TY - JOUR
T1 - Estimating the serological underrecognition of patients with weak or partial RHD variants
AU - Ramsey, Glenn
AU - Barriteau, Christina M.
N1 - Publisher Copyright:
© 2024 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.
PY - 2024/5
Y1 - 2024/5
N2 - Background: For patients with weak or discrepant RhD RBC phenotypes, RHD genotyping is employed to determine need for RhD-negative management. However, many RHD variants are type D-negative or D-positive. Serological recognition rates (RRs) of weak and partial RHD variants are poorly characterized. Study Design and Methods: Four US studies employing RHD genotyping for weak or discrepant RhD phenotypes provided data for race/ethnicity-specific serological recognition. Three studies used microplate, and 1 used gel and tube; 2 had anti-D data. We obtained White and Hispanic/Latino allele frequencies (AFs) of weak D types 1, 2, and 3 single-nucleotide variants (SNVs) from the Genome Aggregation Database (gnomAD, v4.0.0) and devised Hardy–Weinberg-based formulas to correct for gnomAD's overcount of hemizygous RHD SNVs as homozygous. We compiled common partial RHD AF from genotyped cohorts of US Black or sickle cell disease subjects. From variant AF, we calculated hemizygous-plus-homozygous genetic prevalences. Serological prevalence: genetic prevalence ratios yielded serological RRs. Results: Overall RRs of weak D types 1–3 were 17% (95% confidence interval 12%–24%) in Whites and 12% (5%–27%) in Hispanics/Latinos. For eight partial RHD variants in Blacks, overall RR was 11% (8%–14%). However, DAR RR was 80% (38%–156%). Compared to microplate, gel–tube recognition was higher for type 2 and DAU5 and lower for type 4.0. Anti-D was present in 6% of recognized partial RHD cases, but only in 0.7% of estimated total genetic cases. Discussion: Based on AF, >80% of patients with weak or partial RHD variants were unrecognized serologically. Although overall anti-D rates were low, better detection of partial RHD variants is desirable.
AB - Background: For patients with weak or discrepant RhD RBC phenotypes, RHD genotyping is employed to determine need for RhD-negative management. However, many RHD variants are type D-negative or D-positive. Serological recognition rates (RRs) of weak and partial RHD variants are poorly characterized. Study Design and Methods: Four US studies employing RHD genotyping for weak or discrepant RhD phenotypes provided data for race/ethnicity-specific serological recognition. Three studies used microplate, and 1 used gel and tube; 2 had anti-D data. We obtained White and Hispanic/Latino allele frequencies (AFs) of weak D types 1, 2, and 3 single-nucleotide variants (SNVs) from the Genome Aggregation Database (gnomAD, v4.0.0) and devised Hardy–Weinberg-based formulas to correct for gnomAD's overcount of hemizygous RHD SNVs as homozygous. We compiled common partial RHD AF from genotyped cohorts of US Black or sickle cell disease subjects. From variant AF, we calculated hemizygous-plus-homozygous genetic prevalences. Serological prevalence: genetic prevalence ratios yielded serological RRs. Results: Overall RRs of weak D types 1–3 were 17% (95% confidence interval 12%–24%) in Whites and 12% (5%–27%) in Hispanics/Latinos. For eight partial RHD variants in Blacks, overall RR was 11% (8%–14%). However, DAR RR was 80% (38%–156%). Compared to microplate, gel–tube recognition was higher for type 2 and DAU5 and lower for type 4.0. Anti-D was present in 6% of recognized partial RHD cases, but only in 0.7% of estimated total genetic cases. Discussion: Based on AF, >80% of patients with weak or partial RHD variants were unrecognized serologically. Although overall anti-D rates were low, better detection of partial RHD variants is desirable.
KW - Rh blood group system
KW - blood grouping and crossmatching
KW - gene frequency
KW - phenotype
KW - polymorphism
KW - single nucleotide variants
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U2 - 10.1111/trf.17810
DO - 10.1111/trf.17810
M3 - Article
C2 - 38634174
AN - SCOPUS:85190991579
SN - 0041-1132
VL - 64
SP - 920
EP - 928
JO - Transfusion
JF - Transfusion
IS - 5
ER -