BACKGROUND: Venous thromboembolism (VTE) is thought to result from interactions between multiple genetic and environmental risk factors. OBJECTIVE: To assess the contribution of multiple thrombophilic defects and exogenous risk factors to the absolute risk for VTE. DESIGN: Retrospective family cohort study. SETTING: Single university hospital. PARTICIPANTS: 468 relatives of 91 probands with a symptomatic hereditary deficiency of protein S, protein C, or antithrombin. MEASUREMENTS: 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. RESULTS: 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]). LIMITATIONS: This was a retrospective study without the ability to distinguish interactions between specific thrombophilic deficiencies and defects. CONCLUSION: 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.
BACKGROUND:Venous thromboembolism (VTE) is thought to result from interactions between multiple genetic and environmental risk factors. OBJECTIVE: To assess the contribution of multiple thrombophilic defects and exogenous risk factors to the absolute risk for VTE. DESIGN: Retrospective family cohort study. SETTING: Single university hospital. PARTICIPANTS: 468 relatives of 91 probands with a symptomatic hereditary deficiency of protein S, protein C, or antithrombin. MEASUREMENTS: 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. RESULTS: 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]). LIMITATIONS: This was a retrospective study without the ability to distinguish interactions between specific thrombophilic deficiencies and defects. CONCLUSION: 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.
Authors: Benedetto Simone; Valerio De Stefano; Emanuele Leoncini; Jeppe Zacho; Ida Martinelli; Joseph Emmerich; Elena Rossi; Aaron R Folsom; Wassim Y Almawi; Pierre Y Scarabin; Martin den Heijer; Mary Cushman; Silvana Penco; Amparo Vaya; Pantep Angchaisuksiri; Gulfer Okumus; Donato Gemmati; Simona Cima; Nejat Akar; Kivilcim I Oguzulgen; Véronique Ducros; Christoph Lichy; Consuelo Fernandez-Miranda; Andrzej Szczeklik; José A Nieto; Jose Domingo Torres; Véronique Le Cam-Duchez; Petar Ivanov; Carlos Cantu-Brito; Veronika M Shmeleva; Mojka Stegnar; Dotun Ogunyemi; Suhair S Eid; Nicola Nicolotti; Emma De Feo; Walter Ricciardi; Stefania Boccia Journal: Eur J Epidemiol Date: 2013-07-31 Impact factor: 8.082
Authors: Anja B U Mäkelburg; Nic J G M Veeger; Saskia Middeldorp; Karly Hamulyák; Martin H Prins; Harry R Büller; Willem M Lijfering Journal: Haematologica Date: 2009-12-08 Impact factor: 9.941
Authors: James D F Calder; Richard Freeman; Erica Domeij-Arverud; C Niek van Dijk; Paul W Ackermann Journal: Knee Surg Sports Traumatol Arthrosc Date: 2016-03-18 Impact factor: 4.342
Authors: Joakim K Sejrup; Vania M Morelli; Maja-Lisa Løchen; Inger Njølstad; Ellisiv B Mathiesen; Tom Wilsgaard; John-Bjarne Hansen; Sigrid K Brækkan Journal: Res Pract Thromb Haemost Date: 2020-01-27