Children's Hospital of Philadelphia Philadelphia, Pennsylvania, United States
Background/Case Studies: Alloimmunization is a significant complication among transfused patients with sickle cell disease (SCD) despite serologic Rh and K antigen matching. This leads to hemolytic transfusion reactions, limits compatible donors, and impacts patient outcomes. A prior study in patients with SCD reported a mean of 3.5 mismatched antigen exposures per Rh and K-matched transfusion from the general blood donor inventory (n=627 transfusions). Since antigen frequency varies by race, transfusion with Rh and K-matched donor units from similar racial background may minimize non-self red cell antigen exposure and alloimmunization.
Study
Design/Methods: We investigated non-Rh antigen mismatches among 21 patients with SCD receiving chronic transfusion therapy on 2 RH genotype matching clinical trials with provision of units from Black and Hispanic donors (NCT04156893,NCT04156906). Patients and donors were genotyped using the Human Erythrocyte Antigen (HEA) Beadchip (Werfen, Warren, NJ) that predicts expression of 35 antigens in 11 systems. All patients were transfused RH genotype and K-matched units. We compared donor and recipient red cell antigen genotypes and the number of non-self antigens exposed per unit and transfusion visit.
Results/Findings: Among 21 patients, 18 self-identified as Black, 2 Hispanic, and 1 Black/Hispanic. Prior to enrollment, this cohort had received 5,013 Rh and K-matched units, and 8 patients were alloimmunized with 16 total antibodies: 5 anti-D, 2 anti-Kpa, and 1 each of anti-V, -C, -Goa, -K, -Jsa, -Lea, -He, -Lu14, -Lsa. Overall, 468 and 50 units from Black and Hispanic donors, respectively, were transfused. All patients and donors were predicted to express high prevalence k, Jsb, s, U, Lub, Dib, Coa, Hy, Joa, LWa, Sc1, and lack LWb. No patient was at risk for anti-Fyb since they were either Fy(b+) or had the GATA site mutation in DARC. Patient vs donor antigen frequency is summarized in Table 1. Nineteen Black or Black/Hispanic recipients received 487 units from 456 Black and Hispanic donors; the mean number of mismatched antigen exposures was 1.28 per unit (range 0.19-3.36) and 1.55 per transfusion (range 0.33-3.80). The 2 Hispanic recipients received 31 units from 25 donors; the mean number of mismatched antigen exposures was 1.19 per unit (range 1.18-1.22) and 1.75 per transfusion (range 1.22-2.43). The most frequently mismatched antigen exposures were Jkb, S, and Doa. Among 518 units transfused, one anti-Jkb occurred during the study, for a rate of 0.19 antibodies per 100 units transfused. Conclusions: Patients with SCD who identify as Black or Hispanic were exposed to fewer non-self antigens when transfused with red cell units from Black and Hispanic donors, which resulted in a low alloimmunization rate (1 antibody in 500 units transfused).
