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The homozygous FcgammaRIIIa-158V genotype is a risk factor for heparin-induced thrombocytopenia in patients with antibodies to heparin-platelet factor 4 complexes.

Abstract
We hypothesized that Fcgamma receptor IIIa (FcgammaRIIIa), a polymorphic receptor for the Fc portion of immunoglobulin G (IgG) other than FcgammaRIIa, was involved in heparin-induced thrombocytopenia (HIT). FcgammaRIIa-131 and FcgammaRIIIa-158 genotypes were determined in 102 patients with definite HIT and in 2 control groups of patients treated by heparin (86 subjects without detectable antibodies [Abs] to heparin-platelet factor 4 [H/PF4], Ab(-) group; 84 patients with Abs to H/PF4 without HIT, Ab(+) group). There were no significant differences in genotype distribution or allele frequencies between the 3 groups for FcgammaRIIa-131H/R polymorphism. In contrast, FcgammaRIIIa-158V homozygotes were more frequent in the HIT group than in the Ab(+) group (P = .02), a difference that was more pronounced in patients with high levels of anti-H/PF4 Abs (P = .01). Since anti-H/PF4 Abs are mainly IgG1 and IgG3, clearance of sensitized platelets may be increased in patients homozygous for the FcgammaRIIIa-158V allotype, thus contributing to the development of thrombocytopenia.
AuthorsYves Gruel, Claire Pouplard, Dominique Lasne, Charlotte Magdelaine-Beuzelin, Chloé Charroing, Hervé Watier
JournalBlood (Blood) Vol. 104 Issue 9 Pg. 2791-3 (Nov 01 2004) ISSN: 0006-4971 [Print] United States
PMID15191947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD
  • Autoantibodies
  • FCGR3A protein, human
  • Fc gamma receptor IIA
  • Receptors, IgG
  • Platelet Factor 4
  • Heparin
Topics
  • Antigens, CD (genetics)
  • Autoantibodies (blood)
  • Case-Control Studies
  • Gene Frequency
  • Heparin (adverse effects, immunology)
  • Homozygote
  • Humans
  • Platelet Factor 4 (immunology)
  • Polymorphism, Single Nucleotide (physiology)
  • Receptors, IgG (genetics)
  • Risk Factors
  • Thrombocytopenia (chemically induced, genetics, immunology)

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