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; Harry R. Büller, MD
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.
Middeldorp S, Meinardi JR, Koopman MM, van Pampus EC, Hamulyák K, van der Meer J, et al. A Prospective Study of Asymptomatic Carriers of the Factor V Leiden Mutation To Determine the Incidence of Venous Thromboembolism. Ann Intern Med. 2001;135:322-327. doi: 10.7326/0003-4819-135-5-200109040-00008
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Published: Ann Intern Med. 2001;135(5):322-327.
Until 1994, only isolated deficiencies of the physiologic inhibitors of the coagulation system, antithrombin, protein C, and protein S, were recognized as inherited risk factors for venous thromboembolism. These deficiencies could be detected only in a small minority of patients with the disease (1). In 1994, resistance to activated protein C was reported as a new and prevalent risk factor for venous thrombosis (2). Soon thereafter, this resistance was found to be caused by a single point mutation (also called factor V Leiden mutation or FV:Q506 mutation) in the factor V gene at the major cleavage site of activated protein C (3-5). The factor V Leiden mutation can be found in 20% to 50% of patients with documented venous thrombosis (2, 6) and has an overall prevalence of approximately 5% in western populations (7). Case–control studies have shown a three-fold to sevenfold increased risk for venous thromboembolism in heterozygous carriers of the factor V Leiden mutation compared with healthy controls (2, 6, 8, 9).
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