The Lupus Anticoagulant

Lupus-like anticoagulant (LLAC) is the term used to identify an acquired inhibitor (1) of blood coagulation, first described by Conley and Hartmann in patients with systemic lupus erythematosus (SLE) (2). A circulating “lupus-like” anticoagulant has been detected in 5-10% of all SLE patients. A lupus anticoagulant is also found in other diseases including immunologic, oncologic, gynecologic, and neurologic disorders (3-12). In autoimmune diseases a lupus anticoagulant may occur in families, suggesting a genetic predisposition (13-15). Methods now available can distinguish between lupus anticoagulant and other inhibitors of coagulation (i.e., agonist factor VIII, IX, X, XI, and XII) occurring in SLE (16-19) and, more generally, in autoimmune diseases. In fact, in mixtures of LLAC plasma and normal plasma an immediate inhibition can be observed which is not increased by prolonging the incubation period, in contrast to the gradual time-dependent inhibition that occurs in patients with other types of coagulation inhibitors. Phospholipid and Lupus Anticoagulant Interaction. Only in the last few years have significant advances been made in our understanding of the lupus anticoagulant mechanism of action. The thromboplastin generation test using diluted plasma or serum from a patient with a “lupus anticoagulant” is normal, suggesting that the lupus inhibitor does not interfere with the generation of intrinsic prothrombin (1, 20-22). However, the abnormality can be revealed when the patient's plasma is used, instead of normal plasma, as source of prothrombin and fibrinogen (1, 20, 22). These findings suggest that lupus anticoagulant interferes with the activation of prothrombin, acting at the junction between intrinsic and extrinsic coagulation pathways. In other words, the anticoagulant inhibits the “prothrombin activator complex” (factor Xa, factor V, calcium, and phospholipids) and, more particularly, seems to be directed against the phospholipid fraction of the complex (3, 4, 23).