beta2-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-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.
de Laat
H Bas
HB
Department of Haematology, G03.647, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands.
Derksen
Ronald H W M
RH
Urbanus
Rolf T
RT
Roest
Mark
M
de Groot
Philip G
PG
D000328:Adult; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000150:complications*; D001323:Autoantibodies / Q000097:blood / Q000502:physiology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D008297:Male; D016017:Odds Ratio; D010314:Partial Thromboplastin Time; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013927:Thrombosis / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D006023:Glycoproteins; D016682:Lupus Coagulation Inhibitor; D053482:beta 2-Glycoprotein I