Improving transfusion outcomes in sickle cell disease through extended red blood cell molecular matching

We evaluated the impact of extended red blood cell (RBC) molecular matching on alloimmunization and transf usion-related outcomes in patients with sickle cell disease (SCD) and assessed the frequency and clinical significance of genotype- phenotype discrepancies. We conducted a retrospective analysis of 108 transfused patients with SCD who underwent phenotyping and molecular genotyping for clinically relevant RBC antigens. Patients were divided into two groups: those who received extended serologically matched RBC units (n = 55) and those who received extended molecularly matched RBC units (n = 53). Primary outcomes included the rate of alloimmunization, incidence of delayed hemolytic transfusion reactions (DHTRs), and the identification of antigen mismatches or discrepancies between genotype and phenotype. Molecular testing revealed clinically significant antigen mismatches in 42 percent of patients. Partial RH alleles were identified in 17 percent of patients. Discrepancies between genotype and phenotype were observed in 21.3 percent of patients. Alloimmunized patients were significantly more likely to have undetected mismatches. DHTRs after transfusion with RBC units that were serologically matched, but not molecularly compatible, were observed in two patients. In conclusion, extended RBC molecular matching improves the detection of clinically relevant antigen mismatches not identified by routine serologic methods and is associated with a lower risk of alloimmunization and transfusion-related complications.