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-beta(2)-glycoprotein I
antibodies. Here, we studied the clinical relevance of detecting beta(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 aPTT-based LAC were dependent on the presence of anti-beta(2)-glycoprotein I
antibodies. Presence of beta(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-beta(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-beta(2)-glycoprotein I
antibodies with LAC activity are
antibodies that are responsible for the thromboembolic complications in the
antiphospholipid syndrome.