Genetic testing for thrombosis: still no evidence of clinical benefit

12 July 2009

A recent publication reports on a study to assess the value of genetic testing for the mutations most commonly associated with increased susceptibility to thrombosis in prevention. The JAMA paper summarises the findings of research by the US Agency for Healthcare Research and Quality (AHRQ) on behalf of the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative. Venous thromboembolism (VTE) is a term for clots in the blood vessels, typically deep-vein thrombosis (DVT) and the life threatening complication pulmonary embolism. Factor V Leiden (FVL) and prothrombin G20210A are the most common mutations known to be associated with increased susceptibility to DVT, and genetic tests for these variants are among the most commonly performed genetic tests (see previous news); however, their clinical utility has long been contested.

The study examined previously published data relating to the rates of VET among the family members of adult individuals with a knowna FVL or prothrombin G20210A mutation, and whether the testing of adults with VTE for these mutations improved their clinical outcomes [Segal JB et al. (2009) JAMA. 2009 301(23):2472-85]. The presence of one or two FVL alleles was found to be predictive of recurrent VTE for individuals and their family members (compared with VTE patients without the FVL mutation). However, heterozygosity for the relatively rare prothrombin G20210A mutation was not found to be predictive of recurrent VTE, and there was insufficient evidence to determine whether homozygosity for this mutation was predictive of recurrent VTE.

Lack of evidence was a general problem; the reviewers concluded that there was good evidence to support the assertion that treatment with anticoagulants (such as warfarin) reduced the probability of recurrent VTE in individuals with previous VTE and an identified FVL orprothrombin G20210A mutation. There was weaker evidence suggesting that the benefit was similar to that in individuals with previous VTE but no such mutations. However, there were no studies that assessed whether genetic testing for FVL or prothrombin G20210A in family members of those individuals improved outcomes in terms of reducing their risk of developing VTE.

Comment: Referring to the research, AHRQ Director Carolyn Clancy commented: “While genetic testing shows great promise to improve treatment and prevent disease, this report clearly shows that we need more research and evidence to achieve its full potential" (see press release). However, whether in fact genetic testing for either the FVL or prothrombin G20210A mutations has any clinical benefit at all even in VTE patients remains non-proven, let alone in family members. The authors suggest rather hopefully that If testing is done in conjunction with education, it may increase knowledge about risk factors for VTE”, but more practically call for prospective randomized trials to reliably determine whether or not testing has any influence on clinical outcomes. Meanwhile, millions of genetic tests for FVL are performed worldwide annually – perhaps not the best example of evidence-based genetic medicine.

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