Diagnosis & Management of Transfusion Reactions

1. Diagnosis & Management of Transfusion Reactions Christopher J. Gresens, M.D. VP & Medical Director, Clinical Services BloodSource

2. Outline • Brief Contextual Discussions • How We Manufacture Blood Components • Donor Blood Testing and the Transfusion Transmitted Diseases • Acute Transfusion Reactions • Delayed Transfusion Reactions • Evaluation/Management of Suspected Transfusion Reactions • Miscellaneous Transfusion Reactions • Q & A

3. How We Make Blood Components Collection Process • (1) Via Whole Blood Donation: Whole blood is collected from healthy blood donors into sterile blood bags that contain anticoagulant-preservative. • (2) Via Apheresis: Machines with internal centrifuges separate a donor’s blood into individual components (e.g., platelets, plasma, RBCs, etc.). The desired components are retained, while the remainder is returned to the donor.

4. Finger-stick capillary blood sampling Donor interview process

5. CuSO4 Hemoglobin determination Note: Other methods can also be used for this purpose.

6. BP, Pulse, and Temperature Check

7. The Collection Process Arm Disinfection Prior to Donation Phlebotomy (16 Gauge Needle)

8. The Collection Process Multi-bag whole blood collection kits Flow of whole blood into primary bag

9. Whole Blood Collection

10. Blood Component Manufacture fromWhole Blood (As Done in the USA) RBCs Centrifuge (low g forces) WHOLE BLOOD + Platelet-Rich Plasma

11. Centrifuge Used for Component Manufacture

12. Multi-pack Collection Bag

13. Centrifuge - Interior

15. Blood Component Manufacture from Whole Blood RBCs Centrifuge (higher g forces) Platelets + or Plasma Freeze • Leukoreduce • Possibly irradiate • Other + Platelet-Rich Plasma Fresh Frozen Plasma (FFP) or “Plasma Frozen with 24 hours”

16. Blood ComponentManufacture from Whole Blood • Thaw (4° C) • Centrifuge Fresh Frozen Plasma (FFP) Cryoprecipitate + Cryo-Reduced Plasma

17. Using the “Leftovers” Wisely Sent for further processing Plasma (of any kind) Plasma Derivatives • Albumin • Factor VIII • Immune globulin • etc.

18. Blood can be optimally utilized by the use of specifically required components instead of whole blood… RBC FFP PLT

19. “Shotgun” Approach vs. . . .

20. Component Therapy

21. The Principles of Apheresis Plasma Platelets Mononuclear Cells Granulocytes Red Blood Cells Whole Blood Whole Blood Anticoagulant added Remaining blood constituents returned (vein) (vein) Blood constituents separated by centrifuge and selectively collected

22. Caridian BCT Trima Accel

23. Haemonetics PCS-2

24. Plasma Collected Via Apheresis Typically200 mLto800 mL FFP Made from Apheresis

25. Donor sample tubes being readied for testing

26. InfectiousDisease testing (Abbott PRISM)

27. Chagas Disease Testing (Ortho Platform)

28. NAT – We recently converted to Chiron Ultrio (HIV, HBV, and HCV); we also do WNV by NAT

29. Olympus PK-7200 (ABO, Rh, syphilis)

30. CBC analysis by Pentra XL-80

31. Platelet Bacterial Detection QC Testing by BacT/ALERT

32. Donor Blood Testing • ABO • Rh • Antibody Screen • Infectious Diseases • Syphilis • HBsAg • Anti-HIV-1/2 • Anti-HBc

33. Donor Blood Testing • Infectious Diseases • Anti-HTLV-I/II • Anti-HCV • HIV Nucleic acid testing (NAT) • HCV NAT • WNV NAT • Anti-T.cruzi (Chagas disease) • (On some units) Anti-CMV

34. Transfusion Risks • HIV: 1 in 2,135,000 units • HBV: 1 in 205,000-to-488,000 units • HCV: 1 in 1,935,000 units • HTLV-I/II: 1 in 514,000-2,993,000 units • CMV: << 1: 100 (when leukoreduced or CMV-negative blood used) • WNV: ? (region-specific; very low) • vCJD: ? (risk very, very low—even in U.K.) Infectious Risks of Blood Transfusion. Blood Bulletin (America’s Blood Centers). December 2001.

35. Acute Transfusion Reactions

36. Case Study • 42-year-old male; S/P CABG surgery; group O • Transfused with 2 units RBCs postoperatively • Develops nausea, 1.5° C temperature elevation, hypotension, and red urine • Pre-transfusion DAT 0; post-transfusion DAT 4+ • Diagnosis and Management???

37. Acute Immune-Mediated Hemolytic Transfusion Reactions • Cause: Antigen-antibody reactions • Consequences: Shock, DIC, acute renal failure, and/or (sometimes) death • Presentation: Fever/chills, hypotension, nausea, chest/back/infusion site pain, flushing, dyspnea, hemoglobinuria, oliguria, anuria, shock, generalized bleeding • Pathophysiology: Complement, coagulation, and neuroendocrine system involvement • Therapy: Treat hypotension, renal, and other problems • Prevention: Vigilance

38. A Pictorial Representation of What Happens

39. Acute Non-Immune Hemolytic Transfusion Reactions • Examples: • Osmotic lysis • Accidental freezing • Accidental overheating • Inadequate deglycerolization • Mechanical hemolysis • Intrinsic defects in either donor’s or recipient’s RBCs (e.g., G-6PD deficiency, sickle cell disease)

40. Case Study • 7-year-old female with AML; post-chemotherapy; group A • Transfused ½ plateletpheresis unit (CMV-negative, irradiated, & leukoreduced) • 20 minutes into transfusion, developsnausea, 2.4° C temperature elevation, hypotension, and red urine • Diagnosis and Management???

41. Septic Transfusion Reactions • Presentation: High fever, shock, DIC, hemoglobinuria, renal failure, GI complications, generalized muscle pain • RBC Contaminants: Yersinia enterocolitica, Pseudomonas species, E. coli, etc. • Platelet Contaminants: Coagulase-negative Staphylococci, Salmonella, Staphylococcus aureus, etc. • Prevention: QC testing of all platelets, visual inspection of all blood products

42. After Before Bacteria from donor arm’s skinbefore and after cleansing

43. Case Study • 60-year-old male; GI bleeding; group AB • Transfused one unit RBCs • 2 minutes into transfusion, develops nausea, hypotension, and respiratory failure with wheezing (at first), followed by shallow, rapid breathing without wheezing • Diagnosis and Management???

44. Anaphylactic Transfusion Reactions • Cause: Reaction against IgA or otherplasma-soluble antigens in blood component • Presentation: (Absence of fever), respiratory andGI symptoms, shock, and/or syncope • Treatment: Give epinephrine, corticosteroids, etc.; maintain airway • Prevention: Transfuse with IgA-deficient (and/or carefully washed) products when necessary

45. Case Study • 22-year-old female; spontaneous bleedingand coagulopathy (cause unknown); group O • Transfused with 2 units of FFP • 2 minutes into transfusion, develops 1.4° C temperature elevation, hypotension, rapid respiratory compromise requiring intubation, foamy sputum, bilateral pulmonary edema on chest X-radiograph • Diagnosis and Management???

46. Transfusion-Related Acute Lung Injury (TRALI) • Causes • Major—Interaction between pre-existing (most often donor) HLA or granulocyte antibodies and WBCs of (usually) patient origin • Minor (?)—Neutrophil priming agent within donor blood that primes PMN oxidase in patient • Presentation: Acute respiratory insufficiency, fever, hypotension, CXR c/w pulmonary edema • Treatment: Respiratory support; ? corticosteroids

47. Pre-TRALI Chest X-Radiograph

48. Chest field consistent with TRALI

49. Currently Accepted Risks of Transfusion • Acute immune-mediated hemolytic transfusion reactions: 1 in 12,000 risk for ABO mismatched transfusion; 1 in 33,000 for major ABO mismatch; 1 in 600,000 for death(Linden et al. Transfusion 1992; 32: 601-606) • Anaphylactic transfusion reactions: 1 in 20,000 to 1:47,000(Salama A, et al. Transfusion 2004; 44: 509-511) • TRALI: 1in 300 to 1:5,000 (Kao S, et al. Transfusion 2003; 43: 185-191)

50. Febrile Non-Hemolytic Reactions • Presentation:  temperature > 1° C with no other explanations (sometimes with chills and rigors) • Causes • Reaction between recipient antibodies anddonor WBCs or … • Production of cytokines during product storage • Treatment: Give antipyretics & symptomatic relief • Prevention: Pre-storage leukoreduction of blood