Autoantibodies against endothelial protein C receptor and the risk of a first deep vein thrombosis

Summary Background: 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. Objectives: 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. Results: 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. Conclusions: This study demonstrates that the presence of anti‐EPCR autoantibodies is a moderate risk factor for DVT in the general population.