A thrombin–cross‐reactive anticardiolipin antibody binds to and inhibits the anticoagulant function of activated protein C

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Abstract
Objective To test the hypotheses that some thrombin‐reactive anticardiolipin antibodies (aCL) may bind to protein C (PC) and/or activated PC (APC), and that some of the PC‐ and APC‐reactive aCL may inhibit PC activation and/or the function of APC. Methods We studied the reactivity of patient‐derived monoclonal aCL with PC and APC. We examined the effects of the reactive antibodies on PC activation and on the activity of APC in plasma coagulation. Results Five of 5 patient‐derived, thrombin‐reactive monoclonal aCL bound to PC and APC. In addition, 1 patient‐derived monoclonal antiprothrombin antibody (APT) that displayed aCL activity and reacted with thrombin also bound to PC and APC. Of these 6 PC‐ and APC‐reactive aCL/APT, all failed to inhibit PC activation, but 1 (CL15) shortened the plasma coagulation time in the presence of exogenous APC and thus inhibited the anticoagulant function of APC. Conclusion Most of the thrombin‐reactive aCL in patients with antiphospholipid syndrome may bind to PC and APC. Of the APC‐reactive aCL, some (like CL15) may inhibit the anticoagulant function of APC and are thus likely to be prothrombotic in the host.