Transfusion Reactions

1. Transfusion Reactions NICHOLAS TSU, M.D.

2. Objectives • Transfusion statistics and basics • Types • Diagnosis • Treatment

3. Transfusion Statistics • Transfusions in 2004 • 14.2 million units of packed red blood cells (PRBC’s) • 9.9 million units of platelets (84% apheresis units) • 4.1 million units of fresh-frozen plasma (FFP) • Approximately 40% of all transfused units administered by anesthesia personnel

4. Transfusion Risks • Infectious • Viral • Bacterial • Noninfectious • Reaction to RBC Antigens • Acute Hemolytic Transfusion Reactions (AHTR) • Delayed Hemolytic Transfusion Reactions (DHTR) • Reactions to Donor Proteins • Minor Allergic Reactions • Anaphylactic Reactions • White Cell-Related Transfusion Reactions • Febrile Reactions • Transfusion-Related Acute Lung Injury (TRALI)

5. Viral Infections

6. Bacterial Infections

7. Bacterial Infections • Incidence of sepsis much greater in platelets • Platelets stored at room temperature • Decreased risk with apheresis platelets • Most common organisms • Staphyloccos aureus • Klebsiella pneumoniae • Serratia marcescens • Staphyloccos epidermdidis • Yersinia enterocolitica

8. Bacterial Sources • Donor skin flora • Donor bacteremia • Contamination from • Collection • Processing • Storage

9. Signs and Symptoms of Bacterial Infection • Fevers • Chills • Tacycardia • Dyspnea • Emesis • Shock • DIC • Acute renal failure

10. Diagnosis and Treatment • Stop transfusion • Obtain blood cultures • Treat with broad spectrum antibiotics • Notify the blood bank immediately • Prevent other units from same donor being transfused

11. Acute Hemolytic Transfusion Reactions • Most hazardous against foreign RBC’s • Hemolysis of donor RBC’s can lead to ARF & DIC • Mortality rate is 2% • Leading cause is clerical error

12. Acute Hemolytic Transfusion Reactions • Over 300 antigens on human RBC’s • Most common antibodies that fix complement • A, B, Kell, Kidd, Duffy • Rh antibodies do not fix complement but can cause serious hemolysis

13. AHTR Pathophysiology • Antibodies and complement in recipient plasma attack antigens on donor RBC’s causing hemolysis • Antigen-antibody complexes activate Hageman factor (factor XII) producing bradykinin leading to capillary permeability and hypotension • Complement system releases histamine and serotonin from mast cells resulting in bronchospasm • 30-50% of patients will develop DIC

14. AHTR Pathophysiology • Hemolysis releases hemoglobin (Hb) • Hb binds to haptoglobin and albumin initially • Will circulate unbound until excreted by kidneys • Renal damage causes • Hypotension 2/2 systemic hypotension and renal vasoconstriction • Free Hb form acid hematin damaging renal tubules • Antigen-antibody complexes may deposit in glomeruli

15. Signs and Symptoms • Fever • Chills • Nausea and vomiting • Diarrhea • Rigors • Hypotension and tachycardia (bradykinin) • Flushed and dyspneic (histamine) • Chest and back pain (cytokine release) • Headache • Feeling of impending doom • Hemoglobinuria eventually oliguria

16. Diagnosis • Stop transfusion • Recheck patient and unit labeling • Examine centrifuged plasma sample for pinkish discoloration representing free Hb • Hemolysis should be assumed to be hemolytic transfusion reaction until proven otherwise • Notify blood bank • Aseptically seal unit and return • Coombs test • Examines recipient RBC’s for presence of surface immunoglobulins and complement

17. Treatment • Maintain systemic blood pressure • Deliver volume • Pressors • Inotropes • Preserve Renal function and urine output • Administering fluids • Diuretics (mannitol or furosemide) • Sodium bicarb to alkalinize urine • Prevent DIC • No specific therapy • Prevent hypotension and support cardiac output • Decreases stasis

18. Delayed Hemolytic Transfusion Reactions • Compatible RBC’s are rapidly eliminated within days • Typically due to donor RBC antigen to which recipient has been previously exposed via transfusion or pregnancy • Over time antibody levels fall too low to be detected • With re-exposure anamnestic response results in antibodies and lysis of foreign RBC’s • Coated RBC’s are sequestered extravascularly (spleen and reticuloendothelial system) and lysed

19. Diagnosis and Treatment • Usually detected in the first or second week • Low-grade fever • Increased indirect bilirubin • Unexplained reduction in Hb • Decreased serum haptoglobin • Confirmed by positive Coomb’s test • Resolves as transfused cells are removed • Monitor Hb • Maintain hydration • Re-transfuse if necessary

20. Minor Allergic Reactions • Allergic reactions to proteins in donor plasma cause urticarial reactions in 0.5 to 4% of all transfusions • Most frequent in FFP or platelets • Itching, swelling, rash • Treat with diphenhydramine

21. Anaphylactic Reactions • Seen typically in pt’s with hereditary IgA deficiency • Previously sensitized during pregnancy or exposed to blood with foreign IgA • Dyspnea, bronchospasm, angioedema, hypotension • Discontinue transfusion • Administer epinephrine and methylprednisolone

22. Febrile Reactions • Pt’s who receive multiple transfusions of RBC’s will develop human leukocyte antigens (HLA) • On subsequent RBC transfusions antibodies attack donor leukocytes causing febrile reactions • Occur in up to 2% of platelet, FFP, and RBC transfusions • Increase in temperature of more than 1 degree C with 4 hours of transfusion • Defervesces within 48 hours • Occasional chills, dyspnea, anxiety, headache, myalgia • Treat with acetaminophen • Differentiate with direct Coomb’s test

23. Transfusion-Related Acute Lung Injury • TRALI is a noncardiogenic form of pulmonary edema occurring after blood product administration • Associated with all plasma-containing components • Estimated at 1:1271 to 1:5000 transfusions • Mortality of at least 5%

24. Transfusion-Related Acute Lung Injury • Occurs when mediators present in the plasma of donor blood activates leukocytes in the host • Activated leukocytes are sequestered by the lungs • Leukocyte mediators are released and cause increased capillary permeability and endothelial damage • “two hit theory” • Trauma, surgery, sepsis may first “prime” native granulocytes causing surface adhesion sites resulting lung sequestration • Biologically active mediators that are breakdown products from cellular elements in blood products activate sequestered leukocytes

25. Signs and Symptoms • Within 6 hours of transfusion • Dspnea • Chills • Fever • Noncardiogenic pulmonary edema/bilateral pulmonary infiltrates • Hypotension/hypertension may occur

26. Diagnostic Criteria • Acute onset of hypoxemia (within 6 hours of conclusion of transfusion) • Bilateral CXR infiltrates consistent with ALI • Absence of evidence of left atrial hypertension • Absence of temporally related causes of ALI

27. Treatment • Largely supportive • Transfusion should be stopped if recognized in time • Supplemental oxygen and ventilation support provided if necessary • Use low tidal volume settings like in ARDS • No diuretics • Glucocorticoids have been administered but no evidence supporting their administration