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DEFINITION AND NATURAL HISTORY

Venous thromboembolism includes both deep-vein thrombosis (DVT) and pulmonary thromboembolism (PE). DVT results from blood clot formation within large veins, usually in the legs. PE results from DVTs that have broken off and traveled to the pulmonary arterial circulation. About one-half of pts with pelvic vein or proximal leg DVT develop PE, which is often asymptomatic. Isolated calf vein thrombi have much lower risk of PE. Although DVTs are typically related to thrombus formation in the legs and/or pelvis, indwelling venous catheters have increased the occurrence of upper extremity DVT. In the absence of PE, the major complication of DVT is postphlebitic syndrome, which causes chronic leg swelling and discomfort due to damage to the venous valves of the affected leg. In its most severe form, postphlebitic syndrome causes skin ulceration. PE is often fatal, usually due to progressive right ventricular failure. Chronic thromboembolic pulmonary hypertension is another long-term complication of PE.

Some genetic risk factors, including factor V Leiden and the prothrombin G20210A mutation, have been identified, but they account for only a minority of venous thromboembolic disease. A variety of other risk factors have been identified, including immobilization during prolonged travel, cancer, obesity, smoking, surgery, trauma, pregnancy, oral contraceptives, and postmenopausal hormone replacement. Medical conditions that increase the risk of venous thromboembolism include cancer and antiphospholipid antibody syndrome.

CLINICAL EVALUATION

History

DVTs often present with progressive lower calf discomfort. For PE, dyspnea is the most common presenting symptom. Chest pain, cough, or hemoptysis can indicate pulmonary infarction with pleural irritation. Syncope can occur with massive PE.

Physical Examination

Tachypnea and tachycardia are common in PE. Low-grade fever, neck vein distention, and a loud P2 on cardiac examination can be seen. Hypotension and cyanosis suggest massive PE. Physical examination with DVT may be notable only for mild calf tenderness. However, with massive DVT, marked thigh swelling and inguinal tenderness can be observed.

Laboratory Tests

Normal d-dimer level (<500 μg/mL by enzyme-linked immunosorbent assay) essentially rules out PE in pts with low-to-moderate likelihood of PE, although hospitalized pts often have elevated d-dimer levels due to other disease processes. Although hypoxemia and an increased alveolar-arterial O2 gradient may be observed in PE, arterial blood gases are rarely useful in diagnosing PE. Elevated serum troponin, plasma heart-type fatty acid-binding protein, and brain natriuretic peptide levels are associated with increased risk of complications and mortality in PE. The electrocardiogram can show an S1Q3T3 sign in PE, but that finding is not frequently observed.

Imaging Studies

Venous ultrasonography can detect DVT by demonstrating loss of normal venous compressibility. When combined with Doppler imaging of venous flow, the detection of DVT by ultrasonography is excellent. For pts with nondiagnostic venous ultrasound studies, CT or MRI can be used to assess for DVT. Contrast phlebography is very rarely required. About one-half of pts with PE have no imaging ...

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