Antiphospholipid antibody syndrome: new insights on thrombogenic mechanisms

The antiphospholipid antibody syndrome is a thrombophilic condition manifested by vascular thrombosis or recurrent pregnancy loss together with the presence of antibodies against anionic phospholipid protein complexes. These antibodies are detected by their reactivity to the anionic phospholipids (or protein phospholipid complexes) in solid-phase immunoassays or by their property of inhibiting phospholipid-dependent coagulation reactions (the "lupus anticoagulant" effect). The pathophysiologic mechanisms of this syndrome have remained obscure because of the apparent multiplicity of antigenic determinants recognized by the antibodies and also because of the many effects which have been described for them. This article reviews current concepts of the antiphospholipid disease process and evidence for the hypothesis that thrombosis in this syndrome is a result of the displacement of annexin-V, an anionic phospholipid-binding protein with potent anticoagulant activity, from phospholipid surfaces. The authors propose that under physiologic conditions, annexin-V plays a thromboregulatory role at the vascular-blood interface by shielding anionic phospholipids from complexation with coagulation proteins in circulating blood. Thrombosis in the antiphospholipid syndrome is due to disruption of the annexin shield by antiphospholipid (and cofactor) antibodies which results in the increased exposure of thrombogenic phospholipids. Accumulated data are consistent with the hypothesis that the disruption of annexin-V binding to anionic phospholipid surfaces plays an important thrombogenic role in the antiphospholipid syndrome.