ESSENTIALS OF DIAGNOSIS
Hypercoagulability; recurrent arterial or venous thromboses.
Thrombocytopenia is common.
Recurrent fetal loss.
Recurrent events are common; lifetime anticoagulation with warfarin is recommended.
Primary antiphospholipid syndrome (APS) is diagnosed in patients who have venous or arterial occlusions or pregnancy complications (ie, three or more first-trimester miscarriages, unexplained fetal death, and premature birth before 34 weeks of gestation attributable to severe preeclampsia, eclampsia, or placental insufficiency) with persistent (12 weeks or longer), high-titer, diagnostic antiphospholipid antibodies but no other features of SLE (see Chapter 19-18). Diagnostic antiphospholipid antibodies are IgG or IgM anticardiolipin, or 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.
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 among patients with the APS. 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. 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. A variety of other symptoms and signs are often attributed to the APS, including thrombocytopenia, mental status changes, livedo reticularis, skin ulcers, microangiopathic nephropathy, and cardiac valvular dysfunction—typically mitral regurgitation due to Libman-Sacks endocarditis. Livedo racemosa is strongly associated with the subset of patients with APS in whom arterial ischemic events develop. Pregnancy losses that are associated with APS include unexplained fetal death after the first trimester, one or more premature births before 34 weeks because of eclampsia or preeclampsia, or three or more unexplained miscarriages during the first trimester.
As noted in the discussion of SLE, three types of antiphospholipid antibody 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. Presence of the lupus anticoagulant is a stronger risk factor for thrombosis or pregnancy loss than is ...