The RHD(1227G>A) DEL‐associated allele is the most prevalent DEL allele in Australian D– blood donors with C+ and/or E+ phenotypes

Background Red blood cells (RBCs) with D antigen levels only detected by anti-D adsorption-elution and an antiglobulin test express a DEL phenotype. For two DEL types, including RHD(1227G>A), immunization of D– recipients has been reported. This study's aim was to measure the prevalence of DEL-associated RHD alleles in a cohort of Australian D– donors to develop a model to estimate alloimmunization risk. Study Design and Methods D–, C+ and/or E+ blood donors were screened for RHD exons using quantitative polymerase chain reaction. Donors with RHD signals were DEL phenotyped with MCAD6 anti-D. RHD alleles were characterized via single-nucleotide polymorphism array or sequencing. Extended DEL phenotyping was performed with an anti-D panel. Results Among 2027 donors, 39 carried RHD alleles that have been previously reported to associate with either the DEL or the weak D phenotype. An additional five donors carried previously unreported RHD alleles and exhibited the DEL phenotype: RHD(IVS2-2delA), RHD(IVS1+5G>C), RHD(ex9:del/CE), and RHD(ex8:del/CE) represented twice. In total, DEL/weak D–associated RHD alleles were detected in 44 of 2027 donors or 2.17% (95% confidence interval, 1.54%-2.81%). The RHD(1227G>A) DEL allele was the most frequent (n = 16). The risk of transfusing D– females not more than 40 years of age with an RHD(1227G>A) DEL RBC unit (when managed as D–) is estimated to be one in 149,109 transfusions (range, 100,680-294,490). Conclusion DEL/weak D–associated RHD alleles were found in 2.17% of Australian D–, C+ and/or E+ blood donors. This differs from previous European reports in that the clinically significant RHD(1227G>A) DEL allele is the most prevalent.