The antiphospholipid antibody syndrome: A riddle wrapped in a mystery inside an enigma

Abstract

The antiphospholipid antibody syndrome (APS) is the association of certain clinical features with the presence of antiphospholipid antibodies (APA) in the serum or plasma of affected individuals. APS may be primary or secondary to another disease, typically autoimmune diseases such as systemic lupus erythematosus (SLE). The prototypic clinical features are thrombotic events (venous and arterial) and pregnancy morbidity (recurrent fetal loss, severe preeclampsia, eclampsia, and multiple spontaneous abortions). The term antiphospholipid antibody is a misnomer since it now appears that APA are actually directed against protein phospholipid complexes. APA may also occur secondary to infections however these APA seem to be directed at phopsholipid only and are transient. Particular phospholipid-binding proteins associated with APS include beta 2-glycoprotein I (B2GPI), prothrombin, and annexin V. A recent International Consensus Statement defines Definite APS as the presence of certain clinical findings (either a thrombotic event and/or pregnancy morbidity) and the presence and persistence of laboratory evidence of APA [either the lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACL)]. Other clinical features associated with APS include thrombocytopenia, various skin conditions, cardiac valvular diseases, and diverse neurological conditions as outlined in the main text. These other features may be part of APS but require further evidence to establish their pathological and clinical validity. Other laboratory tests of interest include anti-B2GPI, antiprothrombin, and antiphosphatidylserine antibodies. The diagnostic and clinical importance of these additional laboratory tests remains to be determined. APA are estimated to be present in up to 5% of the general population, with the prevalence increasing with age. APA are estimated to be present in 12% or more of patients with thrombosis. ACL are present in 12 to 30% of patients with SLE and LA are present in 15 to 34% of patients with SLE. There is often concordance between LA and ACL however this is not always true. APA (both ACL and LA) are associated with thromboembolic events. Venous thrombosis is more common than arterial thrombosis and a minority of patients have both. LA is more strongly associated with thrombosis than ACL. The estimated yearly incidence of thrombosis in individuals with APA is 1% for those with no history of thrombosis, 4% for those with SLE, and 6% for those with high titer immunoglobulin G (IgG) ACL. The presence of LA, and possibly of medium to high titers of IgG ACL, help identify patients at risk for thrombosis.