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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3598-3602.
Prepublished online as a Blood First Edition Paper on August 17, 2004; DOI 10.1182/blood-2004-03-1107.


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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

{beta}2-glycoprotein I–dependent lupus anticoagulant highly correlates with thrombosis in the antiphospholipid syndrome

H. Bas de Laat, Ronald H.W.M. Derksen, Rolf T. Urbanus, Mark Roest, and Philip G. de Groot

From the Department of Haematology, University Medical Centre Utrecht, the Netherlands; the Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, the Netherlands; and the Department of Clinical Chemistry, University Medical Centre Utrecht, the Netherlands.

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.


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