Anti-prothrombin antibodies cause thrombosis in a novel qualitative ex-vivo animal model

Abstract

Anti-prothrombin antibodies (aPT) are associated with thrombotic manifestations, and their association with reproductive failure is debatable. The aim of this study was to examine whether aPT could induce thrombosis and other clinical manifestations of the anti-phospholipidsyndrome (APS). Mice were immunized with either prothrombin, b2-glycoprotein-I (b2GPI), or b2GPI followed by prothrombin. The presence of clinical manifestation of APS, including thrombocytopenia, lupus anticoagulant and fetal resorption rates, was evaluated in all mice groups compared with nonimmunized mice. Thrombosis was studied in a novel ex-vivo model in which the aorta was sutured for 1min and the presence or absence of visible thrombus was qualitatively evaluated. Immunized mice developed high autoantibodylevels directed towards their immunizing autoantigens.The groups immunized with b2GPI or b2GPI=prothrombin, but not with prothrombin alone, developed prolonged aPTT, thrombocytopeniaand increased fetal resorption rate. All prothrombin-immunized mice as well as most b2GPI=prothrombin-immunized mice developed visible thrombus within the aorta. Some b2GPI immunized mice developed very mild thrombus. None of the CFA=PBS-injected or the nonimmunized mice developed such thrombus. Active immunization with prothrombin or b2GPI=prothrombin is associated with prothromboticactivity of blood in an ex-vivo model. This is the first direct evidence for thrombus induction by aPT.