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The Thrombophilias: Well-Defined Risk Factors with Uncertain Therapeutic Implications

Kenneth A. Bauer, MD
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From Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts.


Grant Support: In part by the Medical Research Service of the U.S. Department of Veterans Affairs.

Requests for Single Reprints: Kenneth A. Bauer, MD, Veterans Affairs Boston Healthcare System, 1400 VFW Parkway, West Roxbury, MA 02132; e-mail, kbauer@caregroup.harvard.edu.


Ann Intern Med. 2001;135(5):367-373. doi:10.7326/0003-4819-135-5-200109040-00013
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Discovery of the factor V Leiden and prothrombin G20210A mutations has greatly increased the percentage of patients in whom venous thrombosis can be attributed to hereditary thrombophilia. The first step in the diagnostic approach to all patients with venous thrombosis consists of a careful history and physical examination combined with routine laboratory testing to characterize the severity of the thrombotic condition and determine the presence of any of the acquired causes of hypercoagulability. The second step is to consider screening for the causes of hereditary and acquired thrombophilia in selected subsets of patients. The selection of patients for testing, the choice of tests to perform, and the timing of the testing are important and challenging issues to consider.Routine testing would be warranted if the identification of abnormalities led to an alteration in the type or duration of initial anticoagulant therapy or the use of long-term prophylactic anticoagulation. The available data, however, do not yet indicate that most patients with defined thrombophilic states should be managed any differently than patients without identifiable abnormalities. On the basis of relative prevalences of the various thrombophilias, patients can be classified as “strongly” or “weakly” thrombophilic depending on their thrombotic histories. Management considerations and guidelines are offered for patients who are found to have one or more defined abnormalities, hereditary or otherwise. The future identification of additional laboratory abnormalities predisposing patients to thrombosis, coupled with prospective clinical trials, should enable us to better identify patients at high risk for recurrence who will benefit from prolonged anticoagulant prophylaxis.

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