A Prospective Study of Asymptomatic Carriers of the Factor V Leiden Mutation To Determine the Incidence of Venous Thromboembolism
- Saskia Middeldorp, MD;
- Johan R. Meinardi, MD;
- Maria M.W. Koopman, MD;
- Elisabeth C.M. van Pampus, MD;
- Karly Hamulyák, MD;
- Jan van der Meer, MD;
- Martin H. Prins, MD; and
- Harry R. Büller, MD
- From Academic Medical Center, Amsterdam; University Hospital Groningen, Groningen; and University Hospital of Maastricht, Maastricht, the Netherlands.
Abstract
Background: The factor V Leiden mutation is a common genetic defect associated with an increased risk for venous thromboembolism. The clinical implications for asymptomatic carriers of this mutation and, consequently, the usefulness of screening families in which a proband has both the mutation and venous thromboembolism are unclear.
Objective: To determine the incidence of venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation.
Design: Prospective cohort study.
Setting: University hospitals in the Netherlands.
Participants: 470 asymptomatic carriers of the factor V Leiden mutation (234 men, 236 women; mean age, 43 years [range, 15 to 88 years]), 12 of whom were homozygous. Carriers were identified by screening the first-degree relatives (>15 years of age) of 247 symptomatic probands.
Measurements: Objectively diagnosed episodes of venous thromboembolism and the relationship between incidence and exposure to high-risk situations.
Results: Nine venous thromboembolic events were observed in 1564 observation-years, resulting in an annual incidence of 0.58% (95% CI, 0.26% to 1.10%). The incidence of spontaneous venous thromboembolism was 0.26% (CI, 0.07% to 0.65%) per year; 3.5% (CI, 0.1% to 17.8%) per episode of surgery, trauma, or immobilization; 0.0% (CI, 0.0% to 19.5%) per pregnancy; 1.8% (CI, 0.4% to 5.2%) per year of oral contraceptive use; and 2.9% (CI, 0.8% to 15.3%) per year of use of hormone replacement therapy.
Conclusions: The absolute annual incidence of spontaneous venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation is low and does not justify routine screening of the families of symptomatic patients.
Article and Author Information
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Grant Support: By the Zorg Onderzoek Nederland (grant 28-2783).
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Requests for Single Reprints: Saskia Middeldorp, MD, Department of Vascular Medicine, Academic Medical Center F4-277, Box 22700, 1100 DE Amsterdam, the Netherlands.
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Current Author Addresses: Drs. Middeldorp, Koopman, and Büller: Department of Vascular Medicine, Academic Medical Center F4-277, Box 22700, 1100 DE Amsterdam, the Netherlands.
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Drs. Meinardi and van der Meer: Department of Hematology, Division of Hemostasis, Thrombosis and Rheology, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.
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Drs. van Pampus and Hamulyák: Department of Hematology, Academic Hospital Maastricht, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands.
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Dr. Prins: Department of Clinical Epidemiology and Medical Technology Assessment, Academic Hospital Maastricht, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands.
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Author Contributions: Conception and design: S. Middeldorp, M.M.W. Koopman, K. Hamulyák, J. van der Meer, M.H. Prins, H.R. Büller.
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Analysis and interpretation of the data: S. Middeldorp, M.H. Prins, H.R. Büller.
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Drafting of the article: S. Middeldorp, H.R. Büller.
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Critical revision of the article for important intellectual content: J.R. Meinardi, M.M.W. Koopman, E.C.M. van Pampus, K. Hamulyák, J. van der Meer.
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Final approval of the article: S. Middeldorp, J.R. Meinardi, M.M.W. Koopman, E.C.M. van Pampus, K. Hamulyák, J. van der Meer, M.H. Prins, H.R. Büller.
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Provision of study materials or patients: S. Middeldorp, J.R. Meinardi, M.M.W. Koopman, E.C.M. van Pampus, K. Hamulyák, J. van der Meer.
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Statistical expertise: S. Middeldorp, M.H. Prins.
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Obtaining of funding: S. Middeldorp, H.R. Büller.
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Administrative, technical, or logistic support: S. Middeldorp, E.C.M. van Pampus, K. Hamulyák, J. van der Meer, M.H. Prins.
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Collection and assembly of data: S. Middeldorp, J.R. Meinardi, E.C.M. van Pampus, K. Hamulyák, J. van der Meer.
- Copyright ©2004 by the American College of Physicians
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