Red cell antigen exposures in patients with sickle cell disease receiving transfusion from Black and Hispanic donors

Patients with sickle cell disease (SCD) have an elevated risk for alloimmunization because of frequent transfusions and antigenic disparities with donors. Extended antigen matching beyond Rhesus (Rh; CcEe) and Kell (K) can reduce alloimmunization but is not broadly applied because of logistic and economic challenges. Red cell antigen exposures may be minimized when donor and patient populations are from similar racial and ethnic backgrounds. This study assessed alloantigen exposure across 35 antigens in patients with SCD who received transfusions from donors who self-identified as Black or Hispanic. Seven hundred units transfused to 28 chronically transfused patients were genotyped using a single nucleotide polymorphism-based assay. When combining Rh and K-matching with donor unit selection from racially similar populations, patients were exposed to an average of 1.6 antigens per transfusion, compared to the previously reported 3.5 exposures per transfusion across the same 35 antigens using a general donor inventory. Among 514 units transfused to Black recipients from Black donors, 22% had no foreign antigen exposure across 35 antigens. The most frequent alloantigen exposures were Jk^b, S, and Do^a. One clinically significant anti-Jk^b formed during the study. These findings suggest combining donor unit selection with blood group genotyping may improve compatibility and transfusion safety for high-risk populations. These trials were registered at www.ClinicalTrials.gov as NCT04156893 and NCT04156906.