Antiphospholipid Syndrome: Thrombosis

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by vascular thrombosis (arterial and/or venous) and/or pregnancy morbidity in the persistent presence of antiphospholipid antibodies (aPL). The three clinically significant aPL antibodies are lupus anticoagulant (LA), anticardiolipin antibodies (aCL, IgG and IgM), and anti-beta2-glycoprotein I antibodies (anti-B2GPI, IgG and IgM). Despite the name 'lupus anticoagulant,' this antibody is actually prothrombotic in vivo while prolonging phospholipid-dependent coagulation assays in vitro (aPTT prolongation that does not correct with mixing study). The pathogenic mechanism involves aPL antibodies binding to beta2-glycoprotein I on endothelial cell surfaces, activating endothelial cells, monocytes, and platelets, upregulating tissue factor expression, inhibiting protein C activation, and disrupting annexin A5 anticoagulant shield on trophoblasts and endothelium. This creates a prothrombotic state affecting both arterial and venous circulations. In pregnancy, aPL antibodies impair trophoblast invasion, activate complement on the placental surface, and cause placental insufficiency leading to recurrent miscarriage, fetal growth restriction, preeclampsia, and stillbirth. Catastrophic APS (CAPS) is a rare, life-threatening variant with simultaneous multi-organ thrombosis developing over days, affecting kidneys, lungs, brain, and heart with >50% mortality without treatment.