Patients receiving red blood cell (RBC) transfusions are at risk of developing alloantibodies against donor RBC antigens. The risk of alloimmunization is dependent on the number of units administered and patient's genetic predisposition, but has also been suggested to be modulated by a patient's clinical profile. Our aim was to examine whether immunosuppressants suppress the development of clinically relevant RBC antibodies.

A two‐center case‐referent study was performed where case patients and control patients were sampled from all consecutive patients (17,750 patients) who had received their first and subsequent RBC transfusions in a 5‐year period in the study centers. Cases were all patients with a first detected RBC alloantibody preceded by negative antibody screens. Control patients were two‐to‐one matched to the case patients on the number of RBC transfusions. Logistic regression analysis was used to examine the association between immunosuppressant exposure and the subsequent occurrence of RBC alloimmunization.

A total of 156 case patients and 312 control patients in the study received a median of six transfusions (interquartile range, 3‐11). Among the total study population, 207 patients received immunosuppressive therapy, with 142 patients receiving only corticosteroids, four receiving only other immunosuppressants, and 61 receiving both. The incidence of alloimmunization among patients using immunosuppressants was lower than among other patients receiving RBCs (adjusted relative rate, 0.55; 95% confidence interval, 0.34‐0.91).

Our findings support a considerably lower risk of alloimmunization with the use of immunosuppressive medications.