Pathogenesis of antiphospholipid antibody syndrome

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia characterized by venous or arterial thrombosis, and/or pregnancy loss or complications in the presence of persistently positive antiphospholipid antibodies (aPLs). These aPLs are a heterogeneous family of autoantibodies that bind various phospholipids (PLs) (principally cardiolipin) and PL-binding serum proteins, with the most important of these being β₂-glycoprotein I (β₂-GPI). The aPLs that are currently used in clinical practice to identify patients with APS tests include the detection of anticardiolipin antibodies and/or anti-β₂-GPI antibodies by enzyme-linked immunosorbent assay (ELISA) and/or positive lupus anticoagulant (LA) assay by prolongation of in vitro PL-dependent clotting assays, which can be corrected by the addition of excess PL. The development of various aPL tests and evidence that aPLs have wide-ranging proinflammatory and procoagulant effects on target cells, complement factors, and regulators of the coagulation cascade to promote vascular thrombosis and/or pregnancy morbidity will be reviewed in this chapter.