Strategies to mitigate transfusion‐associated red blood cell alloimmunization in sickle cell disease: A retrospective analysis

Abstract Background The American Society of Hematology (ASH) recommends prophylactic limited red blood cell (RBC) antigen matching for C, E, and K for patients with sickle cell disease (SCD). At our institution, reflexive extended antigen matching is employed: no antigen matching is undertaken initially; in the event of RBC alloimmunization, extended antigen matching (C/c, E/e, K, Fy a /Fy b , Jk a /Jk b , S/s) is performed prospectively. Study Design and Methods We compared alloimmunization rates and costs of reflexive extended antigen matching with other RBC antigen‐matching strategies. A 5‐year retrospective review was conducted of all patients with SCD, who were transfused during the study period and lacked prior immunization. Age, sex, ABO/Rh type, number of transfused units of RBCs, antibody history, and transfusion reactions were assessed. The alloimmunization rate was defined as the number of new alloantibodies per 100 units of transfused RBCs. Costs were estimated for reflexive extended antigen matching, limited antigen matching, and extended antigen matching. Results Of 805 patients, 325 (40.4%) met inclusion criteria. Fifty (50/325, 15.4%) patients developed a positive antibody‐detection test after transfusing a median of 9 (interquartile range: 3–14) units (alloimmunization rate 0.29 per 100 RBCs); anti‐C, E, and K were leading alloantibodies. Seven (7/50, 14.0%) responders developed additional antibodies. Two delayed hemolytic transfusion reactions (DHTRs) were reported. Reflexive extended antigen‐matching cost $4,619,133 over the 5‐year period; projected costs of prophylactic limited and extended antigen matching were $9,578,253 (+107%) and $14,537,373 (+215%), respectively. Discussion Acknowledging the limitation of excluding some responders, the rates of alloimmunization and DHTRs, and comparatively low costs suggest that reflexive extended antigen matching is viable for selected settings.