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.
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.
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 can be seen in PE. The electrocardiogram can show an S1Q3T3 sign in PE, but that finding is not frequently observed.
Venous ultrasonography can detect DVT by demonstrating loss of normal venous compressibility. For pts with nondiagnostic venous ultrasound studies, CT or MRI can be used to assess for DVT. About one-half of pts with PE have no imaging evidence for DVT.
In PE, a normal chest x-ray (CXR) is common. Although not commonly observed, focal oligemia and peripheral wedge-shaped densities on CXR are well-established findings in PE. Chest CT with IV contrast has become the primary diagnostic imaging test for PE. Ventilation-perfusion lung scanning is primarily used for subjects unable to tolerate IV contrast. Transthoracic echocardiography can identify right ventricular hypokinesis with moderate to large PE, but it is not typically useful for diagnosing the presence of a PE. Transesophageal echocardiography can be used to identify large central PE when IV contrast chest CT scans are not appropriate (e.g., renal failure or severe contrast allergy). With the advent of contrast chest CT scans for PE diagnosis, pulmonary angiography studies are rarely performed.
Integrated Diagnostic Approach 
An integrated diagnostic approach that considers the clinical suspicion for DVT and PE is required. For individuals with a low clinical likelihood of DVT or with a low-to-moderate clinical likelihood of PE, the D-dimer level can be used to determine if further imaging studies are required. An algorithm for imaging studies in both DVT and PE is shown in Fig. 133-1. The differential diagnosis of DVT includes a ruptured Baker's cyst and cellulitis. The differential diagnosis of PE is broad and includes pneumonia, acute myocardial infarction, and aortic dissection.
Treatment: Deep-Vein Thrombosis and Pulmonary Thromboembolism ANTICOAGULATION Although anticoagulants do not dissolve existing clots in DVT or PE directly, they limit further thrombus formation and allow fibrinolysis to occur. Three general approaches can be used for anticoagulation in DVT and PE: (1) Parenteral therapy with transition to warfarin; (2) parenteral therapy with transition to an oral anticoagulant such as dabigatran or edoxaban; or (3) oral anticoagulation with rivaroxaban or apixaban without parenteral anticoagulation. Traditionally, intravenous unfractionated heparin (UFH) has been used, with a target activated partial thromboplastin time (aPTT) of 60-80 s. UFH is typically administered with a bolus of 80 U/kg followed by a continuous infusion of approximately 18 U/kg per hour. Frequent dosage adjustments are often required to achieve and maintain a therapeutic aPTT with UFH. Heparin-induced thrombocytopenia can occur with UFH. However, the short half-life of UFH remains a significant advantage. Alternatives to UFH for acute anticoagulation include low-molecular-weight heparins (LMWHs) such as enoxaparin and dalteparin. Laboratory monitoring is not required, but doses are adjusted for renal impairment or obesity. Fondaparinux, a synthetic parenteral alternative to UFH, does not require laboratory monitoring but does require dose adjustment for body weight and renal insufficiency. In pts with heparin-induced thrombocytopenia, direct thrombin inhibitors (e.g., argatroban or bivalirudin) should be used. After initiating treatment with a parenteral agent, warfarin is typically used for long-term oral anticoagulation. Warfarin can be initiated soon after a parenteral agent is given; however, at least 5 days are required for warfarin to achieve therapeutic anticoagulation. Warfarin is given to achieve a therapeutic international normalized ratio (INR) of the prothrombin time, which is typically an INR of 2.0-3.0. Pts vary widely in their required warfarin doses due to effects of genetics, diet, and other drugs; dosing often begins at 5 mg/d, with adjustment based on the INR. Novel oral anticoagulants, including rivaroxaban, apixaban, and dabigatran, have the advantages of fixed dose regimens, rapid onset of effective anticoagulation, no laboratory monitoring, and fewer drug and dietary interactions. However, anticoagulation with these Factor Xa or thrombin inhibitors is not readily reversed (with the exception of dabigatran, which has been shown in one study to be reversed by idarucizumab [Pollack C et al., N Engl J Med 2015;373:511-520]). The most troublesome adverse event from anticoagulation treatment is hemorrhage. For severe hemorrhage while undergoing treatment with UFH or LMWH, protamine can be given to reverse anticoagulation. Severe bleeding while anticoagulated with warfarin can be treated with prothrombin complex concentrate; milder hemorrhage or markedly elevated INR values can be treated with vitamin K. Warfarin should be avoided in pregnant pts. The duration of anticoagulation for an initial DVT or PE is at least 3-6 months. Pts with DVT or PE in the setting of trauma, surgery, indwelling central venous catheters, or high estrogen states have a low recurrence rate after 3-6 months of anticoagulation. However, recurrence rate is high in pts with cancer or with idiopathic, unprovoked DVT or PE, and prolonged anticoagulation should be considered. Recurrent DVT or PE typically requires lifelong anticoagulation. Other Treatment Modalities Although anticoagulation is the mainstay of therapy for venous thromboembolism, additional therapeutic modalities also can be employed, based on risk stratification (Fig. 133-2). Inferior vena cava filters can be used if thrombosis recurs despite adequate anticoagulation or if active bleeding precludes anticoagulation. Fibrinolytic therapy (often with tissue plasminogen activator) should be considered for PE causing right heart failure, although the risk of hemorrhage is significant. Surgical or catheter embolectomy also can be considered for massive PE. Low-dose, catheter-directed thrombolysis can be used for pts with extensive femoral, iliofemoral, or upper extremity DVT. If PE pts develop chronic thromboembolic pulmonary hypertension, surgical intervention (pulmonary thromboendarterectomy) can be performed. To reduce the severity of postthrombotic syndrome, below-knee graduated compression stockings can be used for 2 years after a DVT. Prevention of DVT and PE in hospitalized pts is often performed with low-dose UFH or LMWH. After cancer surgery or hip or knee replacement operations, pharmacological prophylaxis is usually performed for at least 4 weeks. |
For a more detailed discussion, see Goldhaber SZ: Deep Venous Thrombosis and Pulmonary Thromboembolism, Chap. 300, p. 1631, in HPIM-19. |
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