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Clinical pathology selected abstracts

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Editor: Deborah Sesok-Pizzini, MD, MBA, professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and chief, Division of Transfusion Medicine, Children’s Hospital of Philadelphia.

RH genotype matching for transfusion support in sickle cell disease

January 2019—In patients with sickle cell disease, Rh alloimmunization remains a challenge, despite the transfusion of serologic Rh C, E, and K antigen-matched red cells. The rates of alloimmunization are due to the complexity of the Rh blood group system, which includes more than 50 antigens defined at the serologic level, encoded by the RHD and RHCE genes. The degree of RH genetic diversity is higher in African populations than in Europeans, who represent the majority of blood donors. Approximately 85 percent of African-American patients with sickle cell disease carry at least one RH allele that differs from that commonly found in white blood donors, causing some patients to recognize donor antigens as foreign. RH genotype matching may be used to mitigate the risk of alloimmunization, but its feasibility is unknown. The authors evaluated the efficacy of serologic matching, compared RH allele frequencies between patients with sickle cell disease and African-American donors, and created a model of RH genotype matching. They found that during the four-year period of 2013 through 2016, 105 of 550 (19 percent) patients who received at least one blood transfusion using serologic testing with units selected primarily from African-American donors developed antibodies. Their analysis suggested that 50 percent of these cases may result from D-, C-, and E-like cross-reactive epitopes stimulated by African-American donor cells—a rate that may be mitigated by providing genetically matched red cells at the RH loci. The authors also compared RH allele diversity between their patient population (n = 857) and African-American donors (n = 587) and found it to be comparable, with 29 percent of RHD and 53 percent of RHCE alleles altered in sickle cell disease patients and African-American donors. They modeled four matching strategies: serologic DCEK matched; serologic DCEK with extended antigens matched; RH genotype and K matched; and RH genotype, K, and extended antigen matched. Their model showed that Rh matching based on RH genotype and K status met 95 percent of their patients’ needs if twice as many African-American donors were collected each weekday. A much smaller increase in donors is necessary if less restrictive genetic matching is employed. For each of the four algorithms, a donor pool consisting primarily of African-Americans is necessary to avoid depleting D− units. In summary, RH-genotype–matched red cells may reduce rates of alloimmunization in patients with sickle cell disease and may be feasible from an inventory perspective. While African-American donor recruitment may be a challenge, the authors point out that strategies used by some blood centers have been successful. They also note that the cost of RH genotyping may be prohibitive, but this factor is likely to resolve as sequencing approaches continue to improve.

Chou ST, Evans P, Vege S, et al. RH genotype matching for transfusion support in sickle cell disease. Blood. 2018;132(11):1198–1207.

Correspondence: Dr. Stella T. Chou at chous@email.chop.edu

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