Variant RHD alleles and Rh immunization in patients with sickle cell disease

Br J Haematol. 2023 Jun;201(6):1220-1228. doi: 10.1111/bjh.18774. Epub 2023 Apr 1.

Abstract

RH diversity among patients and donors contributes to Rh immunization despite serologic Rh-matched red cell transfusions. Anti-D can occur in D+ patients with RHD variants that encode partial D antigens. Anti-D has also been reported in patients with conventional RHD transfused primarily with units from Black donors who frequently have variant RHD. We report 48 anti-D in 690 D+ transfused individuals with sickle cell disease, categorized here as expressing conventional D, partial D or D antigen encoded by RHD*DAU0. Anti-D formed in a greater proportion of individuals with partial D, occurred after fewer D+ unit exposures, and remained detectable for longer than for those in the other categories. Among all anti-D, 13 had clinical or laboratory evidence of poor transfused red cell survival. Most individuals with anti-D were chronically transfused, including 32 with conventional RHD who required an average of 62 D- units/year following anti-D. Our findings suggest that patients with partial D may benefit from prophylactic D- or RH genotype-matched transfusions to prevent anti-D. Future studies should investigate whether RH genotype-matched transfusions can improve use of valuable donations from Black donors, reduce D immunization and minimize transfusion of D- units to D+ individuals with conventional RHD or DAU0 alleles.

Keywords: RH genetics; RhD; alloimmunization; red blood cell transfusion; sickle cell disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Anemia, Sickle Cell* / genetics
  • Anemia, Sickle Cell* / therapy
  • Blood Transfusion
  • Genotype
  • Humans
  • Immunization
  • Phenotype
  • Rh-Hr Blood-Group System* / genetics

Substances

  • Rh-Hr Blood-Group System