The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by the main clinical features of venous and/or arterial thrombosis (intravascular blood clotting), thrombocytopenia, recurrent fetal loss, and moderate-to-high titers of antiphospholipid (aPL) antibodies, lupus anticoagulant, anti-cardiolipin antibodies, and anti-beta-2-glycoprotein I antibodies (refs 1-2). aPL antibodies are autoantibodies that react with negatively-charged phospholipids such as cardiolipin. They are often found in the sera of patients with systemic lupus erythematosus and related diseases and are typical for the development of secondary APS. The presence of antiphospholipid antibodies in patients with no other autoimmune disease is characteristic of primary APS. Anti-cardiolipin antibodies are found in 80-90% of patients with APS. However, the presence of anti-cardiolipin antibodies are not specific to APS, because these antibodies may be detected in other autoimmune diseases, following administration of certain drugs, and in the aftermath of infectious disease (e.g., hepatitis C, syphilis, and infectious mononucleosis). Beta-2-glycoprotein I, also known as apolipoprotein H, inhibits the intrinsic coagulation pathway and is involved in the regulation of blood coagulation. Beta-2-glycoprotein I has been shown to be the primary autoantigen for anti-cardiolipin antibodies. Antibodies to beta-2-glycoprotein I are more specific to APS than anti-cardiolipin antibodies. Due to the heterogenous nature of aPL antibodies, combined measurements of anti-cardiolipin and anti-beta-2-glycoprotein I antibodies may provide better sensitivity than either assay alone.The criteria for defining APS as described by the Miyakis/Sapporo criteria (International Consensus Statement on an Update of the Classification Criteria for Definite Antiphospholipid Syndrome, Journal of Thrombosis and Hemostasis 2006; 4:295-306) are as follows:Clinical criteria:1. Vascular thrombosis One or more clinical episodes of arterial, venous or small vessel thrombosis2. Pregnancy morbidity (a) One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation (b) One or more pre-term births of a morphologically normal neonate before the 34th week of gestation because of: (i) eclampsia or severe pre-eclampsia or (ii) recognized features of placental insufficiency (c) Three or more unexplained consecutive spontaneous miscarriages before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excludedLaboratory criteria:1. Lupus anticoagulant present in plasma, on two or more occasions at least 12 weeks apart2. Anticardiolipin antibody of immunoglobulin IgG and/or IgM isotype in serum or plasma, present in medium or high titer (i.e. >40GPL units or MPL units, or > the 99th percentile), on two or more occasions, at least 12 weeks apart3. Anti-beta-2-glycoprotein I antibody of IgG and/or IgM isotype in serum or plasma (in titer >the 99th percentile), present on two or more occasions at least 12 weeks apartAPS is present if at least one of the clinical criteria and one of the laboratory criteria above are met.The presence of IgM antibodies to cardiolipin or beta-2-glycoprotein I at levels greater than 99th percentile is part of the SLICC (Systemic Lupus International Collaborating Clinics) Classification Criteria for Systemic Lupus Erythematosus immunologic criteria (ref. 3).References:1. International Consensus Statement on an Update of the Classification Criteria for Definite Antiphospholipid Syndrome, Journal of Thrombosis and Hemostasis 2006; 4:295-306.2. Devreese K and Hoylaerts M. Clinical Chemistry 2010; 56:930-940.3. Petri M et al. Arthritis and Rheumatism 2012; 64(8):2677-2686.