The thrombophilias: Well-defined risk factors with uncertain therapeutic implications

Discovery of the factor V Leiden and prothrombin G20210A mutations has grea tly increased the percentage of patients in whom venous thrombosis can be a ttributed to hereditary thrombophilia. The first step in the diagnostic app roach to all patients with venous thrombosis consists of a careful history and physical examination combined with routine laboratory testing to charac terize 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 an d challenging issues to consider. Routine testing would be warranted if the identification of abnormalities l ed to an alteration in the type or duration of initial anticoagulant therap y 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 identifiabl e abnormalities. On the basis of relative prevalences of the various thromb ophilias, patients can be classified as "strongly" or "weakly" thrombophili c depending on their thrombotic histories. Management considerations and gu idelines are offered for patients who are found to have one or more defined abnormalities, hereditary or otherwise. The future identification of addit ional laboratory abnormalities predisposing patients to thrombosis, coupled with prospective clinical trials, should enable us to better identify pati ents at high risk for recurrence who will benefit from prolonged anticoagul ant prophylaxis.