Impact of environmental and hereditary risk factors on the clinical manifestation of thrombophilia in homozygous carriers of factor V:G1691A |
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| Authors: | S. Ehrenforth,L. Nemes,C. Mannhalter,F. R. Rosendaal,S. Koder,C. Zoghlami-Rintelen,I. Scharrer, I. Pabinger§ |
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| Affiliation: | Department of Internal Medicine I, University Hospital Frankfurt, Germany;;National Hemophilia Center, National Institute of Hematology and Immunology, Budapest, Hungary;;Department of Laboratory Medicine, Divison of Molecular Biology, University Hospital Vienna, Vienna, Austria;;Department of Clinical Epidemiology, Hemostasis and Research Center, Leiden University Medical Center, Leiden the Netherlands;and;Department of Internal Medicine I, University Hospital Vienna, Vienna, Austria |
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| Abstract: | Summary. Background : Limited data exist on the clinical manifestations of homozygous factor (F)V:G1691A mutation (FV Leiden) and the impact of environmental and genetic risk factors. Objectives : To assess the contribution of these factors on the thrombophilic phenotype. Patients and methods : In a retrospective multicenter cohort study 165 individuals with homozygous FV:G1691A mutation, of whom 129 had previous venous thromboembolism (VTE), were included. To study the role of environmental risk factors, patients were compared by the use of a standardized questionnaire to 165 sex- and age-matched individuals (reference group A); of these, two had previous VTE. To assess the role of genetic risk factors, factor (F)II:G20210A and MTHFR:C677T were determined in individuals homozygous for FV:G1691A and in 177 healthy individuals without previous VTE (reference group B). Results : The first VTE occurred significantly earlier in women (median age 25 years) than men (35.5 years). In 81% of women and 29% of men an environmental risk factor was present before first VTE. Oral contraceptives increased the risk of thrombosis 4-fold [odds ratio (OR) 4.0, 95% confidence interval (CI) 1.7, 10.4] in women with homozygous FV:G1691A. Postoperative and post-traumatic VTE as first manifestation occurred in 13% and 15% of surgical/traumatic events in patients and in 0.7% and 1.8% in reference group A, respectively (OR 19.7, 95% CI 2.5, 154 and OR 9.2, 95% CI 1.1, 79.4). Heterozygous FII:G20210A was more prevalent in symptomatic patients (11.7%) compared with reference group B (2.8%, OR 4.6, 95% CI 1.6, 13.2). The prevalence of homozygous MTHFR:C677T genotype was similar in patients and reference group B. Conclusions : Our study supports the concept of thrombophilia as a multifactorial disorder. The knowledge of coexisting factors predisposing to VTE is useful for medical advice for primary and secondary prophylaxis in these patients. |
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| Keywords: | factor V Leiden homozygous factor V:G1691A oral contraceptives prothrombin G20210A variation thrombophilia venous thrombosis |
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