Why can a transfusion reaction cause fever?

A febrile reaction following a blood transfusion is primarily caused by the recipient's immune system reacting to donor leukocytes (white blood cells).1

Patients who have received multiple transfusions may develop antibodies specifically targeting these donor leukocytes. When these antibodies encounter the donor cells during a subsequent transfusion, they trigger a brisk immune response that manifests as a fever. This type of complication can be prevented by using leukoreduced blood components, which have had the white blood cells removed prior to administration.1