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Factor V Leiden, Prothrombin Gene Mutation, and Thrombosis Risk in Patients with Antiphospholipid Antibodies
NIKHIL CHOPRA, SHARON KOREN, WENDA L. GREER, PAUL R. FORTIN, JOYCE RAUCH, ISABELLE FORTIN, JEAN-LUC SENÉCAL, PETER DOCHERTY, and JOHN G. HANLY
ABSTRACT.
Methods. One hundred fifty-seven patients with aPL antibodies were studied. The occurrence of venous and arterial thrombotic events since the time of antibody detection was determined retrospectively, using appropriate clinical and diagnostic criteria. Clinical risk factors for thrombosis were documented and included hypertension, hyperlipidemia, cigarette smoking, diabetes, positive family history, use of oral contraceptive, pregnancy, trauma, hospitalization, varicose veins, and malignancy. Genomic DNA was extracted from blood cells for determination of factor V Leiden mutation G1691 ® A and prothrombin mutation G20210 ® A by polymerase chain reaction and restriction fragment length polymorphism analysis. Results. Of 157 patients, 69 had a history of thrombosis (venous 37, arterial 32); 147 (94%) patients had anticardiolipin (aCL) antibodies; 69 (45%) had lupus anticoagulant (LAC). The prevalence of factor V Leiden in patients with thrombosis was 13% compared to 4.6% in patients without thrombosis (OR 3.11, CI 0.92-10.6). In patients with aCL antibodies, 15% of patients with arterial thrombosis had factor V mutation compared to 3.5% of patients without thrombosis (OR 4.9, CI 1.2-19.3). The prothrombin gene mutation was identified in 5 patients, none of whom had thrombosis. Stepwise logistic regression analysis indicated that LAC (p = 0.005), male sex (p = 0.04), and hypertension (p = 0.03) were the strongest risk factors for developing thrombosis and that no additional risk was conferred by factor V Leiden (p = 0.13) and prothrombin gene mutation. Conclusion. Although the prevalence of factor V Leiden is modestly increased in patients with autoimmune aPL antibodies and thrombosis, these results suggest that its detection does not significantly increase the risk of a thrombotic event, once other clinical risk factors have been considered. Prothrombin gene mutation is not associated with thrombosis in patients with aPL antibodies. (J Rheumatol 2002;29:1683-8) Key Indexing Terms:
ANTIPHOSPHOLIPID ANTIBODIES
From the Division of Rheumatology, Dalhousie University, Halifax, Nova Scotia; Division of Rheumatology, McGill University, Montreal, Quebec; Division of Rheumatology, University of Toronto, Toronto, Ontario; and Division of Rheumatology, Université de Montréal, Montreal, Quebec, Canada. Supported in part by grants from the Canadian Institutes of Health Research (Dr. Rauch), The Arthritis Society (Dr. Rauch, Dr. Fortin), Lupus Quebec (Dr. Fortin), and the Queen Elizabeth II Health Sciences Centre (Dr. Chopra, Dr. Hanly). Dr. Fortin is a Senior Research Scholar of The Arthritis Society and the Director of Clinical Research, Arthritis Center of Excellence, University of Toronto. N. Chopra, MD, FRCPC, Rheumatology Fellow; W.L. Greer, PhD, FCCMG, Professor of Pathology; P. Docherty, MD, FRCPC, Rheumatologist; J.G. Hanly, MD, MRCPI, FRCPC, Professor of Medicine, Dalhousie University; S. Koren, MD, FRCPC, Rheumatology Fellow; J. Rauch, PhD, Associate Professor of Medicine, McGill University; P.R. Fortin, MD, MPH, FRCPC, Associate Professor of Medicine, University of Toronto; I. Fortin, MD, Rheumatology Fellow; J-L. Senecal, MD, FRCPC, Professor of Medicine, Université de Montréal. Address reprint requests to Dr. J.G. Hanly, Division of Rheumatology, Department of Medicine, Suite 310, Bethune Building, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada B2H 2Y9. E-mail: jhanly@is.dal.ca Submitted September 10, 2001; revision accepted January 15, 2002. |