Risk of venous thromboembolism in carriers of factor V Leiden with a concomitant inherited thrombophilic defect: a retrospective analysis
| Autor: | H. R. Büller, Saskia Middeldorp, Johan R. Meinardi, J van der Meer, E. C. M. Van Pampus, Martin H. Prins, Karly Hamulyák, Mmw Koopman, PJ de Kam |
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| Přispěvatelé: | Other departments, Faculteit Medische Wetenschappen/UMCG |
| Rok vydání: | 2001 |
| Předmět: |
GLN MUTATION
Male Gastroenterology Protein S 3'-UNTRANSLATED REGION Pregnancy Risk Factors hemic and lymphatic diseases Prevalence Thrombophilia Medicine DEEP-VEIN THROMBOSIS Venous Thrombosis biology Hazard ratio Factor V Hematology General Medicine Middle Aged DEFICIENCY ALLELE activated protein C resistance Regression Analysis Female medicine.drug Adult Heterozygote medicine.medical_specialty PROTHROMBIN GENE ACTIVATED PROTEIN-C Thromboembolism Internal medicine Factor V Leiden Coagulopathy Humans cardiovascular diseases Risk factor Retrospective Studies Family Health business.industry medicine.disease Surgery biology.protein blood coagulation disorders Activated protein C resistance business RESISTANCE Protein C FAMILY MEMBERS |
| Zdroj: | Blood coagulation & fibrinolysis, 12(8), 713-720. Lippincott Williams and Wilkins Blood Coagulation & Fibrinolysis, 12(8), 713-720 |
| ISSN: | 0957-5235 |
| DOI: | 10.1097/00001721-200112000-00014 |
| Popis: | Factor V Leiden is the most common genetic defect associated with venous thromboembolism. Its clinical expression is limited and shows a wide intrafamilial and interfamilial variation, which might be explained by the influence of other genetic risk factors. We retrospectively studied 226 patients with factor V Leiden and documented venous thromboembolism (probands) and 400 first-degree carrier relatives to assess the contribution of concomitant genetic risk factors to the occurrence of venous thromboembolism. The prothrombin G20210A mutation was found in 8.3%, homozygosity of factor V Leiden in 7.2%, and inherited deficiencies of antithrombin, protein C or protein S in 4.7% of symptomatic carriers (probands and relatives), as compared with 6.0, 3.4 and 0.9% of asymptomatic carriers, respectively. The total follow-up time in relatives was 11049 years. Prevalences of venous thromboembolism were 10.8% in single heterozygous factor V Leiden carrier relatives, 16.0% in double-heterozygotes for factor V Leiden and the prothrombin mutation, 36.8% in homozygotes for factor V Leiden, and 40.0% in double-heterozygotes for factor V Leiden and an inherited deficiency of protein C or protein S. Annual incidences in these groups were 0.39, 0.57, 1.41, and 4.76%, respectively. Multivariate analysis showed a small, non-significant additional effect of the prothrombin mutation on the risk of venous thromboembolism in heterozygotes for factor V Leiden [adjusted hazard ratio, 1.3; 95% confidence interval (CI), 0.5-3.8]. This effect was more pronounced for homozygosity of factor V Leiden (adjusted hazard ratio, 3.9; 95% CI, 1.7-9.0) and inherited protein C or protein S deficiencies (adjusted hazard ratio, 17.5; 95% CI, 3.8-81.2). Our data provide evidence of clustering of the evaluated genetic thrombophilic defects in symptomatic factor V Leiden carriers and support the assumption that the clinical expression of factor V Leiden depends on clustering in a part of carriers. Blood Coagul Fibrinolysis 12:713-720 (C) 2001 Lippincott Williams & Wilkins. |
| Databáze: | OpenAIRE |
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