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Published on: February 10, 2023
Autoantibodies against endothelial protein C receptor and the risk of a first deep vein thrombosis
A van Hylckama Vlieg1, R Montes, F R Rosendaal
1Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
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.
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