Revisiting antiphospholipid syndrome: A thrombo-inflammatory disorder beyond clotting

The dysregulation of protective immunothrombosis is termed thrombo-inflammation. Antiphospholipid syndrome (APS) is an antibody mediated autoimmune, inflammatory and prothrombotic disease. APS is an archetypal disease for thrombo-inflammation, in which a proinflammatory/prothrombotic state is caused by antiphospholipid antibodies (aPL). These antibodies directly or indirectly exert effects on monocytes and neutrophils, as well as platelets and endothelium, through binding of phospholipid binding proteins. In addition, aPL are linked with activation of coagulation and complement, leading to thrombosis. Although APS is an autoimmune antibody-mediated prothrombotic disease, its main treatment strategy at present is anticoagulation. Anticoagulation does not modulate endothelial cells or inflammation. This could explain the high risk of recurrent thrombosis, despite patients being on adequate anticoagulation. This review examines endothelial dysfunction and thrombo-inflammation in thrombotic APS as understanding the role of thrombo-inflammation in the pathogenesis of APS may help to develop new treatments or repurpose existing treatments.