Carlsson L E, Santoso S, Baurichter G, Kroll H, Papenberg S, Eichler P, Westerdaal N A, Kiefel V, van de Winkel J G, Greinacher A
Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Blood. 1998 Sep 1;92(5):1526-31.
Heparin-induced thrombocytopenia (HIT), a severe complication of heparin treatment, can be associated with new thrombotic complications. HIT antibodies activate platelets via the platelet Fcgamma-receptor (FcgammaRIIa), which carries a functionally relevant polymorphism (FcgammaRIIa-R-H131). The effect of this polymorphism on the clinical manifestations of HIT is controversial. We determined prospectively the FcgammaRIIa-R-H131 genotypes in 389 HIT patients, in 351 patients with thrombocytopenia or thrombosis due to causes other than HIT and without detectable HIT antibodies, and in 256 healthy blood donors. For this purpose, a novel nested sequence-specific primer-polymerase chain reaction (SSP-PCR) was developed. FcgammaRIIa-R/R131 was found to be overrepresented in the HIT patients (27%) compared with the control groups (non-HIT patients [21%] and blood donors [20%]). In a subgroup of 122 well-characterized HIT patients, the genotype distribution in patients presenting with thrombocytopenia only was compared with that of patients who developed thromboembolic complications. The frequency of FcgammaRIIa-R/R131 among patients with thrombotic events was significantly elevated (37% v 17%; P = .036). Our results indicate that genotype distribution can be correlated to the clinical outcome of patients with HIT. We speculate that the reduced clearance of immune complexes in patients with the FcgammaRIIa-R/R131 allotype causes prolonged activation of endothelial cells and platelets, thus increasing the risk for thrombotic complications.
肝素诱导的血小板减少症（HIT）是肝素治疗的一种严重并发症，可能与新的血栓形成并发症相关。HIT抗体通过血小板Fcγ受体（FcγRIIa）激活血小板，该受体存在一种具有功能相关性的多态性（FcγRIIa-R-H131）。这种多态性对HIT临床表现的影响存在争议。我们前瞻性地测定了389例HIT患者、351例因非HIT原因导致血小板减少或血栓形成且未检测到HIT抗体的患者以及256名健康献血者的FcγRIIa-R-H131基因型。为此，开发了一种新型巢式序列特异性引物聚合酶链反应（SSP-PCR）。与对照组（非HIT患者[21%]和献血者[20%]）相比，FcγRIIa-R/R131在HIT患者中比例过高（27%）。在122例特征明确的HIT患者亚组中，比较了仅出现血小板减少的患者与发生血栓栓塞并发症患者的基因型分布。发生血栓事件的患者中FcγRIIa-R/R131的频率显著升高（37%对17%；P = 0.036）。我们的结果表明，基因型分布与HIT患者的临床结局相关。我们推测，具有FcγRIIa-R/R131同种异型的患者中免疫复合物清除减少会导致内皮细胞和血小板的长期激活，从而增加血栓形成并发症的风险。
