Testing for inherited thrombophilia is controversial, with some arguing that these tests should never be performed. In the United States, thrombophilia testing is performed almost routinely, despite expert statements advising that such testing not be performed and data showing that the results should not alter venous thromboembolism (VTE) management. The first steps in deciding whether to test a patient are to determine why the tests are being ordered and how the results will be used. Read the latest Review Article.
Q: Why is thrombophilia testing controversial?
A: The controversy surrounding testing stems from the demonstrated lack of effect of thrombophilia status on VTE outcomes, including death. Available data show no significant differences in rates of recurrent VTE between patients with and those without thrombophilia or between patients who undergo testing for inherited thrombophilia and those who do not. The significance of either positive or negative test results is often misinterpreted in clinical practice. Patients with positive results are frequently overtreated and kept on anticoagulant therapy indefinitely, even those with a provoked VTE and a low risk of recurrence, because of the perception that such patients have a significantly increased risk of recurrence. In addition, current tests for inherited thrombophilia are insufficient for identifying inherited risks of VTE. Although positive test results might be useful for guiding decisions about testing first-degree family members who have not had VTE, patients and providers may falsely assume that the risk of VTE is low for family members with negative results.
Q: Are there any validated guidelines for thrombophilia testing?
A: No validated testing guidelines have been published. The American College of Chest Physicians does not give guidance on thrombophilia testing in its ninth edition of clinical practice guidelines for antithrombotic therapy or its 2016 VTE update, whereas the American Society of Hematology’s 2013 Choosing Wisely campaign recommends not testing for thrombophilia in adults with VTE who have major transient risk factors. According to the most comprehensive guide, Clinical Guidelines for Testing for Heritable Thrombophilia, published by the British Committee for Standards in Haematology, “It is not possible to give a validated recommendation as to how such patients (and families) should be selected” for testing. Although similar guidelines advise limiting testing to a narrow range of specific clinical situations and patients, the recommendations are not uniform.
Morning Report Questions
Q: If thrombophilia testing is undertaken in a patient with VTE, should it be done at the time of presentation?
A: It is not necessary to ascertain thrombophilia status at the time of presentation, even in patients who might benefit from such testing. Many tests ordered at the time of initial presentation, such as tests for protein C, protein S, antithrombin, and lupus anticoagulants, can have falsely low results because of acute thrombosis, inflammation, pregnancy or recent miscarriage, and other medical conditions. Patients should have completed anticoagulant therapy and should not be taking oral anticoagulants at the time of testing, since vitamin K antagonists will decrease protein S and protein C levels, and direct oral anticoagulants can affect clot-based assay results. Vitamin K antagonists should be withheld for a minimum of 2 weeks, and direct oral anticoagulants should be withheld for at least 5 half-lives, generally a minimum of 2 to 3 days.
Q: Is there a role for thrombophilia testing in young women who have a first degree relative with an inherited thrombophilia?
A: Exogenous estrogens and combination estrogen–progesterone oral contraceptives are associated with an increased risk of VTE among all women, with an additive and even synergistic increase in risk among women with inherited thrombophilias. The greatest anxiety and controversy regarding thrombophilia testing concerns young female patients contemplating estrogen use. Although studies have shown that it is not practical or cost-effective to screen all women for thrombophilia before they use combination oral contraceptives, for women who are first-degree relatives of patients with VTE and known inherited thrombophilia, screening may provide guidance in making informed choices about contraceptive use.
Figure 1. Algorithm for Selecting Patients with a First Venous Thromboembolism (VTE) for Thrombophilia Testing.
Table 2. Summary of Recommendations Regarding Testing for Thrombophilia.
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