van Hylckama Vlieg A, Montes R, Rosendaal F R, Hermida J
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
J Thromb Haemost. 2007 Jul;5(7):1449-54. doi: 10.1111/j.1538-7836.2007.02582.x. Epub 2007 Apr 16.
The endothelial protein C receptor (EPCR) binds protein C and enhances its activation. Anti-EPCR autoantibodies are found in patients with antiphospholipid syndrome and may explain the increased risk of thrombosis in these patients. Anti-EPCR autoantibodies have been associated with fetal death and myocardial infarction in young women.
To determine whether anti-EPCR autoantibodies are associated with deep vein thrombosis (DVT).
PATIENTS/METHODS: We measured plasma anti-EPCR autoantibody levels in the Leiden Thrombophilia Study (LETS), a population-based case-control study consisting of 474 patients with a first DVT and 474 control subjects.
The estimated risk of DVT was increased approximately 2-fold in the presence of elevated IgA, IgG or IgM anti-EPCR autoantibodies (i.e. levels above the 90th percentile as measured in the control subjects). The risk conferred by anti-EPCR increased in a dose-dependent manner for IgA and IgG. When anti-EPCR autoantibodies were considered in the co-presence of lupus anticoagulant (LAC) the odds ratio (OR) was 6.1 [95% CI 1.3-27.9]. Anti-EPCR without LAC remained associated with DVT (OR 1.6; 95% CI 1.2-2.1). Anti-EPCR autoantibodies were associated with high levels of D-dimer and soluble EPCR in controls, suggestive of a prothrombotic status induced by the autoantibodies.
This study demonstrates that the presence of anti-EPCR autoantibodies is a moderate risk factor for DVT in the general population.
内皮细胞蛋白C受体（EPCR）可结合蛋白C并增强其活化作用。抗磷脂综合征患者体内可检测到抗EPCR自身抗体，这可能解释了这些患者血栓形成风险增加的原因。抗EPCR自身抗体与年轻女性的胎儿死亡和心肌梗死有关。
确定抗EPCR自身抗体是否与深静脉血栓形成（DVT）有关。
患者/方法：我们在莱顿血栓形成倾向研究（LETS）中检测了血浆抗EPCR自身抗体水平，该研究是一项基于人群的病例对照研究，包括474例首发DVT患者和474例对照者。
在IgA、IgG或IgM抗EPCR自身抗体水平升高（即高于对照者检测的第90百分位数）的情况下，DVT的估计风险增加约2倍。IgA和IgG的抗EPCR风险呈剂量依赖性增加。当同时存在狼疮抗凝物（LAC）时，抗EPCR自身抗体的比值比（OR）为6.1 [95%可信区间（CI）1.3 - 27.9]。无LAC的抗EPCR自身抗体仍与DVT相关（OR 1.6；95% CI 1.2 - 2.1）。抗EPCR自身抗体与对照者中高水平的D - 二聚体和可溶性EPCR相关，提示自身抗体诱导了血栓前状态。
本研究表明，抗EPCR自身抗体的存在是普通人群发生DVT的中度危险因素。
