Annexin V inhibits prothrombin activation and is able to prevent thrombus formation under normal venous and arterial blood flow conditions. Antibodies to annexin V have been identified in association with several pathological conditions, including systemic lupus erythematosus (SLE) with or without anti-phospholipid syndrome, recurrent spontaneous abortions and systemic sclerosis (SSc). These antibodies are suspected to exert a detrimental role and interfere with annexin V function. Thus, they have been associated with the occurrence of foetal loss and venous and/or arterial thrombosis in SLE patients, as well as digital ischemia in SSc patients. However, their true pathogenic role remains to be proven.