Impact of RHD genotyping on transfusion practice in Denmark and the United States and identification of novel RHD alleles

Abstract

Background Reduced D antigen on red blood cells (RBCs) may be due to “partial” D phenotypes associated with loss of epitope(s) and risk for alloimmunization or “weak” D phenotypes that do not lack major epitopes with absence of clinical complications. Genotyping of samples with weak and discrepant D typing is recommended to guide transfusion and RhIG prophylaxis. The goal was to compare the impact of RHD genotyping on transfusion practice in two centers serving different populations. Study Design and Methods Fifty‐seven samples from Denmark and 353 from the United States with weak or discrepant D typing were genotyped. RBC typing was by multiple methods and reagents. DNA isolated from white blood cells was tested with RBC‐Ready Gene D weak or CDE in Denmark or RHD BeadChip in the United States. RHD was sequenced for those unresolved. Results Of Caucasian samples from Denmark, 90% (n = 51) had weak D types 1, 2, or 3; two had other weak D, two partial D, and two new alleles. In diverse ethnic U.S. samples, 44% (n = 155) had weak D types 1, 2, or 3 and 56% (n = 198) had other alleles: uncommon weak D (n = 13), weak 4.0 (n = 62), partial D (n = 107), no RHD (n = 9), and new alleles (n = 7). Conclusion Most samples with weak or variable D typing from Denmark had alleles without risk for anti‐D. In U.S. samples, 48% could safely be treated as D+, 18% may require consideration if pregnancy possible, and 34% could potentially benefit from being treated as D–. Black and multiracial ethnicities were overrepresented relative to population.

Molecular and serological analysis of the D variant in the Chinese population and identification of seven novel RHD alleles

“…The working group recommends RHD genotyping for patients with serologically weak D phenotype and suggests that weak D types 1, 2, and 3 patients can be safely managed as D+. However, the RHD weak D type 1 , 2 , and 3 alleles, the most frequent weak D alleles in Caucasians, 11–14 were not identified or rarely detected in our study and other previous reports in the Chinese population 16,17,22,28–32 . Therefore, detecting weak D type 1 , 2 , and 3 alleles for Chinese D variant patients is unnecessary.…”

“…The molecular events underlying the D variants differ greatly by ethnicity. 10 For example, RHD*weak D types 1, 2, and 3 are the most common molecular background of the D variant phenotype in Caucasians, 5,[11][12][13][14][15] whereas RHD*weak partial 15 and RHD*DVI.3 are the most common RHD alleles in Chinese D variant individuals. 16,17 Therefore, each region should have a population-specific RhD serological and genetic typing strategy based on the spectrum of prevalent RHD variant alleles.…”

“…16,17 Therefore, each region should have a population-specific RhD serological and genetic typing strategy based on the spectrum of prevalent RHD variant alleles. 18 The molecular basis of the D variants in Caucasians and individuals of African descent have been well described, 5,[11][12][13][14][15]18 and several genotyping platforms have been established and validated to determine the common RHD variant alleles in these populations. [19][20][21] However, the molecular genetic data and serological results of Chinese D variants have been comparatively less studied, 16,17,22 and there are no suitable typing strategies or test kits available for Chinese D variants.…”

RHD genotyping to resolve weak and discrepant RhD patient phenotypes

“…15 Zygosity was undetermined unless heterozygous variants were detected. Reference RHD analysis (New York Blood Center 16 ) was obtained in one case with exon-specific low signals. One case underwent DNA-based RBC phenotyping (HEA BeadChip, Immucor BioArray Solutions, Warren, NJ).…”

Prevalence of weak D phenotypes in the general population of Québec, Canada: A focus on weak D type 42

“…In predominantly White populations, weak D types 1, 2 or 3 are generally the most prevalent weak D phenotypes [3][4][5][6]. One exception is Québec (Canada), where weak D type 42 (conferred by RHD*01W.42) is the most common weak D phenotype [7].…”