Pulmonary Embolism and Deep Vein Thrombosis

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Chapter 88

Pulmonary Embolism and Deep Vein Thrombosis


This chapter discusses the diagnosis and treatment of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), from the perspective of the emergency physician and provides a functional resource for the evaluation and treatment of VTE in the emergency department (ED).

Deep Vein Thrombosis

DVT represents a disease spectrum ranging from a minimally symptomatic isolated calf vein thrombosis to a limb-threatening iliofemoral venous obstruction. Although the true incidence is unknown in the ED population, DVT accounts for approximately 600,000 hospital admissions per year.


The venous anatomy of the lower extremity is divided into the deep and superficial systems. The superficial venous system consists primarily of the greater and short saphenous veins and the perforating veins. The deep venous system includes the anterior tibial, posterior tibial, and peroneal veins, collectively called the calf veins. The calf veins join together at the knee to form the popliteal vein, which extends proximally and becomes the femoral vein at the adductor canal. The femoral vein sometimes is called the superficial femoral vein, and this nomenclature contributes to confusion in interpreting radiology reports. A clot in the superficial femoral vein is indeed a DVT and should be treated as such. The femoral vein joins with the deep femoral vein to form the common femoral vein, which subsequently becomes the external iliac vein at the inguinal ligament. Proximal DVT refers to a clot in the popliteal vein or higher, whereas distal clot refers to an isolated calf vein thrombosis.

Clinical Presentation

The initial symptoms of DVT can be as subtle and nonspecific as a mild cramping sensation or sense of fullness in the calf, without objective swelling, and may be difficult to differentiate clinically from myriad other, unrelated disorders (Box 88-1). Many patients use the term charley horse to describe the sensation of an early DVT. It is precisely at this early stage, however, that DVT can be treated most effectively to minimize the potential morbidity and mortality associated with VTE. Because the left iliac vein is vulnerable to compression by the left iliac artery, leg DVT occurs with a slightly higher frequency in the left leg compared with the right; bilateral leg DVT is found in fewer than 10% of ED patients diagnosed with DVT. Likewise, the clinical signs of DVT vary and may include unilateral swelling, edema, erythema, and warmth of the affected extremity; tenderness to palpation along the distribution of the deep venous system; dilation of superficial collateral veins; and a palpable venous “cord.” The classic Homan’s sign (pain felt in the calf or posterior aspect of the knee on passive dorsiflexion of the foot while the knee is extended) is insensitive and nonspecific for DVT and has no role in clinical assessment of the patient. Upper extremity DVT refers to a thrombosis in the axillary vein and causes arm swelling on the same side as an indwelling catheter or recent intravenous infusion site. In the absence of a catheter, the most frequent location of arm DVT is on the dominant hand side. Patients frequently note that their rings become tight as an early sign of DVT.


Diagnosis of DVT and PE starts with an estimation of the pretest probability (PTP). This estimation may be accomplished either by the clinical gestalt of an experienced practitioner or in conjunction with a clinical decision tool, such as that derived and validated by Wells and colleagues (Table 88-1). Patients with a low PTP can have DVT excluded with a normal quantitative D-dimer.

Table 88-1

Clinical Model for Estimating the Pretest Probability of Deep Vein Thrombosis


*A score of <2 indicates that the probability of deep vein thrombosis is low.

Adapted from Wells PS, Anderson D, Bormanis J: Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 350:1795, 1997.

Laboratory Evaluation

The D-dimer is a protein derived from enzymatic breakdown of cross-linked fibrin, and an elevated plasma concentration indicates the presence of a clot formed somewhere in the body within the previous 72 hours. D-dimer concentration may be elevated with any condition that causes fibrin deposition, including malignancy, pregnancy, advanced age, prolonged bed rest, recent surgery, infection, inflammation, new indwelling catheters, stroke, and myocardial infarction. D-dimer concentration is proportionate to the size of the clot and decreases as the clot matures, so the test is less sensitive with small or chronic clots.

The D-dimer protein can be measured in plasma with several techniques, and the differences in D-dimer assay methodology greatly affect diagnostic accuracy. All commercially available assays share the concept of antibody capture followed by detection. The U.S. Food and Drug Administration (FDA) has approved over 75 different D-dimer assays for clinical use. One way to categorize the D-dimer assay format is as quantitative or qualitative (which includes semiquantitative assays). The two most common detection methods for quantitative assays are the enzyme-linked immunosorbent assay (ELISA) and the immunoturbidimetric technique. Because of variable properties of the test capture antibody and differences in test standardization, their cutoffs for the upper limit of normal vary for different quantitative D-dimer assays. For many assays, less than 500 ng/mL (or 1000 fibrinogen equivalent units ([FEUs]) is a negative test result and carries an 88 to 97% diagnostic sensitivity for symptomatic proximal DVT and 83 to 94% sensitivity for calf DVT or asymptomatic proximal DVT. A negative quantitative D-dimer assayed by the ELISA or immunoturbidimetric technique is sensitive enough to exclude the diagnosis of DVT in patients at low or moderate risk without further evaluation.

Qualitative D-dimer assays include whole-blood assays done on single-use cartridges that resemble home pregnancy tests and semiquantitative, manual latex fixation assays that use test cards containing several wells for plasma in various folds of dilution (note that latex fixation assays have lower sensitivity than automated latex agglutination assays). Because qualitative D-dimer assays have a diagnostic sensitivity of only 78 to 93% for symptomatic proximal DVT, a negative qualitative D-dimer excludes proximal DVT only in patients deemed to have a low clinical possibility by the physician.

Radiographic Evaluation

DVT evaluation is by a combination of D-dimer testing and duplex venous ultrasonography.

Venous duplex ultrasonography, performed by a certified sonographer and interpreted by a board-certified radiologist or similarly credentialed expert, has a sensitivity and specificity of approximately 95% for proximal DVT and is the diagnostic test of choice in most centers. It is important for emergency physicians to know the technique of the examination. Most radiology departments use the three point sequence (common and superficial femoral veins and popliteal vein, excluding the calf and saphenous veins). Although management of calf vein and saphenous clots remains controversial, the diagnostic sensitivity of a single venous ultrasound for the exclusion of a clot at risk of progressing to a proximal DVT is increased significantly by including the calf and saphenous veins. A patient at low risk may have the diagnosis of DVT effectively excluded by a negative three-point venous duplex ultrasound. However, for patients at higher than low risk, a single negative three-point ultrasound is inadequate as a sole method to exclude DVT, whereas a single normal whole-leg ultrasound (including normal calf and saphenous veins) is sufficient to exclude DVT with any PTP.1 A negative three-point ultrasound together with a negative quantitative D-dimer is sufficient to exclude DVT with any PTP. In a patient with a high PTP in whom the D-dimer is elevated (or not performed), a negative three-point ultrasound at the index visit should be followed by a repeat ultrasound in 2 to 7 days, which if negative is sufficient to exclude PE. An expertly performed and interpreted positive ultrasound is sufficient to confirm the diagnosis of DVT. Ultrasound cannot be used to rule out iliac or pelvic vein thrombosis.

Many emergency physicians use bedside ED ultrasound in their daily practice, but at present the data are conflicting as to whether emergency physician–performed ultrasound (EPPU) for lower-extremity DVT has adequate diagnostic accuracy. Follow-up with formal diagnostic duplex ultrasound seems reasonable.2

Indirect computed tomography (CT) venography (CTV) is not a primary imaging modality for DVT but may be performed in conjunction with CT pulmonary angiography (CTPA) of the chest during the evaluation of suggested PE. Adding CTV to CTPA provides an incremental increase in the sensitivity for VTE, identifying DVT in approximately 2% of patients in whom the CTPA is read as negative for PE but at the expense of significant additional radiation exposure to the pelvis and lower extremities.3 Interobserver agreement among radiologists interpreting CTV appears to be less than that for the CTPA portion of the study, possibly because of poor venous opacification in many cases.4 At this time, routine use of CTV is not necessary when CTPA is performed.11

Magnetic resonance imaging (MRI) can evaluate the pelvic vasculature and vena cava, which is not possible with ultrasound. MRI does not produce ionizing radiation, making it an attractive option for pregnant patients but limited by cost, availability, patient size, and tolerance to close quarters. MRI is not a primary diagnostic test for patients with suspected DVT.


When the diagnosis of DVT has been established, anticoagulation should be initiated, unless contraindicated, with a low-molecular-weight heparin (e.g., enoxaparin 1 mg/kg subcutaneously [SQ] every 12 hours), fondaparinux (5-10 mg SQ once daily, depending on patient weight), or unfractionated heparin (70-80 units/kg intravenous bolus followed by 17-18 units/kg/hr infusion), assuming normal renal function. The treatments work equally well and are safe in the absence of contraindications to anticoagulation. Treatment requires transition to oral anticoagulation with warfarin for at least 3 months. Hospital admission is obviated by initiation of outpatient low-molecular-weight heparin or fondaparinux therapy in the ED or ED observation unit, followed by self-administration at home (with appropriate patient teaching) or home administration by a visiting nurse. If admission is contemplated, after heparin has been given, the first dose of warfarin can be given in the ED to help reduce overall length of stay in the inpatient unit. Patients should be encouraged to ambulate after anticoagulation for DVT. Bed rest promotes DVT extension, increases the risk of embolization, and ultimately predisposes the patient to the postphlebitic syndrome. Patients who cannot be given anticoagulants or who have a recurrence of VTE despite anticoagulation therapy should be considered for vena caval intervention.

Superficial Leg Thrombophlebitis

Based on the results of a large randomized controlled trial, patients with a clot in the greater saphenous vein that extends above the knee are at risk for progression to DVT via the saphenous-femoral vein junction and may require an abbreviated course of anticoagulation.5 The published evidence suggests that saphenous vein thrombophlebitis can adequately be treated with nonsteroidal anti-inflammatory drugs, heat, and graded compression stockings (fitted to exert 30-40 mm Hg of pressure at the ankle) followed by a mandatory repeat ultrasound in 2 to 5 days. If the clot is extending, then anticoagulation is indicated. The duration of anticoagulation treatment remains uncertain, but full-dose low molecular weight heparin or fondaparinux for 10 days followed by repeat ultrasound seems reasonable.

Isolated Calf Vein Thrombosis

The optimal management strategy for thromboses of the tibial or peroneal veins remains controversial.7 Approximately 25% of isolated calf vein thromboses propagate proximally, prompting recommendations for treatment with anticoagulation as for proximal leg DVT.8 However, most of these data were from hospitalized or postoperative patients with a higher risk of propagation than ambulatory patients.9 For tibial or peroneal vein thrombosis in an otherwise healthy, ambulatory patient with no other indication for anticoagulation, I recommend antiplatelet therapy with aspirin (325 mg of enteric-coated acetylsalicylic acid per day) and close follow-up with repeat duplex ultrasound scan at 2 to 5 days to evaluate for clot propagation.

Phlegmasia Cerulea Dolens (Painful Blue Leg)

Massive iliofemoral occlusion results in swelling of the entire leg with extensive vascular congestion and associated venous ischemia, producing a painful, cyanotic extremity. There may be an associated arterial spasm resulting in phlegmasia alba dolens (painful white leg or milk leg), which may mimic an acute arterial occlusion. Prompt consultation with a vascular surgeon should be obtained because patients with phlegmasia cerulea dolens may require emergent thrombectomy. If timely consultation is not possible, early thrombolytic therapy may be a limb-salvaging procedure in the absence of contraindications. One strategy is to infuse alteplase (1 mg/min to a total dose of 50 mg) via a peripheral intravenous catheter placed distal to the thrombus.

Upper Extremity Venous Thromboses

DVTs of the upper extremity have become more common in association with increased use of indwelling venous catheters and wires for electronic cardiac devices. Upper extremity DVT can cause PE, and all patients with DVT above the elbow require definitive treatment.10–12

About one half of all upper extremity DVTs are associated with an indwelling catheter. Upper extremity DVT is diagnosed and excluded with venous ultrasound. The use of D-dimer testing in this population is inadequately studied.

In the absence of pain or infection, catheter-associated DVT does not automatically warrant catheter removal if the catheter serves a current, vital purpose. However, these patients should receive anticoagulation if they do not have contraindications. The duration of anticoagulation after catheter removal for DVT remains controversial, but most published guidelines recommend at least 3 months.

The rate of PE from axillary vein DVT appears to be similar to that for femoral vein DVT, although many experts believe the severity of PE tends to be less with upper extremity DVT.

Isolated upper extremity DVT, especially axillary-subclavian vein thrombosis, also can be seen in relatively young, active, otherwise healthy patients. Although standard DVT risk factors, such as hypercoagulable state or malignancy, may be present, most of these patients have no apparent predisposing condition. Some patients with arm DVT have inherited or acquired subclavian vein stenosis or extrinsic compression. It is not known whether strenuous, repetitive activity (“effort DVT”) causes the DVT by exacerbating the anatomic compromise through movement of the arm or hypertrophy of adjacent muscles, or whether effort simply brings out the symptoms of an otherwise occult upper extremity DVT. Optimal treatment of isolated brachial vein thrombosis, often the result of a recent intravenous infusion (“infusion phlebitis”), also remains uncertain. No study has demonstrated clear benefit for systemic anticoagulation, but a good strategy is to use the same management plan as described for superficial thrombophlebitis of the leg.

Pulmonary Embolism

PE results from a clot that formed hours, days, or weeks earlier in the deep veins and dislodged, traveled through the venous system, and traversed the right ventricle into the pulmonary vasculature. What the patient experiences during this process varies widely, ranging from no symptom to cardiovascular collapse. No one knows exactly how many patients pass through the ED with PE because there is no reliable way of identifying missed cases. Assuming that ED populations have a risk for PE somewhere between that of hospitalized patients (who are at high risk for PE) and outpatients (who are at lower risk), approximately 1 in every 500 to 1000 ED patients has PE. About 8% of ED patients with PE die within 30 days, even when PE is promptly diagnosed and treated.10

Pathophysiology of Pulmonary Vascular Occlusion

The pulmonary vascular tree normally has a low resistance to fluid flow, and young persons without cardiopulmonary disease (e.g., congestive heart failure, chronic obstructive lung disease, advanced sarcoidosis, pulmonary fibrosis, scleroderma, and primary pulmonary hypertension) can tolerate at least 30% obstruction, often with minimal symptoms or signs. Pulmonary infarction is a more dramatic exception. Although a segmental pulmonary artery constitutes only about one sixteenth of the entire pulmonary vascular circuit, a clot lodged deeply in a segmental artery can obstruct blood flow to a sufficient degree to cause tissue necrosis. The patient can feel focal, sharp, pleuritic pain and exhibit a splinting response to breathing. Over several days the infarcted segment becomes consolidated on chest radiography and exudes a pleural effusion, manifesting an intense underlying inflammatory process. Chest pain from noninfarcting PE can be highly variable and vague. About 30% of patients with definite PE have no perception of chest pain.

In contrast, if asked in a detailed and structured way, about 90% of patients with noninfarcting emboli admit to the sensation of dyspnea. The dyspnea may be constant and oppressive or may be intermittent and perceived only with exertion, possibly because of an exercise-induced increase in pulmonary vascular resistance. Rest dyspnea seems to be the clinical manifestation of distorted and irregular blood flow within the lung, referred to as ventilation-perfusion inequality. With each breath a patient with PE wastes ventilation because of increased alveolar dead space (alveoli that are ventilated but not perfused). A lodged clot can redistribute blood flow to areas of the lung with already high perfusion relative to ventilation and therefore cause more blue blood to pass through the lung without being fully oxygenated. This venous admixture is probably the primary cause of hypoxemia with PE and the increased alveolar-arterial oxygen difference (the A-a gradient). About 15% of patients with PE have a normal A-a gradient of oxygen (with normal defined as age in years/4 + 4), however, and the A-a gradient is abnormally high in most patients who are evaluated for PE but ultimately found to not have PE. In a multicenter registry of 348 patients with PE, 37 (10.6%) had a pulse oximetry reading of 100% at the time of arrival to the ED, while breathing room air. Despite its shortcomings as a single diagnostic step, the presence of hypoxemia (pulse oximetry <95%, breathing room air) that cannot be explained by a known disease process increases the probability of PE. Conversely, a normal oxygen saturation can be used only when considered together with multiple other clinical features and should not alone or independently be used to forego testing for PE (Box 88-2).18,19 In addition, when PE is diagnosed, the severity of hypoxemia represents a powerful independent predictor of patient outcome.

PE also causes highly variable effects on vital signs. In the ED, about half of all patients with PE have a heart rate greater than 100 beats/min.11 Tachycardia from PE probably results from impaired left ventricular filling, leading to a pathophysiologic process that parallels that of hemorrhagic shock. In one study, the probability of PE was not reduced in patients who normalized any vital sign while in the ED.12 When PE obstructs more than 50% of the vasculature, it usually causes an acute increase in right ventricular pressure. In contrast to the left ventricle, the right ventricle does not show an elastic response to acutely increased afterload; it quickly dilates, showing echocardiographic hypokinesis early in the course. In about 40% of cases, the right ventricular damage persists for at least 6 months and probably longer. Arterial hypotension represents an ominous hemodynamic consequence of PE; it occurs in only about 10% of patients but signifies a fourfold increase in risk of death compared with normotensive patients.20 In its most extreme form, PE can obstruct the right ventricular outflow entirely, either by casting the entire pulmonary vascular tree (Fig. 88-2) or by acutely occluding the main pulmonary artery. Pulseless electrical activity (PEA) is the most common electrocardiogram (ECG) result from obstructive PE. The survival rate for cardiac arrest from PE is abysmally low, even if the arrest is witnessed and heroic treatment is initiated.

Clinical Presentation

Table 88-2 presents a listing of factors that significantly increase the probability of PE in the ED population.11

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