Jan-Leendert P. Brouwer, MD; Nic J.G.M. Veeger, MSc; Hanneke C. Kluin-Nelemans, MD, PhD; Jan van der Meer, MD, PhD
Grant Support: None.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Jan van der Meer, MD, PhD, Department of Hematology, Division of Haemostasis, Thrombosis and Rheology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands; e-mail, email@example.com.
Current Author Addresses: Drs. Brouwer, Kluin-Nelemans, and van der Meer: Department of Hematology, Division of Haemostasis, Thrombosis and Rheology, University Medical Center Groningen, Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.
Mr. Veeger: Department of Epidemiology, Trial Coordination Center, University Medical Center Groningen, Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.
Author Contributions: Conception and design: J. van der Meer.
Analysis and interpretation of the data: J.-L.P. Brouwer, N.J.G.M. Veeger, H.C. Kluin-Nelemans, J. van der Meer.
Drafting of the article: J.-L.P. Brouwer.
Critical revision of the article for important intellectual content: N.J.G.M. Veeger, H.C. Kluin-Nelemans, J. van der Meer.
Final approval of the article: J.-L.P. Brouwer, N.J.G.M. Veeger, H.C. Kluin-Nelemans, J. van der Meer.
Provision of study materials or patients: J.-L.P. Brouwer, J. van der Meer.
Statistical expertise: N.J.G.M. Veeger.
Obtaining of funding: J. van der Meer.
Administrative, technical, or logistic support: J.-L.P. Brouwer.
Collection and assembly of data: J.-L.P. Brouwer, J. van der Meer.
Venous thromboembolism (VTE) is thought to result from interactions between multiple genetic and environmental risk factors.
To assess the contribution of multiple thrombophilic defects and exogenous risk factors to the absolute risk for VTE.
Retrospective family cohort study.
Single university hospital.
468 relatives of 91 probands with a symptomatic hereditary deficiency of protein S, protein C, or antithrombin.
All relatives were tested for 10 thrombophilic deficiencies and defects in addition to the index deficiency and were assessed for exogenous risk factors (surgery, trauma, immobilization, use of oral contraceptives, and pregnancy). The authors compared annual incidences and relative risks for VTE in deficient and nondeficient relatives.
Annual incidences of VTE in relatives with 0, 1, and 2 or more additional thrombophilic deficiencies or defects were 1.16 (95% CI, 0.60 to 2.03), 1.75 (CI, 1.17 to 2.53), and 2.64 (CI, 1.67 to 3.96) per 100 person-years, respectively, compared with 0.06 (CI, 0.002 to 0.33) per 100 person-years in nondeficient relatives without additional deficiencies or defects. Adjusted relative risks were 16.3 (CI, 2.0 to 131.0), 50.3 (6.5 to 389.7), and 102.8 (12.5 to 843.4). Of deficient relatives, 38% with no additional defect, 57% with 1 additional defect, and 81% with 2 or more additional defects had VTE at age 65 years compared with 5% of nondeficient relatives (P < 0.001). In deficient relatives with additional deficiencies or defects, exogenous risk factors increased the risk for VTE from 1.20% to 2.51% per year (relative risk, 2.1 [CI, 1.1 to 4.2]).
This was a retrospective study without the ability to distinguish interactions between specific thrombophilic deficiencies and defects.
Additional thrombophilic defects and exogenous risk factors increase the risk for VTE in persons with hereditary deficiencies of protein S, protein C, or antithrombin and provide evidence that multiple genetic and environmental risk factors contribute to VTE.
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Brouwer JP, Veeger NJ, Kluin-Nelemans HC, van der Meer J. The Pathogenesis of Venous Thromboembolism: Evidence for Multiple Interrelated Causes. Ann Intern Med. 2006;145:807-815. doi: 10.7326/0003-4819-145-11-200612050-00005
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Published: Ann Intern Med. 2006;145(11):807-815.
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