Fig. 2

Thrombotic mechanisms mediated by aPL. Vascular dysfunction, inflammatory cell infiltration, and complement deposition all play a critical role in the pathogenesis of APS, as depicted in the illustration. First, the presence of aPL initiates clotting, which in turn activates another procoagulant state, the so-called “second hit”, to induce complete clot formation, which appears to necessitate complement activation in vivo. When immunogenic phospholipid-binding proteins such as β₂GPI and prothrombin are cross-linked by aPL, cellular activation can be evoked. aPL increases endothelial leukocyte adhesion, cytokine secretion, and PGE₂ synthesis by upregulating tissue factor expression on endothelial cells and monocytes. Excessive endosomal reactive oxygen species generation in monocytes, the neutrophil release of prothrombotic extracellular traps (NETosis), and complement activation on the surface of endothelium and other cell types significantly intensify inflammation and thrombosis formation. aPL, antiphospholipid autoantibodies; β₂GPI, β₂ glycoprotein I; LACA, Lupus anticoagulant antibody; ACLA, anticardiolipin antibody; PGE₂, prostaglandin E₂; PBP, phospholipid-binding protein