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.