Bachelot-Loza C, Saffroy R, Lasne D, Chatellier G, Aiach M, Rendu F
Inserm U 428, Faculté des Sciences pharmaceutiques, Paris, France.
Thromb Haemost. 1998 Mar;79(3):523-8.
Heparin-induced thrombocytopenia (HIT) involves heparin-dependent antibodies which induce platelet activation. In the present study, we searched for a relationship between the polymorphism of the Fc receptor (FcgammaRIIa) and the development of HIT. In this purpose, all the donors were genotyped for their FcgammaRIIA and HIT patients were selected on the basis of at least one positive answer by 14C-serotonin release assay (SRA). The frequency distribution of the FcgammaRIIa polymorphism in the HIT patient group was similar to that observed in the healthy control group. Moreover, a statistical analysis taking into account our results and those of 3 previously published studies, suggested at most only a weak association between HIT and the FcgammaRIIa-131 polymorphism. Laboratory tests used to diagnose HIT rely on the activation of normal donor platelets but fail to detect every HIT positive patient. We determined the role of FcgammaRIIa-131 polymorphism on the reactivity of control platelets to HIT plasmas. When control platelet FcgammaRIIa-131 was of Arg/Arg form, only 47% of the HIT plasmas were positive by SRA, compared to 81% and 74% for His/His or His/Arg forms, respectively. We also compared the level of anti PF4/heparin antibodies in the HIT plasmas with the response obtained by SRA. The mean anti PF4/heparin antibodies level in HIT plasma was significantly lower in negative SRA than in positive tests when using control platelets from FcgammaRIIa-Arg/Arg 131 and heterozygous donors. Thus, the variability of control platelets to respond to HIT plasmas in the SRA test is related to both the FcgammaRIIa-131 polymorphism, and to the amount of anti PF4/heparin antibodies.
肝素诱导的血小板减少症（HIT）涉及诱导血小板活化的肝素依赖性抗体。在本研究中，我们探寻了Fc受体（FcγRIIa）多态性与HIT发生发展之间的关系。为此，对所有供血者进行了FcγRIIA基因分型，并根据14C - 5羟色胺释放试验（SRA）至少有一个阳性结果来选择HIT患者。HIT患者组中FcγRIIa多态性的频率分布与健康对照组中观察到的相似。此外，综合我们的结果以及之前发表的3项研究结果进行的统计分析表明，HIT与FcγRIIa - 131多态性之间至多仅有微弱关联。用于诊断HIT的实验室检测依赖于正常供血者血小板的活化，但无法检测出每一位HIT阳性患者。我们确定了FcγRIIa - 131多态性对对照血小板对HIT血浆反应性的作用。当对照血小板FcγRIIa - 131为Arg/Arg形式时，通过SRA检测，只有47%的HIT血浆呈阳性，而His/His或His/Arg形式的分别为81%和74%。我们还比较了HIT血浆中抗PF4/肝素抗体水平与SRA获得的反应情况。当使用来自FcγRIIa - Arg/Arg 131纯合子和杂合子供血者的对照血小板时，SRA检测呈阴性的HIT血浆中抗PF4/肝素抗体的平均水平显著低于呈阳性检测的血浆。因此，SRA试验中对照血小板对HIT血浆反应的变异性既与FcγRIIa - 131多态性有关，也与抗PF4/肝素抗体的量有关。
