High prevalence of weakDtype 42 in a large‐scaleRHDgenotyping program in the province ofQuebec (Canada)

Abstract

Background: The determination of the RhD phenotype is crucial to avoid alloimmunization, especially in childbearing women. Following the 2015 recommendation from the Work Group on RHD Genotyping, a large-scale RHD genotyping program was implemented in the province of Quebec (Canada) and offered to women ≤45 years old with a serological weak D or discordant results. Since weak D type 42 was previously shown to be prevalent among French Canadians, genotyping for that variant was also performed. Our aim was to report the prevalence of the weak D alleles in the province of Quebec.Study Design and Methods: A retrospective study of 2105 women with serological weak D referred to Hema-Quebec's immunohematology reference laboratory (IRL) between June 2016 and May 2020 was conducted. Results from the serological tests performed by the referring hospital were compiled and RHD were genotyped.Results: Most patients presented at least one serological result ≤2+ before being referred to Hema-Quebec. Weak D type 42 was the most prevalent variant, representing 17.5% (368/2105) of all individuals tested. Only 15.3% (323/2105) of patients were weak D type 1, 3.3% (69/2105) were type 2, and 8.6% (180/2105) were type 3. Weak D type 42 is highly expressed in regions with low immigration rate and known for their founder effect. Conclusion: Our RHD genotyping program allowed for a better management of weak D. The province of Quebec presents a unique RHD genotype distribution. We confirmed that weak D type 42 is associated with a founder effect found in Caucasian French Canadians. K E Y W O R D Sfounder effect, genetics, RHD genotyping, serological testing, weak D | INTRODUCTIONRh is one of the most clinically important blood groups in transfusion medicine. It is encoded by the highly homologous RHD and RHCE genes. The determination of the RhD expression is crucial to transfusion medicine and genetic variations need to be accounted for to avoid Rh incompatibility, and prevent alloimmunization and

RHD genotyping to resolve weak and discrepant RhD patient phenotypes

“…Notably, 56% (15/27) of our patients with partial D variants had 3–4+ IS tube typings and would have been missed in some genotyping decision protocols. 4 , 7 , 8 RHD genotyping results changed RhIG or RBC transfusion management in 43% of our cohort. A high proportion of ethnically diverse patients and over one‐third of White patients with weak or discrepant D phenotypes had RHD genotypes warranting D‐negative management.…”

“… 1 , 2 However, in automated RhD typing systems with diverse methods and reagents, there is limited disparate information on how to efficiently define weak D phenotypes needing RHD allele determination. 3 , 4 , 5 , 6 , 7 , 8 , 9 Furthermore, previously United States and Canadian studies have not prospectively examined the clinical impact of RHD genotyping on ensuing needs for D‐negative RBC transfusions. We sought to examine these issues after initiating RHD genotyping in our transfusion service.…”

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

“…Therefore, the high prevalence of weak D type 42 in Québec does not appear to increase the overall prevalence of weak D phenotypes. Instead, other weak D phenotypes seemingly exhibit a lower prevalence that offsets the high prevalence of weak D type 42 (e.g., the prevalence of weak D type 1 among weak D phenotypes: 15.3% in the Leiva‐Torres et al study [7] and 24.9%–79.0% in other studies). These results may prove useful to conduct risk analyses that will inform the clinical management of patients with weak D phenotypes.…”

“…The epidemiology of this phenotype is, however, little documented. In a recent study conducted in Québec, 17.48% of women aged ≤45 with an atypical D typing result had weak D type 42, whereas only 15.3% had type 1, 3.3% had type 2 and 8.6% had type 3 [7]. Furthermore, Leiva‐Torres et al recently showed that the regional prevalence of weak D type 42 was negatively correlated with the proportion of minorities consistent with a founder effect [7].…”

“…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]. This variant is characterized by a K409M mutation at the C-terminus of RhD [8], which is predicted to be located intracellularly [3].…”