An IgG antiprothrombin antibody enhances prothrombin binding to damaged endothelial cells and shortens plasma coagulation times

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Abstract
Objective To test the hypothesis that some lupus anticoagulants are antiprothrombin antibodies, and that such antibodies enhance prothrombin binding to endothelial cells (EC) and thus promote clotting on the cell surface. Methods We generated a monoclonal antiprothrombin antibody (designated IS6) from a patient with primary antiphospholipid syndrome (APS). The antibody was analyzed for its binding properties, lupus anticoagulant activity, and pathophysiologic activity, using an EC‐based plasma coagulation assay. Results IS6 is the first patient‐derived monoclonal IgG antiprothrombin antibody. It bound to prothrombin with low affinity, reacted with 3 phospholipids (cardiolipin, phosphatidylethanolamine, and phosphatidylserine), and showed lupus anticoagulant activity. Moreover, IS6 enhanced the binding of prothrombin to damaged EC and shortened the EC‐based plasma coagulation times. Conclusion These findings suggest that IS6 may promote coagulation in areas of damaged EC in the host, and thus contribute to thrombosis in patients with APS.