ANTIPHOSPHOLIPID ANTIBODY SYNDROME - NEW INSIGHTS ON THROMBOGENIC MECHANISMS

The antiphospholipid antibody syndrome is a thrombophilic condition ma nifested by vascular thrombosis or recurrent pregnancy loss together w ith the presence of antibodies against anionic phospholipid protein co mplexes. These antibodies are detected by their reactivity to the anio nic phospholipids (or protein phospholipid complexes) in solid-phase i mmunoassays or by their property of inhibiting phospholipid-dependent coagulation reactions (the ''lupus anticoagulant'' effect). The pathop hysiologic mechanisms of this syndrome have remained obscure because o f the apparent multiplicity of antigenic determinants recognized by th e antibodies and also because of the many effects which have been desc ribed for them. This article reviews current concepts of the antiphosp holipid disease process and evidence for the hypothesis that thrombosi s in this syndrome is a result of the displacement of annexin-V, an an ionic phospholipid-binding protein with potent anticoagulant activity, from phospholipid surfaces. The authors propose that under physiologi c 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 anti phospholipid syndrome is due to disruption of the annexin shield by an tiphospholipid (and cofactor) antibodies which results in the increase d exposure of thrombogenic phospholipids. Accumulated data are consist ent with the hypothesis that the disruption of annexin-V binding to an ionic phospholipid surfaces plays an important thrombogenic role in th e antiphospholipid syndrome.