Antiphospholipid antibody-mediated disruption of the annexin-V antithrombotic shield: A thrombogenic mechanism for the antiphospholipid syndrome

The mechanism(s) for thrombosis and pregnancy losses in the anti-phospholipid antibody syndrome have not yet been established. Annexin-V is an anionic phospholipid-binding protein with potent anticoagulant activity. The protein has been shown to be necessary for the maintenance of placental integrity and may play a thromboregulatory role at the maternal-fetal interface. There, it assembles over the apical surfaces of the placental villi and shields the underlying anionic phospholipids from availability for complexation with coagulation proteins. We have proposed that thrombosis and pregnancy loss in the antiphospholipid syndrome may be due to the disruption of the annexin-V shield by antiphospholipid (and co-factor) antibodies. The data accumulated from tissue immunohistochemistry, trophoblast and endothelial cell culture studies, coagulation studies using non-cellular phospholipids, and competition studies on artificial phospholipid bilayer are consistent with this hypothesis. (C) 2000 Academic Press.