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Venous thromboembolism (VTE) is a common and serious disorder that includes deep venous thrombosis (DVT) and pulmonary embolism (PE). Patients presenting with VTE often have one or more risk factors for thromboembolism. Classic symptoms of a DVT include unilateral pain, swelling, erythema, and tenderness usually of the lower extremity; although some patients may be symptom free. Compression ultrasound is typically used to diagnose a DVT. The symptoms of a PE are nonspecific and may include chest pain, shortness of breath, tachypnea, dyspnea, and hemoptysis. Most PEs originate from a DVT. The diagnosis of a PE is made by the presence of symptoms in conjunction with findings on ventilation-perfusion (V/Q) and computerized tomography (CT) scans. Medical work-up of patients presenting with VTE include determination of risk factors for VTE. Certain risk factors are reversible (eg, estrogen use, recent orthopedic surgery, smoking, prolonged immobility) and may be eliminated over time. The presence of irreversible or continuing risk factors (eg, cancer, thrombophilia, previous history of VTE) requires longer or an extended duration of therapy.

Key Definitions

Anticoagulation—the process of preventing blood clot formation

Deep venous thrombosis (DVT)—blood clot formation in a deep vein, usually in the leg (eg, iliac vein)

Postphlebitic syndrome—chronic condition occurring after DVT characterized by venous insufficiency, pain, edema, stasis dermatitis, varicose veins, and ulceration

Pulmonary embolism (PE)—blockage of a pulmonary artery, usually from a thrombus that has traveled from another site, such as the deep vein of the leg

Thromboembolism—occlusion of a blood vessel due to a blood clot that has broken away and traveled from its place of origin

Thrombophilia—genetic or acquired predisposition to thrombosis

Thrombosis—pathologic blood clot formation


The goals of treatment in the management of VTE include preventing complications, such as thrombus extension, PE formation, VTE recurrence, mortality, and postphlebitic syndrome. Anticoagulants are the primary drug therapy used to achieve these goals and may be classified by basic mechanism of action into three groups: (1) indirect thrombin inhibitors, (2) direct thrombin inhibitors (DTIs), and (3) vitamin K antagonists. Both parenteral and some oral indirect thrombin inhibitors may be used for initial treatment of VTE. In most cases, patients receiving initial treatment with parenteral agents are transitioned to an oral anticoagulant for extended or indefinite therapy. In addition to treatment of VTE, anticoagulants are also used short and long term to prevent thromboembolic events, including those associated with cardiac valve replacement and myocardial infarction; thromboembolic stroke prevention related to atrial fibrillation, and VTE prevention in hospitalized or surgical patients at increased risk of thrombosis.


Indirect Thrombin Inhibitors

Heparin, low molecular weight heparins (LMWH), and factor Xa inhibitors comprise the commercially available indirect thrombin inhibitors (Table 7-1). These agents mediate their anticoagulant effect by activating antithrombin, an inhibitor of activated clotting factors, or directly inhibiting factor Xa.


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