HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY 2-glycoprotein I–dependent lupus anticoagulant highly correlates with thrombosis in the antiphospholipid syndrome

The antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies in plasma of patients with thromboembolic complications. A major problem in defining the syndrome is that serologic assays to detect antiphospholipid antibodies have a low specificity. We recently published a method that specifically detects lupus anticoagulant (LAC) caused by anti– 2-glycoprotein I antibodies. Here, we studied the clinical relevance of detecting 2-glycoprotein I– dependent LAC. Plasma samples were collected from 198 patients with autoimmune diseases. In those samples with a positive partial thromboplastin time– lupus anticoagulant (PTT-LA), a modified activated partial thromboplastin time (aPTT)–based LAC test was performed with cardiolipin as confirming agent. Twenty-five of 58 patients with an aPTTbased LAC were dependent on the presence of anti– 2-glycoprotein I antibodies. Presence of 2-glycoprotein I–dependent LAC was almost completely associated with a history of thromboembolic complications (odds ratio, 42.3; 95% confidence interval, 194.3-9.9). An increased frequency of thrombosis was not found in 33 patients with LAC independent of anti– 2-glycoprotein I antibodies (odds ratio, 1.6; 95% confidence interval, 3.9-0.8). The use of an LAC assay with cardiolipin as confirming agent strongly improves the detection of patients at risk of thrombosis. Our findings suggest that anti– 2glycoprotein I antibodies with LAC activity are antibodies that are responsible for the thromboembolic complications in the antiphospholipid syndrome. (Blood. 2004; 104:3598-3602)