Impact of Extended Molecular RBC Antigen Matching between Blood Donors and Patients with Hematological Diseases

Background: Programs to prevent alloimmunization against red RBC antigens aims to provide antigen-compatible blood transfusions for patients with hematological diseases. Recently, there is an emerging role of molecular methods in donor-receptor compatibility for major blood group polymorphisms and for Rh variants to improve transfusion safety.

Aims: We aimed to determine the genotype and allele frequencies of major blood-group systems and RHD and RHCE variants in blood donors and patients with SCD, Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML) or Autoimmune Hemolytic Anemia (AIHA) to verify if the genotyping results are in concordance with serologic typing results and to perform molecular compatibility between donors and patients.

Methods: Samples from 198 blood donors were phenotyped for five clinically relevant blood-group system antigens (RH, KEL, JK, FY and MNS). Samples from 158 patients with hematological diseases (101 with SCD, 14 with MDS, 26 with AIHA and 17 with AML) and from 198 blood donors were evaluated molecularly for 18 blood-group systems alleles (RH, CO, CROM, DI, DO, FY, GE, IN, JK, KEL, KN, LE, LU, LW, MNS, OK, SC and YT) using the Blood-MLPA assay (Multiplex Ligation-dependent Probe Amplification). RHD and/or RHCE exon-specific sequencing was performed to discriminate RHD and RHCE subtypes not distinguished by MLPA. Computerized molecular matching was performed between all patients and donors for ABO, RH, MNS, KEL, FY, JK and DI blood-group systems (Level 1). Afterwards, we extended the matching degree [ABO, RH (further variants), MNS, KEL, FY, JK and DI (Level 2)] for patients who inherit clinically relevant RHD and/or RHCE genotypes predicting partial Rh antigens.

Results: We found statistically significant differences in the frequencies of the blood group alleles MNS, FY, JK, DO, CO, GE and RH (RHD*DAU0, RHCE*ceVS.01, RHCE*Ce and RHCE*CE) between donors and patients with hematological diseases. The allelic profile of AML patients was the most similar to the allelic profile of donors, while that of SCD patients was the most different. Eight donors and nine patients had clinically relevant RHD genotypes, while 14 donors and 22 patients had clinically relevant RHCE genotypes. There was 99.2% concordance between the results of the serologic typing and the results of the predicted phenotypes by the blood-MLPA. Considering the Level 1 matching It would be possible to find at least one compatible blood donor for 91.1% patients with hematological diseases. From recently transfused patients (i.e., those transfused up to one year prior to participation in the study), 70.3% would have enough blood units for an annual transfusion cycle. The MDS patient group were the least attended with matched blood (55.6%) and the one with the lowest number of compatible donors (85.7%). Taking into consideration the Level 2 matching the average number of available donors per patient reduced from 19.7 to 3.5 when the degree of matching was extended (i.e., from Level 1 to Level 2). Besides, the number of compatible donors was not sufficient to fulfil the transfusion needs of patients with Rh variants.

Conclusion: We reliably determine the genotype and allele frequencies of clinically relevant blood-group systems in donors and in patients using molecular methods. It would be possible to meet the transfusion needs of most patients with hematological diseases through molecular compatibility, but the current donor population would not fill the transfusion requirements of patients with Rh variants. Molecular RBC matching increases the safety of patients with SCD, MDS, AML and AIHA by providing more accurate compatibility with genotyped donors and by reducing the risk of transfusion reactions.