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

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.

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.

Complications

Although the most feared complication of DVT is fatal PE, DVT damages venous valves, causing venous insufficiency. Venous insufficiency, in turn, manifests as a spectrum ranging from painless varicosities to severe postphlebitic syndrome, which can cause unremitting pain and swelling, varicose veins, skin changes, and nonhealing ulcers. Figure 88-1 shows the leg of a construction worker with a femoral DVT that produces swelling on the job, impairing his ability to work.

Figure 88-1 Patient with moderate post-thrombophlebitic syndrome in the left leg several months after diagnosis with a common femoral deep vein thrombosis. Observe the swollen appearance and slight color change in the foot.

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.