Pathogenesis of Antiphospholipid Syndrome

Abstract

The antiphospholipid syndrome (APS) is a prothrombotic disorder characterized by recurrent arterial/venous thrombosis and pregnancy complications in association with the persistent presence of antiphospholipid antibodies (aPL). The role of aPL in the development of APS manifestations is widely recognized, but the pathogenic mechanisms that lead to thrombosis are only partially understood. Evidence has shown that the dominant antigenic targets for aPL in APS are phospholipid-binding plasma proteins such as β2-glycoprotein I and prothrombin. Comprehensive research into the mechanisms implicated in aPL-mediated thrombosis has greatly advanced our knowledge of the pathophysiology of APS. aPL may affect the normal procoagulant and anticoagulant reactions occurring on cell membranes and may also interact with certain cells, altering the expression and production of procoagulant and proinflammatory substances. Furthermore, aPL may activate complement causing and perpetuating APS manifestations. The identification of various candidate cell receptors for aPL-cell interaction and the intracellular signaling pathways mediating pathogenic effects of aPL on different cell types have increased our understanding of the hypercoagulable state of APS.