Anti-β2-glycoprotein

Anti-β2-glycoprotein I (anti-β2GPI) antibodies are one of the three main laboratory criteria (along with lupus anticoagulant and anticardiolipin antibodies) used to diagnose antiphospholipid syndrome (APS), an autoimmune hypercoagulable disorder. β2-glycoprotein I is a plasma apolipoprotein that binds anionic phospholipids on cell membranes (e.g., platelets, endothelial cells) and has natural anticoagulant properties by inhibiting the intrinsic coagulation pathway and interfering with protein C activation. When autoantibodies bind β2GPI complexed with phospholipids, they disrupt the protein's normal anticoagulant function, activate endothelial cells and platelets, and promote a prothrombotic, pro-inflammatory state, leading to arterial/venous thrombosis, recurrent miscarriages (especially after 10 weeks gestation), and thrombocytopenia.

Clinically, APS can be primary or secondary (often associated with SLE). Diagnosis requires both clinical criteria (vascular thrombosis or pregnancy morbidity) and laboratory criteria (positive lupus anticoagulant, anticardiolipin IgG/IgM, or anti-β2GPI IgG/IgM on two occasions at least 12 weeks apart). Anti-β2GPI antibodies cause a paradoxical phenomenon: in vitro they prolong clotting tests (like PTT) by interfering with phospholipid-dependent coagulation assays, yet in vivo they promote thrombosis. This is tested via mixing studies, which fail to correct the prolonged PTT (distinguishing it from a factor deficiency).

Management involves long-term anticoagulation (typically warfarin, as DOACs are less effective in APS) for those with thrombotic events, and low-dose aspirin ± heparin during pregnancy to reduce miscarriage risk. Catastrophic APS is a rare but life-threatening variant with multiorgan thrombosis.