Understanding antiphospholipid syndrome clinical phenotypes with the guidance of antiphospholipid antibody-related...

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis, microvascular disease, pregnancy morbidity, or non-thrombotic manifestations in patients with antiphospholipid antibodies. The mechanistic differentiation of these clinical phenotypes has diagnostic and therapeutic implications. Across APS phenotypes, a shared set of effector mechanisms are: a) endothelial activation and dysfunction; b) platelet, monocyte, and neutrophil activation; c) complement activation; and d) downstream coagulation system activation. Taken together, these shared mechanisms provide a unifying framework for understanding how APS produces an immunothrombotic environment as well as distinct, yet overlapping, clinical domains. In this review article, we apply this framework to: a) macrovascular (thrombotic) APS; b) microvascular APS; c) obstetric APS; d) non-thrombotic aPL manifestations; and d) catastrophic APS, highlighting phenotype-specific clinical and mechanistic nuances while emphasizing convergent pathways.