Transfusion Medicine

Blood group : ABO system, Rh system and others
Pre-transfusion testing
Blood components : whole blood, packed red blood cells, platelets, fresh frozen plasma, cryoprecipitate, granulocyte, plasma derivatives and artificial blood
Complications of blood transfusion
Immune mediated reactions : acute hemolytic transfusion reaction, delayed hemolytic transfusion reaction, febrile nonhemolytic transfusion reaction, allergic reaction, graft vs host disease, TRALI- transfusion related acute lung injury, post transfusion purpura
Non immunological reactions : fluid overload, hypothermia, hyperkalemia, hypocalcemia, iron overload, immunomodulation
Infectious complication : bacterial, viral and others
National blood safety policy
Massive blood transfusion : definition, indications, protocol and mortality

1. Transfusion Medicine Dr Abdullah Ansari

2. Blood group system & Pre-transfusion testing

3. ABO blood group system 1 st system discovered in 1900 by Karl Landsteiner Gene on chromosome 9p and inherited in Mendelian co-dominant manner What is “Bombay ” blood group ??? Blood Group Antigen on RBC Antibody in plasma O None Anti A and Anti B A A Anti B B B Anti A AB A and B None

4. The Rh blood group system 2 nd most important system Gene on chromosome 1 The presence of D antigen confers Rh positivity 15% lack this antigen Exposure of Rh- recipients to Rh+ cells results in production of anti-D antibodies

5. Other blood group systems More than 100 systems recognised, composed of more than 500 antigens Clinically significant systems are Kelly, Kidd & Duffy system MNS system Lewis & P system I/ i system

6. Pre-tranfusion testing Two stages – “type & screen” Forward type Determine ABO & Rh phenotype of recipient RBC Antisera against A, B & D antigens used Reverse type Determine the antibodies: anti-A, anti-B & anti-D in patient’s serum Should correlate with ABO phenotype

7. Cont … Antibody screen Determine antibodies in patient’s serum directed against other RBC antigens Type O RBC (containing major antigens of most blood groups) is mixed with patient’s serum Cross-matching Performed after antibody screen, when the antibodies in patient’s serum are recognised Blood selected for cross matching should be ABO compatible and lack the antigens for which patient has antibodies

8. Bedside procedure for safe transfusion

9. Blood Components

10. Whole Blood 450 ml donor blood collected as “whole blood” into 63 ml CPDA-1 (citrate phosphate dextrose adenine) as anticoagulant preservative Hematocrit is 30-40% Stored at 4°C At this temperature, platelets lose viability, granulocytes disintegrate and labile coagulation factors decline Indication: acute hemorrhage with >25% blood loss Provide both oxygen carrying capacity & volume expansion

11. Blood component separation

12. Blood components

13. Packed red blood cells Volume is 180-200 ml Shelf life of 35 days at 4°C Hematocrit is 65-75% 1 unit PRBC raises Hb by 1 g/ dL or Hct by 3% Increases oxygen carrying capacity in anemic patients but without volume expansion Transfusion threshold is 7 g/dl in normovolumic patients without cardiac disease and comorbid conditions In critical patients, Hb target is 10 g/dl

14. Platelets Random Donor Platelets (RDP)/ pooled platelets : prepared from whole blood by centrifugation Single Donor Platelets (SDP)/ jumbo platelets : prepared by plasma apheresis machine Volume of RDP is 50-70 ml & SDP is 200-400 ml Shelf life of 5 days at 22°C

15. Platelets cont … 1 unit of SDP = 6 units of RDP 1 RDP increases platelet count by 5000-10000 , in unsensitised patient without increased platelet consumption (DIC, splenomegaly, fever) Threshold for prophylactic platelet transfusion is 10000 If patient is without fever or infection ( eg ITP), a threshold of 5000 is sufficient For invasive procedures & surgeries, platelet target is 50000

16. Fresh frozen plasma FFP contains coagulation factors & plasma proteins - albumin, fibrinogen, anti-thrombin , protein C & S Volume is 200-250 ml Shelf life of >1 year at - 30°C , if thawed can be stored for 24 hr at 4°C Indications are coagulation disorders like DIC, liver diseases, congenital bleeding disorders & reversal of warfarin therapy Doze is 10-15 ml/kg body weight 1 unit FFP raises coagulation factors by 2% Transfusion monitored by PT/INR , stopped when INR <1.5

17. Cryoprecipitate It contains fibrinogen, factor VIII & von Willebrand factor 1 unit cryoprecipitate contains 80 units of factor VIII Volume is 10-15 ml Shelf life of >1 year at -30°C Indications are DIC ( serum fibrinogen < 100mg/dl ), hemophilia A (poor countries) and von Willebrand disease

18. Granulocytes Harvested from donors by apheresis after stimulation by G-CSF & dexamethasone Indicated in febrile neutropenia (ANC<500)

19. Plasma derivatives Specific protein concentrates including albumin, intravenous immunoglobulin, anti-thrombin , and coagulation factors Hyperimmune globulins such as anti-D, and antisera to hepatitis B virus (HBV ), varicella-zoster virus, CMV & other infectious agents

20. Artificial Blood Two main categories of oxygen carrying blood substitutes Hemoglobin based oxygen carriers Perfluorocarbon based oxygen carriers In trial stage

21. Complications of Blood Transfusion

22. Adverse reactions to blood transfusion Immune-mediated reactions are due to preformed donor or recipient antibody , however cellular components of stored blood may also cause immune reactions Non-immune reactions are due to the chemical and physical properties of stored blood components and its additives like anticoagulant. It include infections complications

23. Risk of transfusion complications

24. IMMUNE-MEDIATED REACTIONS

25. Acute Hemolytic Transfusion Reactions Mechanism: The recipient has preformed antibodies that lyse donor RBC The ABO alloantibodies are responsible for the majority , however , alloantibodies against other RBC antigens, Rh , Kell , and Duffy are associated with more fatal reactions Presentation: H ypotension , tachypnea, tachycardia, fever, chills , hemoglobinuria , chest pain , flank pain, and discomfort at the infusion site

26. AHTR Cont... Management: When suspected, stop transfusion immediately. Direct Coombs test detects the antibody bound to RBC Hemolysis studies including serum haptoglobin , lactate dehydrogenase, and indirect bilirubin levels Hemolysis causes renal dysfunction . Give intravenous fluids to induce diuresis Tissue factor released from lysed erythrocytes may initiate D IC. Coagulation studies including PT, aPTT , fibrinogen, and platelet count

27. Delayed Hemolytic Transfusion Reactions Mechanism: These patients are previously sensitized to RBC antigens , but have low antibody levels and negative antibody screen. When re-transfused with the same antigen , memory response results in early production of antibody ( 1–2 weeks after transfusion ) The transfused, antibody-coated RBC are removed by the reticuloendothelial system Presentation: Mild reaction Management: No specific therapy is usually required

28. Febrile Non-hemolytic Transfusion Reaction The most frequent blood transfusion reaction Mechanism: Antibodies directed against donor WBC , and Cytokines released from cells within stored blood components Presentation : F ever with chills and rigors Management: Use leukocyte-reduced blood products

29. Allergic Reactions Mechanism: A llergy to plasma proteins in transfused component s Presentation: Urticaria , pruritus, anaphylaxis Management: S top transfusion temporarily and administer antihistamines , corticosteroids if severe. Prevention: Cellular components washing to remove residual plasma

30. Graft-Versus-Host Disease Mechanism: Donor T lymphocytes recognize recipient's HLA antigens as foreign and mount an immune response Presentation: F ever , cutaneous eruption, diarrhea, and liver function abnormalities Management: Resistant to immunosuppressive therapies . Clinical manifestations appear at 8–10 days, and death occurs at 3–4 weeks Prevention: I rradiation of cellular components before transfusion

31. Transfusion-related acute lung injury (TRALI) TRALI is the most common cause of transfusion related fatalities Definition: TRALI is defined as an acute lung injury (PaO 2 /FiO 2  <300 mmHg) that is temporally related to a blood transfusion ; specifically, it occurs within the first six hours following a transfusion Mechanism: The donor anti-HLA class II antibodies bind recipient neutrophils , these neutrophils aggregate in pulmonary vasculature and release inflammatory mediators that increase capillary permeability

32. TRALI Cont... Risk factors: S moking , chronic alcohol use, shock, liver surgery, mechanical ventilation and positive fluid balance Presentation: Symptoms of hypoxia ( PaO 2 /FiO 2  <300 mmHg ) and signs of non-cardiogenic pulmonary edema, including bilateral interstitial infiltrates on chest x-ray Management: Supportive

33. Chest X-ray of TRALI... Bilateral interstitial infiltrates

34. Post - transfusion Purpura Mechanism: Anti-platelet antibodies are produced that react to both donor and recipient platelets Presentation: D elayed thrombocytopenia 7–10 days after platelet transfusion Management : I ntravenous immunoglobulin to neutralize the antibodies , or plasma exchange to remove the antibodies

35. NON - IMMUNOLOGIC REACTIONS

36. Fluid Overload Blood components are excellent volume expanders, and transfusion may quickly lead to transfusion-associated circulatory overload (TACO) Dyspnea with SpaO 2 < 90%, bilateral infiltrates on chest x-ray, and systolic hypertension are found with TACO Monitoring the rate and volume of transfusion and using a diuretic can minimize this problem

37. Hypothermia Refrigerated (4°C) or frozen (−18°C or below) blood components when rapidly infused Cardiac dysrhythmias on exposure of the SA node to cold fluid A n in-line warmer will prevent this complication

38. Electrolyte Toxicity Hyperkalemia : RBC leakage during storage increases the potassium concentration in blood unit Prevented by using fresh or washed RBCs in high risk patients like renal failure Hypocalcemia : Citrate , used as anticoagulant , chelates calcium and inhibits coagulation Hypocalcemia manifest by circumoral numbness and tingling sensation of fingers and toes

39. Iron Overload Each unit of RBCs contains 200–250 mg of iron Symptoms and signs appears after 100 units of RBC transfusion ( total-body iron load of 20 g ) Prevent by using alternative therapies ( eg erythropoietin in CKD ) and judicious transfusion Chelating agents, such as deferoxamine and deferasirox , used but response is often suboptimal

40. Immunomodulation Transfusion of allogeneic blood is immunosuppressive. Transfusion-related immunomodulation is thought to be mediated by transfused leukocytes. Leukocyte-depleted cellular products may cause less immunosuppression

41. INFECTIOUS COMPLICATIONS

42. National blood safety policy Testing for every unit of blood is mandatory for HIV Hepatitis B Hepatitis C Malaria Syphilis

43. Viral contamination Hepatitis C (HC V ) : a ntibodies to HCV and HCV RNA. Human immunodefi c ien c y virus ( HIV ) : antibodies to HIV, p24 antigen and HIV RNA Hepatitis B (HB V ) : HbsAg antigen Other Hepatitis viruses West N ile virus Cytomegalovirus (CMV) Human T lymp h otropi c virus (H TLV ) t ype 1 Parvovirus B19

44. Bacterial Contamination Most bacteria don’t grow well at cold temperatures, hence not common with PRBC and FFP. However, some gram-negative bacteria can grow at 1–6°C , eg Yersinia, Pseudomonas , Serratia , Acinetobacter and Escherichia species Platelet , stored at room temperature are more likely to contain skin contaminants eg c oagulase -negative staphylococci Presentation: Fever and chills, which can progress to septic shock and DIC Treatment: stop transfusion immediately if suspected, manage shock and give broad-spectrum antibiotics Sent blood component bag for culture and Gram stain

45. Other Infectious Agents Various parasites, including those causing malaria, babesiosis, and Chagas’ disease and syphilis can be transmitted by blood transfusion

46. Massive Blood Transfusion

47. Massive Blood Transfusion  Definition T he replacement of  one  blood  volume (equivalent to 10 units  o f blood) in any 24 hour period,  o r   Half of the blood volume (5 units of blood) in four hour  period in an adult

48. Massive transfusion indications Severe trauma Ruptured aortic aneurysm Vascular/aortic surger ies Obstetric complications

49. Massive Transfusion  Protocol    Th es e parameters should be measured frequently (every 30‐60 minutes,  or after transfusion of  blood component).   Temperature Acid‐base  status Ionised   calcium  ( Ca ) Haemoglobin   Platelets  ( Plt ) PT/APTT  (activated  partial  thromboplastin   time) F ibrinogen

50. Mortality Mortality  is high in massive transfusion Its etiology includes  hypotension,  acidosis ,  coagulopathy, shock and underlying condition  of the patient The lethal  triad of acidosis ,  hypothermia and  coagulopathy   have the highest mortality rate It  is often   the underlying  cause   and   consequences   of major hemorrhage   that result in  complications , rather  than   the transfusion  itself