The Paradox of Lupus Anticoagulant

Abstract

A unique coagulation inhibitor prolonging whole blood clotting time was described more than 50 years ago in two patients with systemic lupus erythematosus (SLE). The immunoglobulin nature of the inhibitor and its interaction with anionic phospholipids (aPL) were then demonstrated, and the term “lupus anticoagulant” (LAC) was coined to describe this laboratory finding. It soon became apparent that LAC was a misnomer as it is often found in plasma from patients with clinical conditions other than SLE and is associated with thromboembolic events that may occur in otherwise healthy individuals. The frequently associated lupus anticoagulant with SLE is not restricted to these subjects, and, paradoxically, despite causing prolongation of clotting times in vitro, it is associated with a pronounced tendency to thrombosis. Individuals with LAC have circulating autoantibodies that inhibit blood coagulation. The autoantibodies are of the IgG or IgM isotype and are mainly directed against two phospholipid (PL)-binding plasma proteins, β2-glycoprotein I (β2GPI) and prothrombin. The presence of such inhibitors represents a well-recognized risk factor for venous and arterial thromboembolism, as well as pregnancy loss. The presence of LAC in a subject with previous documented thromboembolism, or a history of pregnancy loss, defines anti-PL syndrome (APS). Laboratory diagnosis of LAC is thus of particular importance, as it assigns patients with a common event (thrombosis) to a group with a high risk for recurrence, which is a prerequisite for long-term oral anticoagulant treatment.