Recent insights into antiphospholipid antibody-mediated thrombosis

The clinically relevant antiphospholipid antibodies (APA) include anticardi olipin antibodies and lupus anticoagulant. Most autoimmune APA require the presence of a cofactor for phospholipid binding, and the growing list of ca ndidate cofactors has prompted redefinition of APA to 'antiphospholipid pro tein antibodies'. Current evidence favours beta(2)-glycoprotein I (beta(2)G PI) and prothrombin as the primary antigens for anticardiolipin antibodies and lupus anticoagulant respectively. Patients with APA show a predispositi on for venous and arterial thromboembolism, recurrent fetal loss, thrombocy topenia and a number of neurological syndromes and miscellaneous conditions . The association between APA and thrombosis has been well documented, but a definite mechanism remains to be clarified. Proposed mechanisms have incl uded disruption of endothelial regulatory processes, impairment of fibrinol ysis. augmented platelet activation and/or adhesion, inhibition of antithro mbin activity and negation of the anticoagulant effects of beta(2)GPI and a nnexin V. In this review we describe recent insights into the role of beta( 2)GPI as a natural anticoagulant, the procoagulant effects of APA on the Pr otein C system, the interactions between APA and prothrombin resulting in a ugmentation of thrombin generation, and cellular expression of Tissue Facto r in patients with APA. Cellular immunity to beta(2)GPI is also discussed. Elucidation of these pathophysiological mechanisms may shed further light o n the association between APA and thrombosis.