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

Objective. To test the hypothesis that some lupus anticoagulants are antipr othrombin 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 an tibody. It bound to prothrombin with low affinity, reacted with 3 phospholi pids (cardiolipin, phosphatidylethanolamine, and phosphatidylserine), and s howed lupus anticoagulant activity. Moreover, IS6 enhanced the binding of p rothrombin to damaged EC and shortened the EC-based plasma coagulation time s. Conclusion. These findings suggest that IS6 may promote coagulation in area s of damaged EC in the host, and thus contribute to thrombosis in patients with APS.