CLINICAL SYNDROMES ASSOCIATED WITH LUPUS ANTICOAGULANTS

Recent evidence suggests that lupus anticoagulants are immunologically distinct from the anticardiolipin antibodies. Nevertheless, the associated clinical complications exhibited by the two groups of antibodies are similar. They have been shown to have a strong association with a history of arterial and venous thrombosis, thrombocytopenia and neurological disease in patients with SLE or lupus-like disorders. The association between antiphospholipid antibodies and recurrent fetal loss is suggested by the currently available data but is not firmly established. Patients with lupus and antiphospholipid antibodies and an established history of recurrent fetal wastage are at high risk for experiencing subsequent fetal loss, but it is not yet known whether the same is true for patients without a history of fetal loss. The association of thrombosis, neurological disease, thrombocytopenia, and fetal loss in patients with non-SLE disorders has not been as extensively studied. Only recently have investigators such as Ginsberg and colleagues begun to show in prospective studies that there may, in fact, be a statistically significant risk of thrombotic events in otherwise healthy individuals with antiphospholipid antibodies. Many of the diverse minor manifestations reported in individual patients, case series, or cross-sectional studies such as livedo reticularis, leg ulcers, and hemolytic anemia may, alternatively, be due to coincidence or chance. Efforts to elucidate the mechanisms of thrombosis in patients with antiphospholipid antibodies is an area of active research. Most efforts have been based on the effects of these antibodies on endothelial cell and platelet function as well as on the fibrinolytic system. In addition, it has recently been shown that binding of antiphospholipid antibodies to phospholipids requires the serum 'cofactor' beta2-glycoprotein I. In patients with SLE selected for the presence of the lupus anticoagulant, thrombosis, or fetal loss, Viard and associates found that 17 of 47 (36%) patients had anti-beta2-glycoprotein I antibodies. They were able to show, in their small retrospective study, that there was an association between the presence of these antibodies and anticardiolipin activity, lupus anticoagulant activity, and thrombotic events, but not with spontaneous abortion. Of patients with SLE and thrombosis (9 of 47) eight of nine were positive for anti-beta2-glycoprotein I antibodies, seven of nine were positive for anticardiolipin antibodies, and eight of nine were positive for the lupus anticoagulant. The known inhibitory effect of beta2-glycoprotein I on platelet aggregation, on platelet prothrombinase activity, and on the intrinsic pathway of coagulation supports the hypothesis that implicates beta2-glycoprotein I in the pathogenesis of unwanted thrombotic events. Beta2-glycoprotein I, it is envisioned, could bind to platelets and could then be the cellular epitope for antiphospholipid antibody binding, leading to platelet aggregation and subsequent thrombosis. Further investigations into the exact mechanisms involved are in progress. From the collective data now available regarding the clinical manifestations associated with antiphospholipid antibodies can be proposed the following guidelines regarding the evaluation of a patient with suspected risk for the presence of these antibodies. Firstly, given the variability of the tests available for the assay of individual antiphospholipid antibodies, it can be recommended that patients at risk be tested for both the lupus anticoagulant and anticardiolipin antibodies. Secondly, given the potential variability in the individual test results in a given patient over time, it is further recommended that patients with initially positive test results undergo repeat testing in the following 2 to 4 months. Antibody titer should also be noted given the possible increased association of high titers with clinical complications. The patient with persistently elevated lupus anticoagulant or anticardiolipin antibody can then be appropriately counseled regarding the risks of complications of the antiphospholipid syndrome. Actual treatment is still highly controversial and is not addressed in this review. Finally, it is hoped that further prospective studies will be undertaken to determine the prognostic value and the full clinical usefulness of the lupus anticoagulant, and other antiphospholipid antibodies.