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To review the use of Factor V Leiden (FVL) R506Q and/or prothrombin 20210G>A mutation testing in adults with a personal history of venous thromboembolism (VTE), and in asymptomatic adult family members of people with these mutations.

The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group conducted a systematic evidence-based review of whether FVL and/or prothrombin mutation testing leads to improved clinical outcomes and if the test results are useful in medical, personal, or public health decision making. The framework reviewed evidence in relation to the analytical and clinical validity and the clinical utility of the mutation testing, as well as other factors related to implementation of the test.

Evidence supported high analytic validity (accurate mutation testing) but gave mixed results for clinical. People carrying the FVL mutation and family members were found to be at increased risk of recurrent VTE and initial episodes of VTE, respectively, but the evidence for prothrombin mutations was weaker. The evidence regarding clinical utility indicates that longer-term anticoagulation treatment reduces the recurrence of VTE regardless of mutation status. There is no evidence that knowledge of FVL and/or prothrombin mutation status in cases or family members affects treatment to avoid recurrence or initial VTE episodes and that benefits were unlikely to outweigh harms in family members. Modeled cost-effectiveness studies also suggest that routine mutation testing is not cost-effective although the evidence needs updating.

There is adequate (moderate) evidence to recommend against routine testing for FVL and/or prothrombin mutations in adults with idiopathic VTE or in asymptomatic family members of a mutation carrying case. There is insufficient evidence to determine whether mutation testing may have clinical utility in certain cases. These recommendations do not extend to patients with other risk factors, such as oral contraceptive use.

This evidence-based guideline statement agrees with an earlier report that showed no clear clinical benefit arising from FVL or prothrombin mutation testing in idiopathic VTE cases (see previous news). With millions of FVL tests performed worldwide annually, this recommendation statement should be of help for health professionals considering thrombophilia testing, although the working group did highlight that in the US, uptake of testing did not follow existing recommendations. An accompanying editorial suggested that the best advice may be “if you don’t know what to do with the test result, don’t test”.