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Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: a systematic review Segal JB; Brotman DJ; Necochea AJ; Emadi A; Samal L; Wilson LM; Crim MT; Bass EBJAMA 2009[Jun]; 301 (23): 2472-85CONTEXT: Testing for genetic risks for venous thromboembolism (VTE) is common, but the safety and utility of such testing need review. OBJECTIVES: To define rates of recurrent VTE among adults with VTE with a factor V Leiden (FVL) or prothrombin G20210A mutation compared with those without such mutations; to define rates of VTE among family members of adults with a FVL or prothrombin G20210A mutation according to presence or absence of a mutation; and to assess whether testing adults with VTE for FVL or prothrombin G20210A improves outcomes. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, and PsycInfo through December 2008. STUDY SELECTION: Studies were included if they assessed rates of VTE in individuals with a history of VTE who were tested for FVL or prothrombin G20210A or in family members of individuals with these mutations. Studies assessing the harms and benefits associated with testing were also included. DATA EXTRACTION: Two investigators abstracted data and assessed study quality. We pooled the odds of VTE associated with the mutations using random-effects models. We assessed the strength of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: We reviewed 7777 titles and included 46 articles. Heterozygosity (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.14-2.12) and homozygosity (OR, 2.65; 95% CI, 1.2-6.0) for FVL in probands are predictive of recurrent VTE compared with individuals without FVL. Heterozygosity for FVL predicts VTE in family members (OR, 3.5; 95% CI, 2.5-5.0), as does homozygosity for FVL (OR, 18; 95% CI, 7.8-40) compared with family members of adults without FVL. Heterozygosity for prothrombin G20210A is not predictive of recurrent VTE in probands compared with individuals without prothrombin G20210A (OR, 1.45; 95% CI, 0.96-2.2). Evidence is insufficient regarding the predictive value of prothrombin G20210A homozygosity for recurrent VTE and the risk of VTE in family members of individuals with prothrombin G20210A. High-grade evidence supports that anticoagulation reduces recurrent VTE events in probands with either mutation. Low-grade evidence supports that this risk reduction is similar to that in individuals with a history of VTE and without mutations. CONCLUSIONS: Patients with FVL are at increased risk of recurrent VTE compared with patients with VTE without this mutation. However, it is unknown whether testing for FVL or prothrombin G20210A improves outcomes in adults with VTE or in family members of those with a mutation.|*Mutation[MESH]|Adult[MESH]|Factor V/*genetics[MESH]|Genetic Testing[MESH]|Humans[MESH]|Predictive Value of Tests[MESH]|Prothrombin/*genetics[MESH]|Risk Factors[MESH]|Venous Thromboembolism/*blood/epidemiology/*genetics[MESH] |
