Routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members

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.

EGAPP Recommendation Statement: The 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 overall certainty of these findings was deemed “moderate.” 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. Based on the available evidence, the certainty of net health benefit was deemed “low.” 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.

EGAPP Recommendation (January 2011)

Evidence Report (June 2009)

Supplementary Manuscript (June 2009)

CDC Summary of EGAPP Recommendation (January 2011)

Key Questions:

  • Question 1: Does FVL testing, alone or in combination with prothrombin G20210A testing, lead to improved clinical outcomes (e.g., avoidance of a recurrent VTE) in adults with a personal history of VTE or to improved clinical outcomes (e.g., avoidance of an initial VTE) in adult family members of mutation-positive individuals? Are testing results useful in medical, personal, or public health decision making?

  • Question 2: What is the evidence regarding the analytic validity of existing diagnostic tests for the FVL mutation and the prothrombin G20210A mutation, specifically their analytic sensitivity and specificity, reproducibility, and robustness (sources of variability)?

  • Question 3a: What is the evidence that the presence of FVL alone, prothrombin G20210A alone, or the two in combination predicts the risk of recurrent VTE in individuals (probands) who have had VTE and predicts the risk of VTE in the probands’ family members who have been tested? Does the testing add predictive information beyond clinical data?

  • Question 3b: What is the evidence that demographic or clinical factors modify the relationship between the presence of FVL or prothrombin G20210A and the risk of VTE?

  • Question 4a: What is the evidence that clinicians manage patients differently based on the results of testing for FVL or prothrombin G20210A? How do clinicians manage anticoagulation of individuals who have had testing, as compared to those who have not had testing? What other diagnostic tests do clinicians order or not order, based on testing results? What recommendations do clinicians make regarding other therapies and exposures, based on testing results?

  • Question 4b: What is the evidence that testing, and the resultant management, reduces VTE related outcomes or has other benefits in individuals who have had VTE or in the probands’ family members who have been tested?

  • Question 4c: What is the evidence of harms to individuals with VTE or to the probands’ family members who are tested for FVL or prothrombin G20210A as a result of testing or as a result of changed management based on the test results?

  • Question 4d: What is the evidence that testing for FVL alone, prothrombin G20210A alone, or the two tests in combination is a cost-effective strategy when caring for a patient with VTE or a family member of a proband?

Why EGAPP Selected this Topic for Review:

Key Criteria: Widely used drug to treat thrombophilia, possible inadequate data

Other Considerations: Reviews by others, but dependant on clinical scenario