HEPARIN-INDUCED THROMBOCYTOPENIA - NEW INSIGHTS INTO THE IMPACT OF THE FC-GAMMA-RIIA-R-H131 POLYMORPHISM

Heparin-induced thrombocytopenia (HIT), a severe complication of hepar in treatment, can be associated with new thrombotic complications. HIT antibodies activate platelets via the platelet Fc gamma-receptor (Fc gamma RIIa), which carries a functionally relevant polymorphism (Fc ga mma RIIa-R-H131). The effect of this polymorphism on the clinical mani festations of HIT is controversial. We determined prospectively the Fc gamma RIIa-R-H131 genotypes in 389 HIT patients, in 351 patients with thrombocytopenia or thrombosis due to causes other than HIT and witho ut detectable HIT antibodies, and in 256 healthy blood donors. For thi s purpose, a novel nested sequence-specific primer-polymerase chain re action (SSP-PCR) was developed. Fc gamma RIIa-R/R131 was found to be o verrepresented in the HIT patients (27%) compared with the control gro ups (non-HIT patients [21%] and blood donors [20%]). In a subgroup of 122 well-characterized HIT patients, the genotype distribution in pati ents presenting with thrombocytopenia only was compared with that of p atients who developed thromboembolic complications. The frequency of F c gamma RIIa-R/R131 among patients with thrombotic events was signific antly elevated (37% v 17%; P =.036). Our results indicate that genotyp e distribution can be correlated to the clinical outcome of patients w ith HIT. We speculate that the reduced clearance of immune complexes i n patients with the Fc gamma RIIa-R/R131 allotype causes prolonged act ivation of endothelial cells and platelets, thus increasing the risk f or thrombotic complications. (C) 1998 by The American Society of Hemat ology.