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Venous thromboembolism, consisting of deep vein thrombosis and/or pulmonary embolism, is a common disorder with an estimated 900,000 patients each year in the United States and more than 1 million each year in the European Union. Approximately one-third of these cases are fatal pulmonary emboli, and the remaining two-thirds are nonfatal episodes of symptomatic deep vein thrombosis or pulmonary embolism. The majority of fatal events occur as sudden death, underscoring the importance of prevention as the critical strategy for reducing death from pulmonary embolism. Of the nonfatal cases, approximately 60 percent present clinically as deep vein thrombosis and 40 percent present as pulmonary embolism. Most clinically important pulmonary emboli arise from proximal deep vein thrombosis of the leg (popliteal, femoral, or iliac vein thrombosis). Upper-extremity deep vein thrombosis also may lead to clinically important pulmonary embolism. The clinical features of deep vein thrombosis and pulmonary embolism are nonspecific. Objective diagnostic testing is required to confirm or exclude the presence of venous thromboembolism. A validated assay for plasma D-dimer, if available, provides a simple, rapid, and cost-effective first-line exclusion test in patients with low, unlikely, or intermediate clinical probability. Compression ultrasonography is highly sensitive and specific for clinically important deep vein thrombosis and is the primary imaging test for symptomatic patients. Compression ultrasonography of the proximal veins performed at presentation, and if normal, repeated once 5 to 7 days later, can safely exclude clinically important deep vein thrombosis. In centers with the expertise, a single comprehensive evaluation of the proximal and calf veins with duplex ultrasonography is sufficient. In patients with suspected pulmonary embolism, computed tomographic angiography, with or without additional testing using computed tomographic venography or compression ultrasonography of the legs, provides a definitive basis to give or withhold antithrombotic therapy in 90 percent of patients. Anticoagulant therapy is the preferred treatment for most patients with acute venous thromboembolism. Initial treatment with heparin or low-molecular-weight heparin, followed by long-term treatment with an oral vitamin K antagonist such as warfarin, is highly effective for preventing recurrent venous thromboembolism, and has been the traditional standard care. More recently, the direct oral anticoagulants including the thrombin inhibitor dabigatran, and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have been established to be as effective and safer than traditional standard anticoagulant therapy. Rivaroxaban and apixaban can be used as a single drug approach. Dabigatran and edoxaban are preceded by at least 5 days of heparin or low-molecular-weight heparin treatment. The direct oral anticoagulants are preferred over the vitamin K antagonists in most new patients commencing anticoagulant therapy. In cancer patients with venous thromboembolism, treatment with low-molecular-weight heparin for at least 6 months is the recommended approach. Thrombolytic therapy is indicated for patients with pulmonary embolism who present with hypotension or shock, and in selected patients who have impaired right ventricular function who are at high risk of hemodynamic collapse. Insertion of a vena cava filter is indicated for patients who have an absolute contraindication ...

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