Antiphospholipid antibodies (aPL)

Antiphospholipid antibodies (aPL) are a heterogeneous group of pathogenic autoantibodies directed against phospholipid-binding proteins, most notably Beta-2-glycoprotein I (B2GPI) and prothrombin (Hopkins Lupus Center, 2024; NIH, 2023). These antibodies are the hallmark of Antiphospholipid Syndrome (APS), a systemic autoimmune disorder characterized by recurrent arterial or venous thrombosis and pregnancy-related complications such as miscarriage or preeclampsia (StatPearls, 2024; HSS, 2017). Mechanistically, aPL induce a prothrombotic state by activating endothelial cells, platelets, and monocytes, and by interfering with natural anticoagulant pathways like the annexin A5 shield and the protein C system (Blood, 2010; Medscape, 2024). They also trigger the complement cascade, which contributes to tissue injury and fetal loss (Medscape, 2024). The presence of these antibodies leads to a "two-hit" model of thrombosis, where the antibodies create a prothrombotic environment that requires an additional trigger to cause a clinical event (Medscape, 2024). Therapeutic management primarily involves long-term anticoagulation with vitamin K antagonists or heparin to prevent clots (StatPearls, 2024; BMJ, 2019). Emerging targeted therapies aim to reduce aPL production via B-cell depletion (e.g., rituximab) or to block downstream pathogenic pathways using complement inhibitors (e.g., eculizumab) and mTOR inhibitors (e.g., sirolimus) (NIH, 2023; Blood, 2007). Hydroxychloroquine is also utilized for its ability to protect the annexin A5 anticoagulant shield from aPL-mediated disruption (Blood, 2010).

Other names

Anti-phospholipid antibodiesLupus anticoagulantAnti-cardiolipin antibodiesAnti-beta-2-glycoprotein I antibodiesAntiphospholipid autoantibodies

Inhibition of autoantibody production, neutralization of downstream complement activation, protection of anticoagulant shields, and systemic anticoagulation.