TRALI due to granulocyte-agglutinating human neutrophil antigen-3a (5b) alloantibodies in donor plasma: a report of 2 fatalities

BACKGROUND : TRALI is usually an immunologic reaction to WBC antibodies in infused plasma and ranks second only to ABO mismatch as a cause of transfusion‐associated death. Implicated donors are usually multiparous women (≥3 pregnancies). STUDY DESIGN AND METHODS : Two fatal cases of TRALI were evaluated by reviewing clinical and laboratory findings and characterizing alloantibodies present in donor plasma. Investigation for WBC antibodies was by lymphocytotoxicity (LCT), FlowPRA (FlowPRA, One Lambda, Inc.) and granulocyte immunofluorescence and agglutination assays. Patient 1 was a 62‐year‐old man with chronic T‐cell lymphocytic leukemia, and Patient 2 was a 54‐year‐old woman undergoing a cadaveric kidney transplant. Both patients developed acute respiratory distress and hypotension during (Patient 1) and approximately 30 minutes after (Patient 2) transfusion. Fulminant pulmonary edema ensued in both cases necessitating mechanical ventilation and both patients died within 24 hours of the onset of respiratory complications. RESULTS : The donors of the implicated blood components were women with a history of two pregnancies but no blood transfusions. Weak apparently panreactive granulocyte antibodies were detected with flow cytometry. However, in the granulocyte agglutination test, strong antibodies specific for human neutrophil antigen (HNA)‐3a (5b) were identified in both donors. CONCLUSION : It is concluded that female blood donors with only two previous pregnancies can form clinically important granulocyte‐reactive alloantibodies leading to fatal TRALI reactions in recipients. The sometimes devastating consequences of TRALI should prompt the development of strategies to prevent or reduce its incidence. Further research is warranted to investigate recipient and donor factors responsible for TRALI, including whether 5b (HNA‐3a) alloantibodies are especially prone to cause severe reactions, and to better characterize the HNA‐3a (5b) antigen, particularly at the molecular level.