Predictive Value of Factor V Leiden and Prothrombin G20210A in Adults With Venous Thromboembolism and in Family Members of Those With a Mutation

Abstract

LINICIANS TEST FOR PROTHROMbotic genetic mutations including factor V Leiden (FVL) (612309.001) and prothrombin G20210A (176930.0009) when treating patients who have had or are at risk of venous thromboembolism (VTE). Factor V Leiden refers to a single base change in the factor V gene (G1691A) that eliminates 1 of its 3 activated protein C cleavage sites. Consequently, factor V is inactivated at a lower rate, leading to more thrombin generation. 1 A single FVL allele is present in about 5%, 2.2%, and 1.2% of white, Hispanic and African American populations in the United States. 2 The prothrombin (factor II) mutation is the second most common inherited risk factor for VTE. This allele is present in 1.1% of non-Hispanic whites and Mexican Americans and in 0.3% of African Americans. 3 The G20210A mutation is associated with an increase in prothrombin levels by approximately 30% in heterozygotes and by 70% in ho-CME available online at www.jamaarchivescme.com and questions on p 2509. Context 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 SourcesWe 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 ExtractionTwo 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. ResultsWe 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 memb...

Lack of association between the prothrombin rs1799963 polymorphism and juvenile myoclonic epilepsy

“…The mutant allele rs1799963*A was not detected in Afro-descendants individuals. These findings are in agreement with other reports showing that the prothrombin polymorphism varies among different ethnic groups, presenting a very low frequency in Afro-descendants (0.3%) 22 .…”

“…The mutant allele rs1799963*A was not detected in Afro-descendants individuals. These findings are in agreement with other reports showing that the prothrombin polymorphism varies among different ethnic groups, presenting a very low frequency in Afro-descendants (0.3%) 22 .The frequencies of genotypes (98% for rs1799963*GG and 2% for rs1799963*GA) and alleles (99% for rs1799963*G and 1% for rs1799963*A) in northeastern Brazilian population (patients and control) observed in this study are consistent with results in other Brazilian subpopulations reported in previous studies. In fact, in general Brazilian population the mutant allele frequency ranged between 0.7%-3.6% (rs1799963*A) 23,24,25 .…”

Cancer‐associated thrombosis: The search for the holy grail continues

“…Therefore, initial studies investigating CAT have focused on these “classical” targets. Factor V Leiden—a genetic variant that is resistant to inactivation by activated protein C—confers an increased risk of VTE with an odds ratio of 3.49 in the healthy population 31. While some studies suggest a two‐ to five‐fold increased risk of VTE in cancer patients with Factor V Leiden,32, 33, 34 other cohort studies were unable to confirm this association 35, 36, 37.…”

Duration of Anticoagulation: Applying the Guidelines and Beyond

“…A pooled analysis of the literature found the risk associated with factor V Leiden mutation to be significantly increased, but the magnitude was so modest that this by itself does not merit committing a patient to long-term anticoagulation (odds ratios of approximately 1.5 each for factor V Leiden and prothrombin G20210A). 15,16 Hereditary deficiencies of antithrombin, protein C, or protein S are much less frequently encountered in clinical practice, and one of these disorders will be identified in fewer than 5% of patients presenting with a first unprovoked episode of VTE; this is increased up to about 15% if the patient is under age 50 and has a positive family history. Patients with these less common thrombophilic defects may merit long-term anticoagulation, particularly if other first-degree family members have sustained VTE.…”