A febrile transfusion reaction during transfusion is most commonly due to antibodies against which donor component?

• A. Bacterial contamination
• B. Recipient anti-HLA antibodies against donor leukocytes
• C. ABO incompatibility
• D. Anaphylaxis

Answer: (C)

Febrile transfusion reactions are most often immune-mediated by the recipient’s antibodies against donor leukocytes. The key target is HLA antigens on donor white blood cells. When a patient has preformed anti-HLA antibodies and is exposed to donor leukocytes in a transfused unit, this triggers an immune reaction with release of cytokines, leading to fever and chills during the transfusion. This is the classic mechanism behind febrile nonhemolytic transfusion reactions.

ABO incompatibility can cause fever as part of an acute hemolytic reaction, but that scenario is less common due to strict pretransfusion testing and presents with more severe signs of hemolysis. Bacterial contamination is another cause of fever during transfusion but arises from infection rather than an antibody-mediated leukocyte reaction. Anaphylaxis, on the other hand, is a nonfever, IgA-related or other nonimmune-mediated reaction and has a different presentation.