A Prospective Study of Asymptomatic Carriers of the Factor V Leiden Mutation To Determine the Incidence of Venous Thromboembolism

  1. Saskia Middeldorp, MD;
  2. Johan R. Meinardi, MD;
  3. Maria M.W. Koopman, MD;
  4. Elisabeth C.M. van Pampus, MD;
  5. Karly Hamulyák, MD;
  6. Jan van der Meer, MD;
  7. Martin H. Prins, MD; and
  8. Harry R. Büller, MD
  1. 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

    • Grant Support: By the Zorg Onderzoek Nederland (grant 28-2783).

    • Requests for Single Reprints: Saskia Middeldorp, MD, Department of Vascular Medicine, Academic Medical Center F4-277, Box 22700, 1100 DE Amsterdam, the Netherlands.

    • Current Author Addresses: Drs. Middeldorp, Koopman, and Büller: Department of Vascular Medicine, Academic Medical Center F4-277, Box 22700, 1100 DE Amsterdam, the Netherlands.

    • 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.

    • Drs. van Pampus and Hamulyák: Department of Hematology, Academic Hospital Maastricht, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands.

    • Dr. Prins: Department of Clinical Epidemiology and Medical Technology Assessment, Academic Hospital Maastricht, P. Debyelaan 25, 6229 HX Maastricht, the Netherlands.

    • Author Contributions: Conception and design: S. Middeldorp, M.M.W. Koopman, K. Hamulyák, J. van der Meer, M.H. Prins, H.R. Büller.

    • Analysis and interpretation of the data: S. Middeldorp, M.H. Prins, H.R. Büller.

    • Drafting of the article: S. Middeldorp, H.R. Büller.

    • 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.

    • 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.

    • 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.

    • Statistical expertise: S. Middeldorp, M.H. Prins.

    • Obtaining of funding: S. Middeldorp, H.R. Büller.

    • Administrative, technical, or logistic support: S. Middeldorp, E.C.M. van Pampus, K. Hamulyák, J. van der Meer, M.H. Prins.

    • Collection and assembly of data: S. Middeldorp, J.R. Meinardi, E.C.M. van Pampus, K. Hamulyák, J. van der Meer.

    Summary for Patients

    • Summaries for Patients:Blood Clots in People with the Factor V Leiden Mutation Ann Intern Med September 4, 2001 135:S34
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    1. Ann Intern Med September 4, 2001 vol. 135 no. 5 322-327
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