Potential Benefits of Extended Genotype Matching to Chronically Transfused Patients with Sickle Cell Disease

Management of RBC alloimmunization in Sickle Cell Disease (SCD) patients has been the subject of much debate, and currently there is no standard approach. Many programs transfuse SCD patients with RBCs that are phenotype-matched for D, C, c, E, e and K. Although these approaches reduce the incidence of alloantibody production, patients still become alloimmunized. Based on this we aimed to identify the rates of alloimmunization in chronically transfused SCD patients and compare the phenotyping with genotyping methods to find a better way to match RBC units to those patients. Methods: We selected 45 SCD patients (homozygous for hemoglobin S) with multiple transfusions, previously phenotyped for ABO, Rh (D, C, c, E, e) and K1. Phenotypes were determined by hemagglutination using gel cards (Diamed® ). Genotypes were determined by a DNA array using the Human Erythrocyte Antigen BeadChip (“HEA”) from Bioarray Solutions. All SCD patients included in this study were in chronical transfusion program; receiving multiple transfusions. The median age was 24y; there were 28(62%) females and 17(37.8%) males. The median of transfusions were 53 (5–78) and 40 (88.9%) patients received more than 20 phenotype-matched units for Rh (D, C, c, E, e) and K1. Results: Of the 45 SCD patients selected, 11 (24.4%) had alloantibodies. The antibody specificities found in these patients were anti-D, -C, -C^W, -E, -Jk^a, -Jk^b, -Fy^a, -Di^a, -s. Although the patients were receiving Rh and K phenotype-matched units 8 (17%) of them became alloimmunized to Rh antigens and on those patients we found discrepancies between the previous phenotype and genotype-derived phenotype. Our results showed that the risk of immunization increases in patients over 40 years old (p= 0.05) and with the number of transfusion events. Patients with more than 20 RBC transfusions have a tendency for alloimmunization (p=0.65). We also observed that genotyping was more effective than hemagglutination in determining patient's correct phenotype. Conclusion: Our data show that even with the implementation of Rh and K phenotype-matching in chronically transfused patients with SCD, they still become alloimmunized to other antigens with high immunization risk and also to Rh antigens due to the limitations of the hemagglutination. The relevance of genotype determination of blood groups for the management of multiple transfused patients with SCD has been demonstrated by allowing the determination of the true blood group genotype, by assisting in the identification of suspected alloantibodies and in the selection of antigen-negative. As donor genotyping for the most clinically relevant blood group antigens by automated DNA techniques are becoming available, extended genotype matching should be considered in this group of patients.

No relevant conflicts of interest to declare.