ESSENTIALS OF DIAGNOSIS
Hypercoagulability; recurrent arterial or venous thromboses.
Thrombocytopenia is common.
Recurrent fetal loss.
Recurrent events are frequent; lifetime anticoagulation with warfarin is recommended.
The clinical features of primary antiphospholipid syndrome (APS) are venous or arterial occlusions or certain pregnancy complications. Laboratory criteria include the identification of at least one of the following three antiphospholipid antibodies: IgG or IgM anticardiolipin, IgG or IgM antibodies to beta-2-glycoprotein 1, and lupus anticoagulant. In less than 1% of patients with antiphospholipid antibodies, a potentially devastating syndrome known as the “catastrophic antiphospholipid syndrome” occurs, leading to diffuse thromboses, thrombotic microangiopathy, and multiorgan system failure. Catastrophic APS has a mortality rate approaching 50%.
Patients are often asymptomatic until suffering a thrombotic complication of this syndrome or a pregnancy loss. Thrombotic events may occur in either the arterial or venous circulations. Thus, deep venous thromboses, pulmonary emboli, and cerebrovascular accidents are typical clinical events. Budd-Chiari syndrome, cerebral sinus vein thrombosis, myocardial or digital infarctions, hemorrhagic infarction of the adrenal glands (due to adrenal vein thrombosis), and other thrombotic events also occur. Other symptoms and signs of APS include thrombocytopenia, mental status changes, livedo reticularis, skin ulcers, microangiopathic nephropathy, and cardiac valvular thickening or vegetations. Pregnancy losses include unexplained fetal death after 10 weeks’ gestation; one or more premature births before 34 weeks because of eclampsia, preeclampsia, or placental insufficiency; or three or more unexplained miscarriages before 10 weeks’ gestation.
Thrombocytopenia occurs in 22–42% of patients, and it is usually moderate (platelet counts above 50,000/mcL [50 × 109/L]). The presence of thrombocytopenia does not reduce the risk of thrombosis.
Three types of antiphospholipid antibodies are associated with this syndrome: (1) anti-cardiolipin antibodies, (2) antibodies to beta-2-glycoprotein, and (3) a “lupus anticoagulant” that prolongs certain phospholipid-dependent coagulation tests (see below). Antibodies to cardiolipin and to beta-2-glycoprotein are typically measured with enzyme immunoassays. Anti-cardiolipin antibodies can produce a biologic false-positive test for syphilis (ie, a positive rapid plasma reagin but negative specific anti-treponemal assay). In general, IgG anti-cardiolipin antibodies are believed to be more pathologic than IgM. In case-control studies, 3.1% of patients in the general population who experienced a venous thrombotic event (in the absence of cancer) tested positive for the lupus anticoagulant (versus 0.9% of controls, yielding an odds ratio of 3.6). For women younger than 50 years in whom stroke developed, the odds ratio for having the lupus anticoagulant is 43.1. Presence of the lupus anticoagulant is a stronger risk factor for thrombosis or pregnancy loss than is the presence of antibodies to either beta-2-glycoprotein 1 or anticardiolipin. A clue to the presence of a lupus anticoagulant, which may occur in individuals who do not have SLE, may be detected by a prolongation of the ...