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Risk for Venous Thromboembolism in Carriers of the Factor V Leiden Mutation
- Saskia Middeldorp, MD;
- Harry R. Büller, MD; and
- Martin H. Prins, MD
- Academic Medical Center; 1100 DE Amsterdam, the Netherlands (Middeldorp, Büller) Academic Hospital Maastricht; 6229 HX Maastricht, the Netherlands (Prins)
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IN RESPONSE:
For our prospective cohort study of asymptomatic carriers, we by definition excluded relatives with previous venous thromboembolism. However, the symptomatic carriers of the factor V Leiden mutation actually were represented as the group that had had an outcome event in our earlier retrospective family study (1), in which all relatives were included. We observed virtually the same absolute yearly incidence in our earlier study as in our prospective study (0.45% [95% CI, 0.28% to 0.61%] vs. 0.58% [CI, 0.26% to 1.10%]). Since these incidences are much lower than the known major bleeding risks associated with the prophylactic use of vitamin K antagonists (2), prophylaxis would do more harm than good. Furthermore, screening to initiate intensified prophylaxis in carriers during high-risk situations alone would, at best, prevent half of all episodes, although it is as yet unknown whether this action is safe and effective. In our article, we extensively discussed the dilemmas surrounding the optimal strategy for prophylaxis during the postpartum period and the attitude toward estrogen use, which is indeed more complicated.
Dr. Orwoll suggests that patients with the factor V Leiden mutation should be counseled and told that their relatives with the mutation are at what she considers a “clearly high risk” for venous thromboembolism. To put this into perspective, we used known age-specific incidences of venous thrombosis in the general population to calculate that the lifetime risk for venous thrombosis for any individual is approximately 15% (Figure) (3).
We acknowledge that the factor V Leiden mutation increases the risk for venous thromboembolism and that carriers usually have these events at a younger age than noncarriers, although precise lifetime risk estimates are not available. Our study was set up to estimate the absolute annual incidence and to balance it against the known risks associated with anticoagulant prophylaxis. Given the observed incidence of spontaneous venous thromboembolism, and the limits of the 95% CI (0.26% and 0.65% per year), our study provided an estimate precise enough to guide this decision, which obviates the need for longer follow-up. We remain convinced that the absolute risk for spontaneous venous thromboembolism in carriers of the factor V Leiden mutation, even though higher than that in the general population, is too low to justify family screening and that future research should address potential subgroups in whom screening might be beneficial.
Saskia Middeldorp, MD
Harry R. Büller, MD
Academic Medical Center; 1100 DE Amsterdam, the Netherlands
Martin H. Prins, MD
Academic Hospital Maastricht; 6229 HX Maastricht, the Netherlands
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
