April 10, 2006Archives of Internal Medicine298 citations
View Full PaperRisk of Recurrent Venous Thromboembolism in Patients With Common Thrombophilia
Key Result
Heterozygous factor V Leiden and prothrombin G20210A polymorphisms were associated with modestly increased odds of recurrent VTE (OR 1.41 and OR 1.72, respectively) after a first event.
Study Design
Type
Meta-Analysis (n=3,104)
Structured PICO
Does the presence of heterozygous factor V Leiden or prothrombin G20210A polymorphism increase the risk of recurrent VTE in patients with a first episode of VTE?
P
Population
13 cohort studies pooling patients with a first episode of venous thromboembolism (VTE) following discontinuation of anticoagulation. FVL analysis included 10 studies (n=3104) and prothrombin G20210A analysis included 9 studies (n=2903).
I
Intervention
Presence of heterozygous factor V Leiden (FVL) or prothrombin G20210A polymorphism
C
Comparator
Absence of heterozygous factor V Leiden (FVL) or prothrombin G20210A polymorphism
O
Outcome
Incidence of objectively confirmed recurrent VTE following discontinuation of anticoagulationhard clinical
Heterozygous FVL and prothrombin G20210A modestly increase the risk of recurrent VTE, but the magnitude does not justify extended-duration anticoagulation or routine testing.
Main Result
Effect estimate: OR 1.41 (FVL), OR 1.72 (prothrombin G20210A) (95% CI 1.14-1.75 (FVL), 1.27-2.31 (prothrombin G20210A))
Abstract
The 2 most common genetic polymorphisms that predispose to a first episode of venous thromboembolism (VTE) are factor V Leiden (FVL) and prothrombin G20210A. However, the effect of these polymorphisms on the risk of recurrent VTE is unclear. We performed a meta-analysis to obtain best estimates of the relative risk of recurrent VTE associated with these genetic polymorphisms. Electronic and manual searches were used to identify cohort studies of patients with a first episode of VTE that reported the incidence of objectively confirmed recurrence following discontinuation of anticoagulation among those with or without heterozygous FVL or prothrombin G20210A polymorphism. Thirteen reports fulfilled our criteria for inclusion. Pooled results from 10 studies involving 3104 patients with first-ever VTE revealed that FVL was present in 21.4% of patients (95% confidence interval CI, 20%-23%) and associated with an increased odds of recurrent VTE of 1.41 (95% CI, 1.14-1.75; P = .08 for heterogeneity). Pooled results from 9 studies involving 2903 patients with first-ever VTE revealed that prothrombin G20210A was present in 9.7% of patients (95% CI, 9%-11%) and associated with an increased odds of recurrent VTE of 1.72 (95% CI, 1.27-2.31; P = .19). The estimated population-attributable risk of recurrence for FVL was 9.0% (95% CI, 4.5%-13.2%) and for prothrombin G20210A was 6.7% (95% CI, 3.4%-9.9%). Heterozygous FVL and prothrombin G20210A are each associated with a significantly increased risk of recurrent VTE after a first event, but the magnitude of the increase in risk is modest and by itself is unlikely to merit extended-duration anticoagulation. These data call into question the cost-effectiveness of routine testing for these common inherited thrombophilic polymorphisms among patients with a first episode of VTE.