Heparin-induced thrombocytopenia:: New insights into the impact of the FcγRIIa-R-H131 polymorphism
Heparin-induced thrombocytopenia:: New insights into the impact of the FcγRIIa-R-H131 polymorphism
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DOI：
10.1182/blood.v92.5.1526.417k26_1526_1531
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发表时间：
1998-09-01
期刊：
影响因子：
20.3
通讯作者：
Greinacher, A
中科院分区：
文献类型：
--
作者：
Carlsson, LE;Santoso, S;Greinacher, A
肝素诱导的血小板减少症（HIT）是肝素治疗的严重并发症，可能与新的血栓并发症有关。 HIT 抗体通过血小板 Fc γ 受体 (Fc γ RIIa) 激活血小板，该受体携带功能相关的多态性 (Fc γ RIIa-R-H131)。这种多态性对 HIT 临床表现的影响存在争议。我们前瞻性地确定了 389 名 HIT 患者、351 名因 HIT 以外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 Fc gamma RIIa-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式反应（SSP-PCR）。与对照组（非 HIT 患者 [21%] 和献血者 [20%]）相比，Fc gamma RIIa-R/R131 在 HIT 患者 (27%) 中的表达过高。在由 122 名特征明确的 HIT 患者组成的亚组中，仅将出现血小板减少症的患者的基因型分布与出现血栓栓塞并发症的患者的基因型分布进行了比较。发生血栓事件的患者中 Fc gamma RIIa-R/R131 的频率显着升高（37% vs 17%；P =.036）。我们的结果表明，基因型分布可能与 HIT 患者的临床结果相关。我们推测，Fc gamma RIIa-R/R131 同种异型患者的免疫复合物清除率降低，导致内皮细胞和血小板活化时间延长，从而增加血栓并发症的风险。 (C) 1998 年，美国血液学会。
Heparin-induced thrombocytopenia (HIT), a severe complication of heparin 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 gamma RIIa-R-H131). The effect of this polymorphism on the clinical manifestations 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 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. Fc gamma RIIa-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 Fc gamma RIIa-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 Fc gamma RIIa-R/R131 allotype causes prolonged activation of endothelial cells and platelets, thus increasing the risk for thrombotic complications. (C) 1998 by The American Society of Hematology.