High-titer antiphospholipid antibodies, both the lupus anticoagulant (LA) and anticardiolipin antibody (aCL) are associated with a clinical syndrome that includes (1) venous thrombosis, usually deep venous thrombosis; (2) arterial thrombosis, including stroke, digital gangrene, or myocardial infarction; (3) idiopathic habitual abortion; and/or (4) thrombocytopenia. Patients with the antiphospholipid antibody syndrome (APS) may have no definable connective tissue disease (primary APS, or PAPS) or they may have systemic lupus erythematosus, undifferentiated connective tissue disease, another rheumatologic diagnosis, malignancy, or associated disease (secondary APS, or SAPS). Very few patients will have all four of the major criteria of the syndrome, but it is not unusual for a patient to have more than one. Of the minor criteria that characterize APS, livedo reticularis is one of the most common, and is often the first clue on physical examination to the presence of antiphospholipid antibodies. The laboratory definition of APS requires identification of one or both of the most clinically relevant antiphospholipid antibodies, LA or aCL. In the case of LA, coagulation tests are used rather than the measurement of an antibody titer to identify one of the actions of the antibody (blocking the formation of the prothrombin activator complex). Although the activated partial thromboplastin time (APTT) has been commonly employed as a screening procedure, the substrate used in most hospital laboratories has limited sensitivity in the detection of lupus anticoagulants. More sensitive tests are phospholipid-poor, including the modified Russell viper venom time (RVVT), kaolin clotting time (KCT), and platelet neutralization procedure (PNP). To differentiate the presence of LA from a factor deficiency in a patient with a prolonged clotting time, a 1:1 mixing procedure with normal plasma is performed. Anticardiolipin antibody is the prototype for a group of antibodies directed against negatively charged phospholipids, measured in solid phase ELISA assays. Although all isotypes have been found in patients with APS, high-titer IgG aCL is especially associated with thrombosis and/or pregnancy loss. In some cases, antiphospholipid antibodies identified in solid-phase assays may actually be directed against a complex of negatively charged phospholipid and β2-glycoprotein I, a naturally, occurring anticoagulant. Treatment of patients with antiphospholipid antibodies is not well defined. Patients with LA or aCL who have not had a past thrombotic event are not currently treated prophylactically. Patients who have a venous thrombotic event or an arterial thrombotic event (such as a stroke or myocardial infarction) are candidates for long-term anticoagulation with warfarin. Corticosteroids de not appear to be sufficient therapy to prevent future thrombotic events, but certainly can be used in patients with connective tissue disease to control other autoimmune-mediated organ damage. A daily baby aspirin (or other doses of aspirin) has been used for neurologic thrombotic events, but may not be adequate protection against subsequent thrombotic episodes. Because of the teratogenic potential of warfarin, other regimens have been investigated for recurrent pregnancy loss. The most widely used regimens have been either prednisone (either 20 mg or 40 mg daily) and a baby aspirin or subcutaneous heparin in varying doses. Higher doses of daily prednisone are associated with maternal morbidity (preeclampsia, gestational diabetes, and cataract) and fetal morbidity (preterm birth). The potential role of other therapies (plasmapheresis, intravenous gammaglobulin) in either thrombosis or pregnancy loss has not been adequately studied.
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