RH genotype matching for transfusion support in sickle cell disease

Abstract

Rh alloimmunization remains a challenge for patients with sickle cell disease (SCD) despite transfusion of serologic Rh C, E, and K antigen-matched red cells. Inheritance of altered <i>RH</i> alleles contributes to the prevalence of Rh antibodies after blood transfusion in patients with SCD and explains approximately one-third of cases. The remainder seem to be stimulated by altered Rh proteins on African American donor red cells. Matching patients with donors on the basis of <i>RH</i> genotype may mitigate Rh alloimmunization, but the feasibility and resources required are not known. We compared <i>RH</i> allele frequencies between patients with SCD (n = 857) and African American donors (n = 587) and showed that <i>RH</i> allele frequencies are similar. Overall, 29% of <i>RHD</i> and 53% of <i>RHCE</i> alleles are altered in patients and African American donors. We modeled <i>RH</i> genotype matching compared with serologic Rh D, C, and E, along with K antigen matching, and found that approximately twice the number of African American donors would be required for <i>RH</i> genotype vs Rh serologic matching at our institution. We demonstrated that African American donor recruitment is necessary to maintain an adequate supply of C-, E-, and K-negative donor units to avoid depleting the Rh-negative (RhD^-) blood supply. Our results suggest that prophylactic <i>RH</i> genetic matching for patients with SCD is feasible with a donor pool comprised primarily of African-Americans and would optimize the use of our existing minority donor inventory. The current cost of <i>RH</i> genotyping all minority donors and management of the data remain limiting factors.