The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group recently issued recommendations opposing routine genetic testing for factor V Leiden (FVL) and prothrombin (PT) mutations for those with deep vein thrombosis (DVT) or pulmonary embolism (PE) when there is no underlying cause. This also applies to their adult family members when there is no history or symptoms related to DVT/PE. The full recommendations are included in pdf file – click here.
NBCA asked Elizabeth Varga (a genetic counselor and member of NBCA’s Medical and Scientific Advisory Board) for her perspective, which follows:
I applaud the EGAPP Working Group for publishing recommendations regarding routine testing for Factor V Leiden and prothrombin G20210A. Despite the availability of several professional guidelines and expert opinion articles, a thorough review examining the clinical utility of testing was sorely needed.
These recommendations will be extremely helpful to practitioners who are trying to make a decision about routine thrombophilia workups in the context of idiopathic VTE. It is clear that there is limited evidence to support testing of patients, or their asymptomatic relatives, on a routine basis. However, it is important to keep the limitations of these guidelines in mind.
The authors acknowledge that their recommendations do not extend to patients with other risk factors for thrombosis, for example, a person with thrombosis in the setting of a transient risk factor (like oral contraceptive use). In this case, the patient might be treated with anticoagulation for 3 months; however, if homozygosity or compound heterozygosity for thrombophilia were found, this could impact decisions about duration of anticoagulation due to elevated recurrence risks. Secondly, the authors conclude that asymptomatic adult family members should not be screened since potential benefits are unlikely to exceed potential harms. The discussion is primarily based on weighing the risks of anticoagulation against the risk of developing a VTE. However, most practitioners recognize that intervention (with anticoagulation) would be required in only select high-risk scenarios (such as following surgery, long-distance travel, pregnancy that includes bedrest and possibly a C-section etc.). As the authors acknowledge, data examining the benefits of this type of short-term intervention during high-risk periods in patients with thrombophilia is quite limited, making it difficult to draw conclusions about efficacy. Furthermore, the authors do not consider the fact that non-anticoagulation based interventions (such as use of compression hose or intermittent compression devices) may be useful in preventing VTE in at-risk individuals, and these pose little harm.
Finally, what is missing in any evidence-based guideline, are the psychological and social aspects of thrombophilia testing. As a practicing genetic counselor with an interest in thrombophilia, and a past-Board member of NBCA, I have been exposed to both the benefits and harms that can arise from thrombophilia testing. There are cases of both under- and over-utilization of anticoagulation following a diagnosis of thrombophilia in patients or their relatives; there are stories of people being told not to have children after being labeled with a thrombophilia, because it was felt the risk of clotting in pregnancy would be too great; people have been denied oral contraceptives, and having their life insurance premiums elevated after learning the result. On the other hand, there are stories of empowerment. Even without an effective “treatment” being available, many people feel empowered knowing that they can educate themselves about signs and symptoms of VTE, and have a higher index of suspicion if symptoms arise. This knowledge may be life saving if appropriately applied.
In summary, although these recommendations are very useful in providing guidance about the use and need for routine testing in every case of idiopathic VTE and asymptomatic family member, the limitations of the guidelines need to be considered, and they should not be interpreted as a blanket statement condemning FVL or prothrombin testing. In the end, there may be specific subgroups of patients and their family members who may benefit from testing, after the implications for an individual patient and their family members have been considered. This underscores the importance of individualized counseling that should be provided before genetic testing to ensure that patients have an adequate understanding of the implications of a positive, as well as a negative test. These guidelines should be useful in informing this education process.