Thrombophilia: How To Test? How To Manage?

By Julie Hambleton, MD

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Who To Test?

After a patient presents with an unprovoked DVT, many clinicians advocate evaluation for a genetic thrombophilic state. However, the utility of information gleaned from such an evaluation remains controversial.^12-14 The ultimate goals of testing are to elucidate why an individual patient developed VTE, define the patient's risk for recurrence, and implement an optimally effective and safe duration of therapy. Unfortunately, our knowledge of and insight into these disorders is insufficient to meet these goals currently. The available data do strongly suggest that individuals in whom lupus anticoagulant persists are at increased risk for both recurrent arterial and venous disease if therapy is discontinued.¹⁵ Thus, many advocate that all patients presenting with an unprovoked VTE event should be evaluated for the persistent presence of a lupus anticoagulant. Persons with AT deficiency who have had a DVT appear to be at increased risk for recurrence. This may also be true for deficiencies of PC and PS.¹⁶ However, the prevalence of these deficiencies is low and screening strategies are less likely to identify affected individuals. In contrast, individuals with the factor V Leiden and prothrombin mutations are more likely to be identified, but the data suggest that these individuals do not predictably experience recurrent VTE.¹¹ Individuals with double defects or homozygous states have a very high relative risk for recurrent VTE, but the prevalence of these two genetic conditions is uncommon.^11,17 Thus, only small numbers of these patients have been enrolled in clinical trials, making a determination of the absolute risk of recurrent disease elusive. Finally, the impact of hyperhomocysteinemia on recurrence among patients with minimal or moderate elevation is unclear, especially if the homocysteine level can be normalized with vitamin supplementation.

In summary, an increasing number of genetic mutations predispose individuals to venous thromboembolic disease. Detection of these inherited thrombophilic defects is not generally useful in guiding clinical decision making regarding the choice of anticoagulant therapy or the intensity and duration of therapy. Testing of asymptomatic or unselected individuals (those with a first episode) should be done by a clinician who can provide informed counseling on the limitations of testing and the impact on risk. Unfortunately, our tools to identify the majority of individuals who will develop recurrent disease are limited at present, and the identification of individuals who would benefit from long-term anticoagulant therapy remains a major clinical research objective.

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