RHD variants in Flanders, Belgium

Transfusion. 2015 Jun;55(6 Pt 2):1411-7. doi: 10.1111/trf.12947. Epub 2014 Nov 21.


Background: D antigen variants may be grouped into partial D, weak D, and DEL types. Cumulative phenotype frequencies of these D variants may approach 1% in certain European regions. Unambiguous and quick identification of D variants is of immediate clinical relevance, with implications for transfusion strategy.

Study design and methods: A total of 628 samples with ambiguous serologic results from different immunohematology laboratories throughout the Flanders region, Belgium, were genotyped using a commercially available weak D typing approach. After exclusion of detectable weak D types, molecular RHD exon scanning was performed for the remaining samples, and RHD sequencing was performed in two particular cases.

Results: Of all samples investigated, 424 (67.5%) were positive for weak D Type 1, 2, or 3, and 22 cases (3.5%) typed weak D Type 4.0/4.1/4.3, 4.2, 5, 11, 15, or 17. Another 49 (7.8%) samples were partial D variants, with a major proportion being category DVI types (n = 27). One RHD(S103P) sample was identified as high-grade partial D, with DIII-like phenotype and anti-D and anti-C immunization. Additionally, a novel DVI Type 3 (A399T) variant was found. Of the remaining 133 samples mainly tested because of ambiguous serologic D typing results due to recent transfusion, 32 (5.1%) were negative for RHD, and 101 (16.1%) were indistinguishable from wild-type RHD and not investigated further.

Conclusion: Despite the enormous diversity of RHD alleles, first-line weak D genotyping was remarkably informative, allowing for rapid classification of most samples with conspicuous RhD phenotype in Flanders. The clinical implications are discussed.

MeSH terms

  • Alleles
  • Belgium / epidemiology
  • Blood Donors / statistics & numerical data*
  • Blood Grouping and Crossmatching* / statistics & numerical data
  • Epitope Mapping
  • Genetic Variation*
  • Genotype
  • Humans
  • Isoantibodies / blood
  • Molecular Sequence Data
  • Phenotype
  • Polymerase Chain Reaction / methods
  • Rh-Hr Blood-Group System / genetics*
  • Rh-Hr Blood-Group System / immunology
  • Rho(D) Immune Globulin


  • Isoantibodies
  • RHO(D) antibody
  • Rh-Hr Blood-Group System
  • Rho(D) Immune Globulin
  • Rho(D) antigen

Associated data

  • GENBANK/FR748227