Brandt J T, Isenhart C E, Osborne J M, Ahmed A, Anderson C L
Department of Pathology, Ohio State University, Columbus 43210, USA.
Thromb Haemost. 1995 Dec;74(6):1564-72.
Heparin induced thrombocytopenia (HIT) is characterized by the formation of antibodies that activate normal donor platelets in vitro in the presence of heparin. We asked whether the commonly observed donor-specific variation in the platelet aggregation response to HIT antibodies is influenced by the density of Fc gamma RII on platelets or by the Arg/His 131 allelic polymorphism of platelet Fc gamma RII. We found that platelets with His/His 131 Fc gamma RII phenotype were unresponsive to HIT antibody (0/9) whereas platelets with the Arg/Arg 131 phenotype responded well (7/9). His/His 131 platelets were largely unresponsive also to a murine IgG1 antiplatelet monoclonal antibody (UR1) known to activate platelets by Fc gamma RII clustering. We then determined the frequency distribution of Fc gamma RIIa Arg/His 131 phenotypes on a series of 200 patients evaluated for HIT and 100 non-thrombocytopenic hospitalized patients. The frequency of the His/His 131 phenotype was significantly increased (34.4%) in the 96 thrombocytopenic patients with HIT antibody compared to the 104 thrombocytopenic patients without HIT antibody and the 100 non-thrombocytopenic patients (approximately 19%). Thus, the Fc gamma RII phenotype regulates the in vitro activation response of normal platelets to HIT antibody and is a risk factor for the thrombocytopenia of HIT.
肝素诱导的血小板减少症（HIT）的特征是在肝素存在的情况下形成能在体外激活正常供体血小板的抗体。我们研究了血小板对HIT抗体的聚集反应中常见的供体特异性差异是否受血小板上FcγRII密度或血小板FcγRII的Arg/His 131等位基因多态性影响。我们发现，具有His/His 131 FcγRII表型的血小板对HIT抗体无反应（0/9），而具有Arg/Arg 131表型的血小板反应良好（7/9）。His/His 131血小板对已知通过FcγRII聚集激活血小板的鼠IgG1抗血小板单克隆抗体（UR1）也基本无反应。然后，我们确定了在一系列200例接受HIT评估的患者和100例非血小板减少症住院患者中FcγRIIa Arg/His 131表型的频率分布。与104例无HIT抗体的血小板减少症患者和100例非血小板减少症患者（约19%）相比，96例有HIT抗体的血小板减少症患者中His/His 131表型的频率显著增加（34.4%）。因此，FcγRII表型调节正常血小板对HIT抗体的体外激活反应，并且是HIT血小板减少症的一个危险因素。
