22-09: Antiphospholipid Syndrome

ESSENTIALS OF DIAGNOSIS

GENERAL CONSIDERATIONS

Antiphospholipid syndrome (APS) can occur alone or in association with other autoimmune diseases such as SLE. The clinical features of APS are venous or arterial occlusions or certain pregnancy complications. Patients have at least one of the following three antiphospholipid antibodies: anticardiolipin antibodies, antibodies to beta-2-glycoprotein 1, and lupus anticoagulant.

Catastrophic antiphospholipid syndrome occurs in less than 1% of patients with antiphospholipid antibodies. This potentially devastating syndrome leads to diffuse thromboses, thrombotic microangiopathy, and multiorgan system failure. Catastrophic APS has a mortality rate approaching 50%.

CLINICAL FINDINGS

A. Symptoms and Signs

Patients are often asymptomatic until suffering a thrombotic complication or a pregnancy loss. Thrombotic events may occur in either the arterial or venous circulations. 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, pulmonary hemorrhage, and cardiac valvular thickening or vegetations. Obstetric manifestations include 3 or more consecutive pregnancy losses before 16 weeks’ gestation, fetal deaths between 16 and 33 weeks’ gestation in the absence of preeclampsia or placental insufficiency, or severe preeclampsia or placental insufficiency occurring before 34 weeks with or without fetal death.

The American College of Rheumatology and the European League Against Rheumatism have revised the classification of antiphospholipid syndrome by assigning scores to the results of assay tests and clinical findings. The classification criteria require a positive aPL test (a lupus anticoagulant, moderate to high titers of anticardiolipin or anti–beta-2-glycoprotein-I antibodies) within 3 years of clinical criterion which are weighted by presence, absence, or severity of the following: venous embolism or venous or arterial thrombosis; microvascular conditions, such as livedo racemosa, livedoid vasculopathy, aPL nephropathy, pulmonary or adrenal hemorrhage; obstetric complications, such as fetal death or preeclampsia with severe features; cardiac valve thickening or vegetations; or thrombocytopenia.

B. Laboratory Findings

Thrombocytopenia occurs in 22–42% of patients and 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) IgG or IgM anti-cardiolipin antibodies, (2) IgG or IgM antibodies to beta-2-glycoprotein, and (3) “lupus anticoagulant” that prolongs certain phospholipid-dependent coagulation tests (see below). 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 ...