1. Transfusion Medicine Cheryl Pollock 13 November 03

2. Objectives An understanding of: An understanding of: –Available blood products –Appropriate selection of blood products according to the clinical setting –Potential complications of the transfusion

3. Outline Blood banking Blood banking Emergency transfusions Emergency transfusions Transfusion reactions and risks Transfusion reactions and risks Component therapy Component therapy

4. Blood Bank Basics Type & screen Type & screen –Blood group (ABO) identification –Rh typing –Antibody screening Cross-matching Cross-matching

5. ABO Identification >400 RBC antigens have been identified >400 RBC antigens have been identified –Major ones are ABO type, and Rh type Anti-ABO Abs are IgM that bind complement and cause agglutination and destruction of red cells => acute intravascular hemolysis Anti-ABO Abs are IgM that bind complement and cause agglutination and destruction of red cells => acute intravascular hemolysis Presence of A&B antigens are determined by testing with anti-A and anti-B Abs Presence of A&B antigens are determined by testing with anti-A and anti-B Abs

6. ABO Compatibility Phenotype RBC Ag Serum Ab Can receive A A anti-B anti-B A, O A, O B B anti-A anti-A B, O B, O AB AB A and B A and B None None A, B, O A, B, O O None Noneanti-A,anti-B O

7. Rh Typing Major Rh system Ag is the ‘D’ Ag Major Rh system Ag is the ‘D’ Ag Rh status determined by testing with anti- D antibodies Rh status determined by testing with anti- D antibodies Rh-neg females of child-bearing age always get Rh neg blood products Rh-neg females of child-bearing age always get Rh neg blood products Rh-neg males and elderly females can get Rh-pos blood if emergent transfusion required Rh-neg males and elderly females can get Rh-pos blood if emergent transfusion required

8. Antibody Screening To determine presence of: To determine presence of: Complete (agglutinating) antibodies Complete (agglutinating) antibodies –Agglutinate RBCs in saline –Usually IgM –Responsible for HTR Incomplete (non-agglutinating) antibodies Incomplete (non-agglutinating) antibodies –special techniques to visualize agglutination –Usually IgG –Not responsible for HTR

9. Antibody Screening All antibody screens are negative All antibody screens are negative –Patient has no unexpected anti-bodies –Donor blood released after an abbreviated or electronic cross-match Any antibody screens are positive Any antibody screens are positive –Patient has one/more unexpected antibodies which need identification –Donors must be antigen-negative –Full cross-match required

10. Antibody Screening: Coombs Test Direct Coombs: Direct Coombs: –To detect Abs or complement on surface Ags of RBCs –Agglutination= IgG antibodies in the patient’s serum have bound to recipient RBCs –Indications:  Hemolytic disease of newborn  Hemolytic anemia  Hemolytic transfusion reaction

11. Antibody Screening: Coombs Test Indirect Coombs Indirect Coombs –Indirect antiglobulin test –Detect Abs in serum that can recognize Ags on RBC. –i.e. detect Abs capable of hemolysing RBCs –By mixing serum with donor RBC and then anti-antibody Abs: RBC agglutination = +test –Indications:  Cross-matching -bl gr Abs in pregnant pts  Atypical bl gr

12. Pre-transfusion Testing Donor Donor –ABO and Rh status confirmed Recipient Recipient –Abo and Rh determined –Antibody screening  For 18 clinically-relevant antigens  Indirect Coombs  If positive: specific identification, transfusion ideally delayed

13. Cross-Matching Test of donor/recipient RBC compatibility Test of donor/recipient RBC compatibility Immediate “spin” cross-match Immediate “spin” cross-match –Recipient serum + donor RBCs, spin tube, read immediately –Detects ABO incompatibility only Complete cross-match Complete cross-match –If antibody screen + –Donor units w/out specific Ag are each tested with indirect Coombs

14. Cross-Matching Electronic cross-match Electronic cross-match –Donor blood issued based on blood bank info –Recipient’s ABO and Rh type has been done twice and filed in computer –No clinically significant antibodies found in current or past blood samples –Contraindications:  Significant antibodies present (current or past)

15. Emergency Transfusions PRBCs are the only blood product that can be used for emergency transfusion PRBCs are the only blood product that can be used for emergency transfusion Plasma products contain too many Abs Plasma products contain too many Abs Patient stability and the time available before intervention is needed will determine what is chosen Patient stability and the time available before intervention is needed will determine what is chosen Prior to transfusion, draw blood for typing and cross-matching Prior to transfusion, draw blood for typing and cross-matching

16. Indications for ED Transfusion Consider Consider –Comorbidity-Cardiac status –Rate of bleeding Acute/subacute bleed with impaired oxygen delivery to tissues Acute/subacute bleed with impaired oxygen delivery to tissues Hb <60-70 g/L Hb <60-70 g/L Symptomatic chronic anemia with Hb <60- 70 g/L Symptomatic chronic anemia with Hb <60- 70 g/L Pre-op Pre-op

17. Pediatric Pearls Hemodynamic parameters can be deceiving Hemodynamic parameters can be deceiving Normotensive until ~30% blood volume lost acutely Normotensive until ~30% blood volume lost acutely In pediatric trauma, emergency transfusion of >20 ml/kg is associated with increased mortality In pediatric trauma, emergency transfusion of >20 ml/kg is associated with increased mortality

18. Emergency transfusions Case 1 Case 1 56 y.o. male, motorcycle vs. car, with open femur fracture, unstable pelvis 56 y.o. male, motorcycle vs. car, with open femur fracture, unstable pelvis HR 130, bp 80/50, intubated at scene for GCS=6. HR 130, bp 80/50, intubated at scene for GCS=6. Blood? How soon? Blood? How soon?

19. Emergency Transfusions Universal Donor Group O Universal Donor Group O –Uncross-matched type O+ –Indications  Massive, uncontrolled hemorrhage from any cause  e.g. trauma, massive GI bleed, ruptured AAA –Women of child-bearing age need group O-

20. Emergency Transfusions: Other Options Type-Specific: Type-Specific: –5-10 min –ABO grouping, Rh typing – pt can be initially stabilized with crystalloid Incomplete cross-match Incomplete cross-match –30 min –ABO group, Rh type, “spin” cross-match Fully cross-match Fully cross-match –45-60 min –Reserved for specific patient for 48h

21. Administration PRBCs PRBCs –1 unit= 250ml, Hct= 60-70% –1 unit= 10 g/L increase in Hb –Peds: 1ml/kg PRBCs = 1% increase in hematocrit Bedside check Bedside check –Recipient & unit i.d., compatibility, expiration Large-bore needles to prevent hemolysis Large-bore needles to prevent hemolysis Blood warmers if massive transfusion Blood warmers if massive transfusion Blood only mixed with NS; no meds in same IV line Blood only mixed with NS; no meds in same IV line

22. Complications Transfusion reaction Transfusion reaction –Immediate –Delayed Infectious disease transmission Infectious disease transmission Transfusion-associated coagulopathies Transfusion-associated coagulopathies

23. Transfusion Reactions Immediate Immediate –Hemolytic  Intravascular –Non-hemolytic  Febrile  Allergic  Acute lung injury  Hypervolemia Delayed Delayed –Hemolytic (extravascular) –Infectious –Graft v. Host disease –Electrolyte imbalance

24. Transfusion Reactions Case 2 Case 2 70 y.o. male transfused for UGI bleed 70 y.o. male transfused for UGI bleed Transfusion of first unit PRBCs Transfusion of first unit PRBCs Acutely dyspneic, chest and low back pain, with burning at IV site. Acutely dyspneic, chest and low back pain, with burning at IV site. O/E: T 39C; HR 120; BP 100/60 O/E: T 39C; HR 120; BP 100/60

25. Acute Hemolytic Transfusion Reaction (Intravascular) Medical emergency due to ABO incompatibility (usually clerical error) Medical emergency due to ABO incompatibility (usually clerical error) Incompatible donor cells are destroyed by recipient antibodies Incompatible donor cells are destroyed by recipient antibodies Intravascular cell lysis=> hemoglobinemia and hemoglobinuria Intravascular cell lysis=> hemoglobinemia and hemoglobinuria Incidence ~1/20 000 transfusions Incidence ~1/20 000 transfusions Fatal 1/100 000 transfusions Fatal 1/100 000 transfusions

26. Acute Hemolytic Transfusion Reaction Presentation Presentation –chills, headache, N/V, burning at infusion site, –Chest tightness, dyspnea, low back pain –O/E: fever, tachycardia, hypotension Complications Complications –Cardiogenic shock, respiratory failure –ATN –DIC

27. Acute Hemolytic Reaction: Treatment Principles Prevention Prevention –Slow infusion for 15 min, Q5min VS STOP THE TRANSFUSION STOP THE TRANSFUSION –Replace IV tubing ABCs ABCs –Hemodynamic stability: crystalloid+/- pressors Adequate renal blood flow Adequate renal blood flow –Low-dose dopamine infusion –Urine output >100ml/h (fluid + furosemide)

28. Acute Hemolytic Reaction Evaluation Evaluation –Retype and cross-match –Direct & indirect Coombs –CBC, creatinine, PT/PTT –Haptoglobin, indirect BR, LDH, plasma free Hb –Urine for Hb

29. Immediate Transfusion Reactions Non-hemolytic Non-hemolytic –Febrile –Allergic –Acute lung injury –hypervolemia

30. Transfusion Reactions Case 3 Case 3 58 y.o. female post-elective TAH. 58 y.o. female post-elective TAH. During transfusion of 1 st unit PRBCs, c/o malaise, chills, ‘feels warm’. During transfusion of 1 st unit PRBCs, c/o malaise, chills, ‘feels warm’. O/E: T 39C; HR 90; BP 120/80 O/E: T 39C; HR 90; BP 120/80

31. Immediate Transfusion Reactions Febrile non-hemolytic Febrile non-hemolytic –Impossible to clinically distinguish from acute hemolytic reaction –Caused by Ag-Ab reaction involving plasma/components passively transfused –Usually mild –Worse if poor CV status, critically ill –Multi-transfused, multiparous patients

32. Febrile Non-hemolytic Reaction Presentation Presentation –Fever, chills Mgmt Mgmt –Stop transfusion; –Initial Rx as per acute hemolytic reaction –Acetaminophen, meperidine Evaluation Evaluation –Hemolytic W/U +/- infectious W/U

33. Allergic Transfusion Reaction Anaphylaxis Anaphylaxis –Rare (1/20 000 transfusions) –Suggests IgA deficiency –Presentation  Dyspnea, bronchospasm, shock –Mgmt  Epi, steroid, anti-histamine, pressors  Do not restart transfusion  Hemolytic W/U

34. Allergic Transfusion Reaction Minor Minor –Presentation  Urticaria, pruritis, erythema –Mgmt  Stop transfusion  Anti-histamine  If symptoms resolve, can restart transfusion  No further W/U

35. Transfusion-Related Acute Lung Injury Anti-WBC donor Abs + recipient WBC -> complement activation in lung -> non- cardiogenic pulmonary edema Anti-WBC donor Abs + recipient WBC -> complement activation in lung -> non- cardiogenic pulmonary edema Clinical diagnosis Clinical diagnosis Empiric treatment with steroids and respiratory support Empiric treatment with steroids and respiratory support Usually resolves within 48-96h Usually resolves within 48-96h

36. Delayed Transfusion Reactions Extravascular hemolytic transfusion reaction Extravascular hemolytic transfusion reaction –Days to weeks –Non-ABO Abs bind to RBCs -> deformation -> splenic sequestration -> extravascular hemolysis –Presentation  Mild reaction  Fever, jaundice; hemoglobinuria rare –No specific treatment

37. Delayed Transfusion Reactions All blood tested for: All blood tested for: –HIV Ag -HTLV I,II -HBsAg -syphilis –Ab to HIVI, II -HCV -HCAg Infectious Infectious –Hep A 1: 1 000 000 –Hep B 1: 30 000- 1: 250 000 –Hep C 1: 30 000 – 1: 150 000 –HIV 1: 200 000 – 1: 2 000 000 Data from Goodnough et al. NEJM 340:440, 1999

38. Delayed Transfusion Reactions Case 4 Case 4 44 y.o. male with Non-Hodgkin’s lymphoma 1/52 post-chemo 44 y.o. male with Non-Hodgkin’s lymphoma 1/52 post-chemo c/o fatigue, presyncope, SOBOE c/o fatigue, presyncope, SOBOE Hb 68 Hb 68 Risks of transfusion…. Risks of transfusion….

39. Graft v. Host Disease Rarely encountered in ED Rarely encountered in ED Keep in mind if considering transfusion in anemic leukemic/lymphoma pts Keep in mind if considering transfusion in anemic leukemic/lymphoma pts Viable lymphocytes transfused with PRBCs Viable lymphocytes transfused with PRBCs Multiplying, histoincompatible lymphocytes attack recipient->more BM suppression Multiplying, histoincompatible lymphocytes attack recipient->more BM suppression

40. Graft v. Host Disease Sx Sx –Fever, N/V, rash, diarrhea, hepatomegaly –Increased LFTs, pancytopenia No effective treatment No effective treatment Fatal Fatal Prevention Prevention –Gamma irradiation of all cell components, rendering donor lymphocytes incapable of proliferating

41. Delayed Transfusion Reactions Electrolyte imbalance Electrolyte imbalance –Hypocalcemia  Citrate preservative. –Hyperkalemia  K+ leakage across membrane  Problem in renal failure, neonates

42. Dilutional Coagulopathy Massive transfusion Massive transfusion Dilution of platelets & coagulation factors Dilution of platelets & coagulation factors Check platelets & coags after 5-10u PRBC Check platelets & coags after 5-10u PRBC Platelet transfusion only if thrombocytopenia+microvascular bleeding Platelet transfusion only if thrombocytopenia+microvascular bleeding FFP only if PT/PTT >1.5x norm FFP only if PT/PTT >1.5x norm

43. Component Therapy Platelets Platelets FFP FFP Cryoprecipitate Cryoprecipitate

44. Platelet Transfusion Indications Indications – count < 20 x 10 9 /L; < 50 x 10 9 /L if bleeding or planned invasive procedure Therapy Therapy –Should be ABO-specific –Usually 6u at a time: increase of 50-60 x10 9 /L –BUT…consider cause of thrombocytopenia  DIC, splenomegaly, antibodies may be refractory to platelet transfusion

45. Fresh Frozen Plasma All coagulation factors + fibrinogen All coagulation factors + fibrinogen Indications Indications –Emergent reversal of warfarin therapy –Correction of coagulation deficiencies Therapy Therapy –Must be ABO compatible –1u = ~250ml –Dose 10-15 ml/kg

46. Cryoprecipitate Contains Contains –Factor VIIIC, vonWillebrand Factor, fibrinogen Indications Indications –Bleeding associated with:  Hypo-/dysfibrinogenemia (e.g. DIC)  vonWillebrand’s disease if FVIII not available  Hemophilia A if FVIII not available Therapy Therapy –Should be ABO compatible (no cross-match) –Usual dose ~ 10u

47. References Marx: Rosen’s Emergency Medicine: concepts and Clinical Practice, 5 th ed. Marx: Rosen’s Emergency Medicine: concepts and Clinical Practice, 5 th ed. Tintinalli. Emergency Medicine: A Comprehensive Study Guide, 5 th ed. Tintinalli. Emergency Medicine: A Comprehensive Study Guide, 5 th ed. Ross, AK. Pediatric trauma. Anesthesia management. Anesthesiol Clin North Amer. 01 June 2001; 19(2): 309-37 Ross, AK. Pediatric trauma. Anesthesia management. Anesthesiol Clin North Amer. 01 June 2001; 19(2): 309-37