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 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 genotype may mitigate Rh alloimmunization, but the feasibility and resources required are not known. We compared allele frequencies between patients with SCD (n = 857) and African American donors (n = 587) and showed that allele frequencies are similar. Overall, 29% of and 53% of alleles are altered in patients and African American donors. We modeled 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 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 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 genotyping all minority donors and management of the data remain limiting factors.

Molecular matching for patients with haematological diseases expressing altered RHD‐RHCE genotypes

“…Chou et al [46], recently found that the RH allele frequencies between patients with SCD and African American donors are similar. Besides, SCD patients and African American donors studied by Chou et al inherit more altered RHD and RHCE alleles than SCD patients and donors included in our study.…”

Supplemental findings of the 2017 National Blood Collection and Utilization Survey

“…Persons with the same race and ethnicity are more likely to have the same major and minor blood antigens and transfusing blood to recipients from donors with the same race and ethnicity can reduce the risk of complications related to mismatched antigens . For example, persons with sickle cell disease can require frequent transfusions and are at a high risk of developing alloantibodies; recruiting donors from racially diverse populations for blood antigen matching can reduce the risk of alloimmunization . New thresholds which have increased the minimum Hgb for male donors may have resulted in more deferrals of black males compared to other races, likely because healthy black males have been reported to have lower Hgb level than white males .…”

“…37 For example, persons with sickle cell disease can require frequent transfusions and are at a high risk of developing alloantibodies; recruiting donors from racially diverse populations for blood antigen matching can reduce the risk of alloimmunization. [38][39][40] New thresholds which have increased the minimum Hgb for male donors may have resulted in more deferrals of black males compared to other races, likely because healthy black males have been reported to have lower Hgb level than white males. 25,35,41 Strategic planning tools to increase African-American blood donation are available, 37 but additional studies to determine effective methods to increase donations among minorities are needed.…”

Developments beyond blood group serology in the genomics era

“…While it is proposed that improved RH allele matching would decrease this rate of alloimmunisation in SCD patients, this raises the question as to whether matching is possible with current blood donor demographics, given that these RH alleles are not prevalent amongst European donors. Chou et al () showed first that RH allele frequencies between SCD patients ( n = 857) and African American donors ( n = 587) were similar. They then applied statistical modelling to estimate the donor recruitment that would be required to provide additional ‘prophylactic RH genetic matching’ (along with Rh and Kell serology matching).…”