The homozygous FcgammaRIIIa-158V genotype is a risk factor for heparin-induced thrombocytopenia in patients with antibodies to heparin-platelet factor 4 complexes.
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.
Gruel
Yves
Y
Department of Hematology-Hemostasis, Centre Hospitalier Universitaire Tours, Institut National de la Santé et de la Recherche Médicale U618, Tours, France. gruel@med.univ-tours.fr
Pouplard
Claire
C
Lasne
Dominique
D
Magdelaine-Beuzelin
Charlotte
C
Charroing
Chloé
C
Watier
Hervé
H
D015703:Antigens, CD / Q000235:genetics; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D005787:Gene Frequency; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006720:Homozygote; D006801:Humans; D010978:Platelet Factor 4 / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D017452:Receptors, IgG / Q000235:genetics*; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D001323:Autoantibodies; C496124:FCGR3A protein, human; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D010978:Platelet Factor 4; D006493:Heparin