pooled concentrations from 4-6 whole blood donations or as apheresis concentrated obtained from one donor. If platelets are stored at room temperature ,they can be used up to 7 days after collection. Random donor unit has 55 × 10 9 platelets/unit Apheresis unit has 250 × 10 9 platelets/unit 11

12. Fresh frozen plasma It is the most frequently used plasma product. Produced shortly after donation,generally frozen within 8 to 24 hours. Thawed plasma is stored at 1to 50 c for upto 5 days. CONTENTS :- Factors IV,V,VII,VIII,IX Protein S,C and antithrombin III Electrolytes , albumin , immunoglobulins and complement. 12

13. Each unit of FFP generally increases the level of each clotting factor by 2%-3% in adults. Initial therapeutic dose is 10-15ml/kg. Goal is to achieve 30% of normal coagulation factor concentration. FFP may also be used in patients who received massive blood transfusion and continue to bleed following platelet transfusion 13

14. Cryoprecipitate It is prepared when FFP is thawed and the precipitate is reconstituted. Constituents -1.factorVIIIc( procoagulant activity) 2.von Willebrand factor 3.fibrinogen 4.factor XIII 5.fibronectin which is a glycoprotein that has role in reticuloendothelial clearance of foreign particles and bacteria from blood. 14

15. All the plasma proteins are present in only trace amounts. Should be administered through a filter . Rate of administration should be atleast 200ml/hr. Infusion should be completed within 6hours of thawing. 15

16.               COMPATIBILITY TESTING Includes ABO-Rh typing                  Antibody screen                  Cross matching -Designed to demonstrate harmful antigen-antibody interactions in vitro so that harmful in vivo antigen-antibody interactions can be prevented. -Donor blood must be screened for hemolytic  anti A and/or anti B antibodies and Rh antibodies -Recipient blood must undergo ABO-Rh typing as well as testing for unexpected antibodies -Proper selection of donor blood requires a crossmatch to test for compatibility between recipient and donor blood 16

17.                   ABO-RH TYPING Determination of correct blood type is most important because most serious reactions are usually caused by accidental transfusion of ABO-incompatible blood. 15% of all  transfusion related deaths are related to hemolytic reactions due to antibody incompatibility. 17 BLOOD GROUP Anti -A Anti-B        A           +      _        B           _        +        AB           +        +         O            _        _

18.                Antibody Screening Done to identify unexpected RBC alloantibodies Patient serum is combined with reagent RBC with an additive that promote binding of antibodies to the RBC  The mixture is incubated at 37c ,washed and mixed with reagent containing antibodies to IgG and complement. The reagent binds to any IgG attached to the RBCs,crosslinking the RBCs and producing agglutination in vitro. If the test is positive,follow up testing must be done to identify the target antigen. 18

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20.                 CROSS MATCHING Trial transfusion within a test tube in which donor RBCs are mixed with recipient serum to detect a potiential for transfusion reaction.  The full crossmatch can be completed in 45 to 60 min  Performed in three phases:      Immediate spin phase      Incubation phase      Indirect antiglobulin phase 20

21. IMMEDIATE SPIN PHASE Conducted at room temperature and is a check against errors in ABO typing. It detects ABO incompatibilites but insensitive to the presence of other RBC alloantibodies. Takes 1 to 5 minutes In emergency situations,this step may serve as a sole confirmatory process to eliminate reactions that may result from human errors in ABO-RH typing  21

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23. INCUBATION PHASE               Helps in detection of incomplete antibodies or antibodies able to attach to a specific antigen but are unable to cause agglutination in saline suspension of RBC.        Involves incubation of test tube  at 37c in albumin for 30 to 45 min or low ionic strength salt solution for 10 to 20 min.         RBCs are centrifused,resuspended and observed for hemolysis and agglutination          RBCs are then washed and resuspended in solution to remove unbound Igs . 23

24. INDIRECT ANTIGLOBULIN OR INDIRECT COOMBS PHASE          Antiglobulin sera is added to the test tubes          The antihuman antibodies present in the sera become attached to the antibody on the RBCs causing agglutination 24

25. ABO Incompatible Transfusion Reactions CAUSES  -Clerical errors: commonest cause          1.Misidentification of recipient –mostly occur in                                                emergencies,icu,operation theatres          2.Wrong samples/ blood packs   -Technical errors:           1.In grouping of patient or donor blood           2.In cross matching Mismatched blood transfusion leads to hemolytic transfusion reactions 25

26.             HEMOLYTIC TRANSFUSION REACTION Most severe type of transfusion reactions.categorized  into two types Acute or Intravascular HTR which is due to ABO incompatibility that lead to activation of complement cascade that destroy donor cells.         Delayed or extravascular HTR –Rh or minor group incompatibility       Extravascular RBC destruction is less serious than that of intravascular         26

27. ACUTE HEMOLYTIC TRANSFUSION REACTION   Acute intravascular hemolysis is usually due to ABO blood incompatibility,and the reported frequency is 1:38,000 transfusions . These reactions are often severe and may occur after infusion of little as 10-15 ml of ABO incompatible blood. The risk of fatal hemolytic reactions is about 1 in 100,000 transfusions                               27

28. CLINICAL FEATURES SYMPTOMS                                                   SIGNS       Chills                                                                Fever       Chest and flank pain                                     Rigors       Headache                                                       Flushing       Itching                                                             Restlessness       Palpitations                                                    Hypotension       Dyspnea                                                          Tachycardia       Nausea                                                            Utricaria       Vomiting                                                          Hemoglobinuria 28

29. Patients under general anesthesia early alarming signs may be unexplained tachycardia           Hemoglobinuria          Bleeding diathesis           Hypotension Consequences of intravascular hemolysis :           Acute renal failure          Disseminated intravascular coagulation Acute renal failure         Usually free hb circulates as complex with haptoglobulin  [bind approx 100mg of hb /100ml of plamsa ] which is cleared by RES         As little as 50ml of incompatible blood may exceed binding capacity of haptoglobulin          Plasma with 2mg/dl of hb -faintly pink or light brown                            100mg/dl of hb -red                             150mg/dl- hemoglobinuria occurs 29

30. Hb  gets precipitated to acid hematin in the distal tubule causing mechanical tubular blockage. DIC     Intravascular hemolysis  leads to release of procoagulant material from red cell stroma erythrocytin,which activates intrinsic system of coagulation and leads to fibrin formation.      Subsequently platelets, factor I,II,V and VII are consumed. I nvestigation – serum haptoglobulin , plasma and urine hemoglobulin,bilirubin and direct antiglobulin determinates 30

31. Treatment Stop the transfusion immediately Maintain the urine output at a minimum of 75-100ml/hr by the following methods:[since the magnitude of formation of precipitate is inversely related to ph and volume of urine flow ]          - Administer fluids intravenously and possibly mannitol       - Administer furosemide if intravenous fluids and mannitol are ineffective  . Alkalization of urine to prevent precipitation of acid hematin in the distal tubules. .Assay urine and plasma hemoglobin concentrations 31

32. Determine platelet count,prothrombin time,partial thromboplastin time amd serum fibrinogen level. Return unused blood to blood bank for repeat crossmatch. Send  patients  blood and urine sample to blood bank for cross examination. Prevent hypotension to ensure adequate renal blood flow.[hypotension may result from activation of kallikrein system] 32

33.      Delayed hemolytic tansfusion reaction Occurs mainly in recipients sensitized to RBC antigens by previous blood transfusions or pregnancy. Antibodies most commonly involved are those in Rh system. The concentration of antibody is so low that it cant be detected by tests before transfusion  RBC destruction occurs only when the level of antibody is increased after secondary stimulus[amnestic response] Occur days or weeks after blood transfusion  33

34. Jaundice and hemoglobinuria  can occur, can cause some impairment in renal function. Often manifested only by decrease in postransfusion hct . Suspected in any patient with unexplained decrease in hb 2 to 21 days after transfusion even without obvious manifestations of hemolysis . 34

35. 35 Management The treatment of delayed hemolytic reaction is primarily supportive. The frequency of delayed hemolytic reaction is approximately 1:12,000 transfusions . Although improved blood banking system, or procedures have decreased the incidence of immediate haemolytic reactions, the delayed haemolytic reactions are not preventable, because pretransfusion testing is unable to detect very low level of antibodies present in potential blood recipient’s.

36.       MASSIVE BLOOD TRANSFUSION transfusion of 10 or more units of packed red blood cells in a 24hrs period which almost replaces one blood volume based on the total blood volume of a 70 kg male Transfusion of >4units of prbc in one hour when on going need is there Replacement of 50% of total blood volume in within 3 hrs Transfusion of one unit blood within 5 minutes 36

37. In children - transfusion of >50% total blood volume in 3hr - Transfusion of >100% total blood volume in 24hr - Traansfusion support to replace on goning blood lossof >10% total blood volume per minute 37

38. Indications of massive blood transfusion Trauma Surgical procedures     Liver transplantation     Cardiothoracic and major vascular surgery      Major cancer and spine surgery Coagulation abnormalites       Acute traumatic coagulopathy       Clotting factor deficiencies       Dilutional coagulopathy 38

39. Obstetric diseases           Massive obstetrics hemorrhage includes fall in hb conc of >40g/dl or blood loss of >2500ml or transfusion of >4units RBC PPH means more than 1000ml blood loss from genital tract within 24hrs of birth           Common etiologies include uterine atony, plaxcenta previa,placenta acreta , placental abruption, uterine rupture,amniotic fluid embolism leading to DIC 39

40. MASSIVE TRANSFUSION PROTOCOL 40

41. Purpose of MTP To provide blood products early in the resuscitation and to treat coagulopathy in an immediate and sustained manner Hemostatic resuscitation can be achieved by providing predefined ratio of RBC:FFP:platelets of 1:1:1 Hemostatic  resuscitation has been reported to be beneficial in the trauma setting    41

42. Massive blood transfusion protocol are activated by clinician in response to massive bleeding. Generally this is activated after transfusion of 4-10 units. MTP have a pre-defined ratio of RBCs,FFP /Cryoprecipitate and platelet units (random donor platelets) in each pack {eg;1:1:1 or 2:1:1} for transfusion. Once the patient in this protocol,the blood bank ensures rapid and timely delivery of all the blood components together to facilitate resuscitation. This reduces the dependency on laboratory testing during the acute resuscitation phase. 42

43. Complications of massive blood transfusion 43

44. Coagulation abnormalites   1.Consumption coagulopathy mainly caused by dilution of coagulation factors by volume administration and duration of hypotension and hypoperfusion   -   Patients who have adequate perfusion and are not hypotensive for a long period tolerate administration of multiple units of blood without developing coagulopathy       Signs-oozing into surgical field,hematuria,gingival bleeding, petechiae,bleeding   from venipuncture sites,ecchymosis 44

45. Plasma undergoes progressive loss of coagulation factors during storage particularly factor v and VIII unless stored at -25c 2. Depletion of platelets platelet function is rapidly lost during storage of whole blood and virtually there is no platelet function after after 24hrs management- give platelet concentrates when patient shows signs of microvascular bleeding ,when platelet count falls below 50×10 9 /l consider platelet transfusion in cases when platelet count falls below 20 109/l even if there is no clinical evidence of bleeding because of risk of internal bleeding prophylactic use of platelet concentration patients receiving large volume blood transfusion is not recommended 45

46. 3.Microaggregates white cells and platelets can aggregate together in stored whole blood forming microaggregates during transfusion particularly a massive transfusion these microaggregates embolise to the lungs and results in development of ARDS Management- Filters can be used to remove microaggregates Use of buffy coat depleted packed red cells will decrease the likelihood of ARDS 46

47. 4.Disseminated intravascular coagulation It is abnormal activation of the coagulation and fibrinolytic systems resulting in consumption of coagulation factors and platelets. It is less likely due to transfusion itself than due to underlying reasons for transfusion such as hypovolemic shock,trauma,obstetric complications. Treatment should be directed at correcting the underlying cause 47

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49. citrate intoxication and hyperkalemia     -  Citrate binds to calcium and thus lowers the ionized plasma calcium conc     -  Leads to hypocalcemia ,dysrhythmia and hypotension  - however ionized calcium levels do not decrease enough to cause bleeding even with infusion of more than 1unit of blood every 10 minutes   - as citrate metabolism is mainly hepatic ,patient with hepatic dysfunction may demonstrate hypocalcemia and require calcium infusion during massive transfusion -treatment:1g calcium gluconate 10% given IV for every 5 units blood/FFP - Hyperkalemia       -  Even though serum k+ levels may be as high as 19 to 50meq/l in blood stored for 21days,the net gain of k+ is approx only 10meq/ l,when loss of k+ via blood loss is taken into account.       -  For clinically significant hyperkalemia to occur banked blood mut be given at a rate of 120ml/min or more    49

50. Hypothermia     Administration of blood that has been stored at 4c can decrease the recipient temperature Interfere with coagulation process by impairing coagulation factors and platelet functions If temperature decreases to <30c ,ventricular irritability and cardiac arrest may occur. Shivering from even mild hypothermia increases metabolic demands and is counterproductive to tissue perfusion Prevention-warming the blood to body temperature before transfusion 50

51. Acid base abnormalites     - Ph of storage media  is very acidic [ ph 5.5 for CPD]     - When this solution is added to unit of freshly drawn blood ph of blood immediately decreases from 7.4 to 7.1     -  Ph of banked blood continues to decrease to 6.9 after 21 days of storage as a result of accumulation of lactic and pyruvic acids by rbc metabolism and glycolysis       -Empirical administration of sodium bicarbonate is not indicated , administation should be guided by analysis of arterial blood gases     -  Blood transfusion provides citrate which can lead to endogenous generation of bicarbonate leading to metabolic alkalosis       51

52. TRALI Transfusion related acute lung injury presents as acute hypoxia and non cardiac pulmonary edema occurring within 6hours of blood product transfusion. No evidence of acute lung injury prior to transfusion Hypoxemia is defined as PaO2/FiO2 less than or equal to 300mm hg , oxygen saturation less than 90% on room air. Radiographic evidence of bilateral infiltrates without evidence of left atrial hypertension. 52

53. Symptoms-         fever,dyspnea ,fluid in ett , severe hypoxia are typical Management- stop blood transfusion, institute supportive measures supplemental o2 for mild cases Mechanical ventilation with low tidal volume and plateau pressure for moderate to severe cases IV corticosteroids to reduce complement mediated granulocyte activation  Blood bank should be notified to provide blood components from different donor and to quarantine all units from donor in question   All records should be reexamined and the results of patient HLA testing should be reevaluated if possible  Although most patients recover within 96hrs,TRALI remians the leading cause of transfusion related deaths 53

54. Transfusion associated circulatory overload      Excessive administration of blood volume leading to pulmonary edema with evidence for increased left sided cardiac filling pressures Elevated brain natriuretic peptide Elevated central venous pressure Evidence of left heart failure Acute respiratory distress. Raised JVP Widened pulmonary vascular pedicle on chest x ray. 54

55. Non hemolytic transfusion reactions    Febrile or allergic    Febrile reactions are most common    Caused by pyrogenic cytokines and intracellular contents release by donor leucocytes Symptoms- chills,fever,headache,myalgia , nausea and non productive cough,hypotension , chest pain, vomiting, dyspnea  Radiographic evidence of prehilar  nodule formation and lower lung infiltrates along with overt pulmonary edema   is seen  A direct antiglobulin test differentiates hemolytic reaction from febrile reaction as this test rules out attachment of antibody to transfused donor donor RBC  Use of leukoreduced  blood has lowered the incidence of febrile reactons 55

56. Allergic reactions-       Can be minor,anaphylactoid or anaphylactic. 1.  Most allergic reactions are minor and is Caused by the presence of foreign protein in transfused blood          - Most common symptom is utricaria associated with itching.ocasionally facial swelling         - Transfusion usually need not to be discontinued .anti histamines are used to relive the symptoms 2.Anaphylactoid are similar to anaphylaxis but are not mediated by IgE 3. Anaphylaxis is more severe form which is due to transfusion of IgA to patients who are IgA deficient  and has formed antiIgA         - Symptoms – dyspnea ,hypotension, laryngeal edema ,chest pain,shock       -  These patients should be given transfusion with washed RBC so that all traces of donor IgA have been removed or with blood that lacks IgA protein 56

57. Transfusion –Transmissible Infections Donor screening-attempts to reduce the ris of transfusion –transmissible diseases and to protect the donor from an adverse reaction due to donation High risk categories for potential transmission of a infectious agent : 1.significant travel histoy 2.history of injection drug use 3.Recent tattoos 4.men who have had sex with men in previous 12 months 57

58. Infectious disease testing for blood Discontinue serum alanine aminotransferase testing hepatitis c antibody testing antibody to hepatitis b core antigen HIV type1 HIV type 2 HIV antigen [p24] human t cell lymphotrophic virus type 1 and 2 serological tests for syphilis 58

59. Post Transfusion Hepatits 90% of posttransfusion hepatitis is caused by hepatitis C. It is also caused by hepatitis B and rarely D ,which are parenterally transmitted diseases. SIGNS AND SYMPTOMS Fatigue(67%) Hepatomegaly(67%) Chronic hepatitis(23%) Chronic active hepatitis(51%) Hepatocellular carcinoma(11%) 59

60. Management ANTIVIRAL THERAPHY MAVYRET( glecaprevir – pibrentavir ) HARVONI( ledipasvir – sofosbuvir ) EPCLUSA ( sofosbuvir – velpatasvir ) VOSEVI ( sofosbuvir – velpatasvir – voxilaprevir ) 60

61. Cytomegalovirus It is double stranded DNA virus belonging to herpiviridae family,acts as a normal flora in healthy adults. Infection with CMV virus is limited to human, transmitted through contact with body fluids of a previously infected individual survives best within the cells and persists in its latent form in the monocytes of people with antibody evidence of previous exposure infection 61

62. The recipients who are at high risk for CMV transmission are Pregnancy (multiple) Immaturity or immunosuppression (premature neonates) Allograft recipients Post splenectomy CMV causes a heterophile antibody negative response that closely resembles infectious mononucleosis in many respects. An infectious mononucleosis like syndrome that can occur 1 to 2 months after open heart surgery is known as post perfusion syndrome or post transfusion mononucleosis 62

63. Management To prevent this transmission in high risk populations Use of leukocyte reduced blood, use of frozen deglycerolized RBCs, screening for CMV antibody negative donors. 63

64. Zika virus Most recently, transfusion transmissible zika virus infection has been of concern. Transmitted by aedes mosquito ,its infection is associated with GBS,microcephaly in newborn whose mother were in infected during pregnancy. 80% of infected persons are asymptomatic that pose a potential threat to blood supply. PREVENTION; FDA issued guidance that all donations collected in the united states to be tested for zika virus using NAT. 64

65. Bacterial infections Bacterial contamination of blood products is the second leading cause of transfusion associated mortality. The prevalence of positive blood products ranges from 1:2000 for platelets to 1:7000 for PRBCs and may be due to inadequate antisepsis during phlebotomy. Both gram positive(staphylococcus) and gram negative(Yersinia and citrobacter ) bacteria can contaminate the blood transfusions and transmit the disease. PREVENTION: Blood products should be administered over a period shorter than 4hr to avoid the possibility of bacterial contamination. Syphilis,brucellosis,salmonellosis,yersiniosis and ricketsiosses are the specific bacterial disease rarely transmitted by blood transfusion from donors . 65

66. Parasitic infections Parasitic diseases that can be transmitted by transfusion include; Malaria Toxoplasmosis Chagas disease. 66

67. Other non infectious risk of blood transfusion MICROCHIMERISM: Chimerism refers to more than one cell line in an individual organisms. Significantly,donor lymphocytes may persists in a patient. The outcome of the patients with microchimerism is not known. POST TRANSFUSION PURPURA This refers to recipient alloantibodies attacking donor platelets antigen and is treated with intravenous immunoglobulin. HYPOTENSIVE TRANSFUSION REACTIONS; Activation of coagulation pathways activates production of bradykinin and allergic reactions. 67

68. REFERENCES Millers Anesthesia [ninth edition] Morgan and mikhails clinical anesthesiology -seventh edition 68

69. THANK YOU 69