Genetic Tests for Idiopathic Venous Thromboembolism: EGAPP™ Recommendation


Factor V Leiden (FVL) and prothrombin (PT) genetic variants are associated with an increased risk of future venous thrombosis or pulmonary embolism (also known as blood clots in the deep veins or lungs). Idiopathic venous thromboembolism (VTE) includes deep vein thrombosis or pulmonary embolism, and in the context of the EGAPP recommendation, refers to thrombotic events in which no underlying cause is apparent.

Genetic tests for FVL and PT variants are widely available and commonly used. One current use of these tests is to inform decisions on anticoagulant medication in order to decrease the risk of future clots.

The EGAPP™ Working Group evaluated available scientific evidence to see whether FVL and PT genetic testing is valid and useful for:

  • adults with thrombotic events in which no underlying cause is apparent, and
  • their adult family members with no history or symptoms of thrombotic events, for medical decision making on preventive use of anticoagulants.

EGAPP™ Recommendation Statement

Summary of Findings on Factor V Leiden and Prothrombin

In 2011, the independent Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) Working Group found enough evidence to recommend against routine testing for FVL and PT gene variants in the following specific scenarios:

  • adults who have idiopathic VTE, since longer term preventive treatment with anticoagulant medication offers similar benefits to patients whether or not they have these genetic variations; and
  • their adult family members who do not have a history or symptoms of VTE, when the testing is conducted to help decide whether to treat them preventively with anticoagulant medication. The EGAPP Working Group stated that, in the absence of other risk factors, for most of these family members, the benefit of possibly avoiding a first VTE event through anticoagulant medication was offset by the risk of hemorrhage from this medication. However, the EGAPP Working Group encouraged further research to determine whether genetic testing might yield a net health benefit in special circumstances.

The evidence reviewed for this recommendation focused primarily on idiopathic VTE. Therefore, the recommendation does not extend to patients with VTE that is associated with commonly-recognized modifiable risk factors, such as contraceptive use or estrogen replacement. Also, the recommendation does not address other reasons for genetic testing of relatives except for informing preventive treatment with anticoagulant medication.

The new recommendation is based on a systematic evidence review conducted by the Johns Hopkins Evidence-based Practice Center and funded by the Centers for Disease Control and Prevention (CDC). The corresponding evidence report was published by the Agency for Healthcare Research and Quality (AHRQ) in June 2009. The EGAPP recommendation is published in the January 2011 issue of Genetics in Medicine. Links to these and other CDC-funded evidence reports used by the EGAPP Working Group are available on the EGAPP Working Group Web site.

EGAPP™ Recommendation Statement

“The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group found adequate evidence to recommend against routine testing for Factor V Leiden (FVL) and/or prothrombin 20210G>A (PT) in the following circumstances: (1) adults with idiopathic venous thromboembolism (VTE). In such cases, longer term secondary prophylaxis to avoid recurrence offers similar benefits to patients with and without one or more of these mutations. (2) Asymptomatic adult family members of patients with VTE and an FVL or PT mutation, for the purpose of considering primary prophylactic anticoagulation. Potential benefits are unlikely to exceed potential harms. The evidence was insufficient to determine whether FVL/PT testing might have clinical utility in some circumstances, such as for identifying FVL homozygosity among asymptomatic family members of adults with idiopathic VTE or counseling patients about the risks and benefits of antithrombotic therapy. The recommendations do not extend to patients with other risk factors for thrombosis, such as contraceptive use, as the evidence review that serves as the basis for the recommendations focused primarily on idiopathic VTE.”




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