eMedicine Specialties > Pulmonology > Pulmonary Embolism
Pulmonary Embolism: Differential Diagnoses & Workup
Updated: Aug 25, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Differential diagnoses are extensive, and they should be considered carefully with any patient thought to have pulmonary embolism. These patients also should have an alternate diagnosis confirmed, or pulmonary embolism should be excluded, before discontinuing the workup. Additional problems to be considered include the following:
Musculoskeletal pain
Pleuritis
Costochondritis
Rib fracture
Pericarditis
Angina pectoris
Salicylate intoxication
Hyperventilation
Silicone pulmonary embolism12
Workup
Laboratory Studies
Clinical signs and symptoms for pulmonary embolism (PE) are nonspecific; therefore, patients suspected of having pulmonary embolism—because of unexplained dyspnea, tachypnea, or chest pain or the presence of risk factors for pulmonary embolism—must undergo diagnostic tests until the diagnosis is ascertained or eliminated or an alternative diagnosis is confirmed. Further, routine laboratory findings are nonspecific and are not helpful in pulmonary embolism, although they may suggest another diagnosis.
Evidence-based literature supports the practice of determining the clinical probability of pulmonary embolism before proceeding with testing.13 A clinical practice guideline from the American Academy of Family Physicians (AAFP) and the American College of Physicians (ACP) recommends that validated clinical prediction rules be used to estimate pretest probability of pulmonary embolism and to interpret test results.14,15 The guideline, Current diagnosis of venous thromboembolism in primary care, advocates use of the Wells prediction rule for this purpose, but notes that the Wells rule performs better in younger patients without comorbidities or a history of venous thromboembolism.
Table 1. Wells Prediction Rule for Diagnosing Pulmonary Embolism: Clinical Evaluation Table for Predicting Pretest Probability of Pulmonary Embolism
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Table
| Clinical Characteristic | Score |
| Previous pulmonary embolism or deep vein thrombosis | + 1.5 |
| Heart rate >100 beats per minute | + 1.5 |
| Recent surgery or immobilization (within the last 30 d) | + 1.5 |
| Clinical signs of deep vein thrombosis | + 3 |
| Alternative diagnosis less likely than pulmonary embolism | + 3 |
| Hemoptysis | + 1 |
| Cancer (treated within the last 6 mo) | + 1 |
| Clinical Characteristic | Score |
| Previous pulmonary embolism or deep vein thrombosis | + 1.5 |
| Heart rate >100 beats per minute | + 1.5 |
| Recent surgery or immobilization (within the last 30 d) | + 1.5 |
| Clinical signs of deep vein thrombosis | + 3 |
| Alternative diagnosis less likely than pulmonary embolism | + 3 |
| Hemoptysis | + 1 |
| Cancer (treated within the last 6 mo) | + 1 |
Note: Clinical probability of pulmonary embolism: low 0–1; intermediate 2–6; high >7
Reprinted from Am J Med, Vol 113, Chagnon I, Bounameaux H, Aujesky D, et al, Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism, pp 269-75, Copyright 2002.
Another validated clinical prediction rule for use in the diagnosis of pulmonary embolism is the revised Geneva score.16 The performance of the revised Geneva score appears equivalent to that of the Wells score.17
Table 2 The Revised Geneva Score*
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Table
| Risk Factors | Points |
| Age older than 65 y | 1 |
| Previous DVT or PE | 3 |
Surgery (under general anesthesia) or fracture (of the lower limbs) within 1 mo | 2 |
| Active malignant condition (solid or hematologic, currently active or considered cured <1 y) | 2 |
| Symptoms | |
| Unilateral lower limb pain | 3 |
| Hemoptysis | 2 |
| Clinical Signs | |
| Heart rate 75–94 beats/min | 3 |
| Heart rate ≥95 beats/min | 5 |
| Pain on lower limb deep venous palpation and unilateral edema | 4 |
| Clinical Probability | |
| Low | 0–3 total |
| Intermediate | 4–10 total |
| High | ≥11 total |
| Risk Factors | Points |
| Age older than 65 y | 1 |
| Previous DVT or PE | 3 |
Surgery (under general anesthesia) or fracture (of the lower limbs) within 1 mo | 2 |
| Active malignant condition (solid or hematologic, currently active or considered cured <1 y) | 2 |
| Symptoms | |
| Unilateral lower limb pain | 3 |
| Hemoptysis | 2 |
| Clinical Signs | |
| Heart rate 75–94 beats/min | 3 |
| Heart rate ≥95 beats/min | 5 |
| Pain on lower limb deep venous palpation and unilateral edema | 4 |
| Clinical Probability | |
| Low | 0–3 total |
| Intermediate | 4–10 total |
| High | ≥11 total |
Simplified versions of the Wells score and the revised Geneva score have been developed. Initial studies support the validity of these scores, which assign 1 point to each of the criteria.18,19
- D-dimer testing
- When clinical prediction rule results indicate that the patient has a low or moderate pretest probability of pulmonary embolism, D-dimer testing is the usual next step.13 Negative results on a high-sensitivity D-dimer test in a patient with a low pretest probability of pulmonary embolism indicate a low likelihood of venous thromboembolism and reliably exclude pulmonary embolism. A large prospective randomized trial found that in patients with a low probability of pulmonary embolism who had negative D-dimer results, forgoing additional diagnostic testing was not associated with an increased frequency of symptomatic venous thromboembolism during the subsequent 6 months.20
- D-dimer, a degradation product produced by plasmin-mediated proteases of cross-linked fibrin, is measured by a variety of assay types, including quantitative, semiquantitative, and qualitative rapid enzyme-linked immunosorbent assays (ELISAs); quantitative and semiquantitative latex; and whole-blood assays. A systematic review of prospective studies of high methodologic quality concluded that the ELISAs—especially the quantitative rapid ELISA—dominate the comparative ranking among the D-dimer assays for sensitivity and negative likelihood ratio.21 The quantitative rapid ELISA has a sensitivity of 0.95 and negative likelihood ratio of 0.13; the latter is similar to that for a normal to near-normal lung scan in patients with suspected pulmonary embolism.
- D-dimer testing is most reliable for excluding pulmonary embolism in younger patients who have no associated comorbidity or history of venous thromboembolism and whose symptoms are of short duration.14 D-dimer testing is of questionable value in patients who are older than 80 years, are hospitalized, or have cancer and in pregnant women, because nonspecific elevation of D-dimer concentrations is common in such patients. D-dimer test should not be used when the clinical probability of pulmonary embolism is high, because the test has low negative predictive value in such cases.22
- Troponins
- Serum troponin levels can be elevated in up to 50% of patients with a moderate-to-large pulmonary embolism, presumptively due to acute right ventricular myocardial stretch.23
- Although not currently recommended as part of the diagnostic workup, studies have shown that elevated troponin levels in the setting of pulmonary embolism correlate with increased mortality.24 Currently, further studies need to be performed to identify subsets of patients with pulmonary embolism who might benefit from this testing.
- Brain natriuretic peptide
- Although neither sensitive nor specific, patients with pulmonary embolism tend to have higher levels of brain natriuretic peptide (BNP). In one case-control study of 2213 hemodynamically stable patients with suspected acute pulmonary embolism, BNP testing had a sensitivity and specificity of only 60% and 62%, respectively.25
- Elevated levels of BNP or its precursor, N -terminal pro-brain natriuretic peptide (NT-proBNP), do correlate with an increased risk of subsequent complications and mortality in patients with acute pulmonary embolism. One meta-analysis revealed that patients with a BNP level greater than 100 pg/mL or an NT-proBNP level greater than 600 ng/L had an all-cause in-hospital mortality rate 6- and 16-fold higher than those below these cutoffs, respectively.26 In a second smaller observational study, serum BNP levels greater than 90 pg/mL were associated with a higher rate of complications, such as the need for cardiopulmonary resuscitation, need for mechanical ventilation, need for vasopressor therapy, and death.27
- BNP testing is not currently recommended as part of the standard evaluation of acute pulmonary embolism, and future studies may aid in defining its role in this setting.
- Arterial blood gases
- Arterial blood gas determinations characteristically reveal hypoxemia, hypocapnia, and respiratory alkalosis; however, the predictive value of hypoxemia is quite low.
- Both the PaO2 and the calculation of alveolar-arterial oxygen gradient contribute to the diagnosis in a general population thought to have pulmonary embolism.
- Nonetheless, in high-risk settings such as patients in postoperative states in whom other respiratory conditions can be ruled out, a low PaO2 in conjunction with dyspnea may have a strong positive predictive value.
Imaging Studies
- Chest radiography
- The American College of Radiology (ACR) recommends chest radiography as the most appropriate study for ruling out other causes of chest pain in patients with suspected pulmonary embolism.28
- Initially, the chest radiography findings are normal in most cases of pulmonary embolism. However, in later stages, radiographic signs may include a Westermark sign (dilatation of pulmonary vessels and a sharp cutoff), atelectasis, a small pleural effusion, and an elevated diaphragm.
- Although chest radiography findings may indicate an alternate diagnosis, this study alone is not sufficient to confirm the diagnosis of pulmonary embolism.
Posteroanterior and lateral chest radiograph findings are normal, which is the usual finding in patients with pulmonary embolism.
A chest radiograph with normal findings in a 64-year-old woman who presented with worsening breathlessness.
A posteroanterior chest radiograph showing a peripheral wedge-shaped infiltrate caused by pulmonary infarction secondary to pulmonary embolism. Hampton hump is a rare and nonspecific finding. Courtesy of Justin Wong, MD.
- Computed tomography
- CT angiography (CTA) is the initial imaging modality of choice for stable patients with suspected pulmonary embolism. The ACR considers chest CTA the current standard of care for the detection of pulmonary embolism.28
- In patients with a negative CTA, the likelihood for subsequent thromboembolic events is extremely small.
- The Christopher study, a prospective trial, used CT as part of a management algorithm for 3306 outpatients with suspected acute pulmonary embolism. Patients in whom the Wells rule indicated that pulmonary embolism was unlikely underwent D-dimer testing; if the result was normal, pulmonary embolism was considered excluded. All other patients underwent multidetector CT arteriography, and pulmonary embolism was considered present or excluded based on the results. Among patients with negative scan results who did not receive anticoagulation therapy, the 3-month incidence of venous thromboembolism was 1.3%; death, possibly from pulmonary embolism, occurred in 0.5%.29
- Similarly, a meta-analysis published in 2004 reviewed 23 studies reporting on 4657 patients with negative pulmonary CTA results for pulmonary embolism who did not receive anticoagulation. The rate of venous thromboembolism was 1.4% and the rate of fatal pulmonary embolism was 0.51% at 3 months. These results are similar to negative results on conventional pulmonary angiography. These investigators concluded that withholding anticoagulation after negative pulmonary CTA results appears to be safe.30
- Spiral CT can visualize main, lobar, and segmental pulmonary emboli with a reported sensitivity of greater than 90%. Spiral CT scanning can help detect emboli as small as 2 mm that are affecting up to the seventh border division of the pulmonary artery. A further benefit of spiral CT scanning is that the results may suggest an alternative diagnosis in up to 57% of patients. A significant limitation of spiral CT scanning is that small subsegmental emboli may not be detected.
- The technique is as follows:
- Spiral CT examination is performed immediately after infusion of 150-200 mL of 30% contrast material.
- Scanning is performed from the level of the aortic arch to approximately 2 cm below the level of the inferior pulmonary vein while the patient is holding his or her breath at full inspiration.
- If the patient is not able to hold his or her breath for 20-30 seconds, scanning may be performed during gentle breathing.
- Sensitivity and specificity of spiral CT scanning for pulmonary embolism are as follows:
- The reported sensitivity is 53-100%.
- The reported specificity is 78-96%.
- The negative predictive value is 81-100%, and the positive predictive value is 60-100% for detecting emboli in segmental or larger arteries.
- Positive findings on CT imaging include a central intravascular filling defect within the vessel lumen, eccentric tracking of contrast material around a filling defect, and complete vascular occlusion. Smooth filling defects making an obtuse angle with a vessel wall may represent chronic thrombi or recent recanalization. In the lung parenchyma, signs of pulmonary embolism include oligemia, pulmonary hemorrhage (ground-glass attenuation), and pulmonary infarction (peripheral wedge-shaped pleural-based opacification).
- Pitfalls include the following:
- Technically inadequate scans may result from patients' dyspnea and/or obliquely or horizontally oriented vessels within the right middle lobe and left lingula.
- False filling defects may result from breathing artifact cardiac motion or unilateral extensive air space consolidation as a result of the significant decrease in blood flow through pulmonary arteries in these areas.
- Also see Acute Pulmonary Embolism (Helical CT).
- Combined spiral CT scanning for detection of pulmonary embolism and deep venous thrombosis (DVT)
- A combined CT scan for PE/DVT enhances the utility of spiral CT scanning by further identifying emboli in the deep venous system of the lower extremities or the pelvic veins.
- Good venous enhancement of the lower extremity veins occurs 2 minutes following lung CT scanning as 5-mm scans are performed at 5-cm intervals from the upper calves to the diaphragm.
- Alternatively, 1-cm images are performed from the iliac bones to the tibial plateau. The additional radiation dose needs to be considered in the formulation of this protocol. With this technique, up to 4% of patients with negative results on CT scanning examination for pulmonary embolism have been identified to have DVT.
A spiral CT scan shows thrombus in bilateral main pulmonary arteries.
A spiral CT scan shows thrombus in bilateral main pulmonary arteries.
CT scan of the same chest depicted in Image 18. Courtesy of Justin Wong, MD.
- Ventilation-perfusion (V/Q) scanning of the lungs: This is an important diagnostic modality for establishing the diagnosis of pulmonary embolism. However, V/Q scanning should be used only when CT scanning is not available or if the patient has a contraindication to CT scanning or intravenous contrast material.
- New criteria for V/Q scanning diagnosis of pulmonary embolism, from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II trial:
- High probability criteria are as follows:
- Two large (>75% of a segment) segmental perfusion defects without corresponding ventilation or chest radiographic abnormalities
- One large segmental perfusion defect and 2 moderate (25-75% of a segment) segmental perfusion defects without corresponding ventilation or radiographic abnormalities
- Four moderate segmental perfusion defects without corresponding ventilation or chest radiographic abnormalities
- Intermediate probability criteria are as follows:
- One moderate to fewer than 2 large segmental perfusion defects without corresponding ventilation or chest radiographic abnormalities
- Corresponding V/Q defects and radiographic parenchymal opacity in lower lung zone
- Single moderate matched V/Q defects with normal chest radiographic findings
- Corresponding V/Q and chest radiography small pleural effusion
- Difficult to categorize as normal, low, or high probability
- Low probability criteria are as follows:
- Multiple matched V/Q defects, regardless of size, with normal chest radiographic findings
- Corresponding V/Q defects and radiographic parenchymal opacity in upper or middle lung zone
- Corresponding V/Q defects and large pleural effusion
- Any perfusion defects with substantially larger radiographic abnormality
- Defects surrounded by normally perfused lung (stripe sign)
- More than 3 small (<25% of a segment) segmental perfusion defects with normal chest radiographic findings
- Nonsegmental perfusion defects (cardiomegaly, aortic impression, enlarged hila)
- Very low criterion is 3 small (<25% of a segment) segmental perfusion defects with normal chest radiograph findings.
- Normal finding is no perfusion defects and perfusion outlines the shape of the lung seen on a chest radiograph.
- In the PIOPED II study, very low-probability V/Q scans in patients whose Wells score indicated low pretest probability of pulmonary embolism reliably excluded pulmonary embolism.31
- High probability criteria are as follows:
High-probability perfusion lung scan shows segmental perfusion defects in the right upper lobe and subsegmental perfusion defects in right lower lobe, left upper lobe, and left lower lobe.
A normal ventilation scan will make the above-noted defects in Image 5 a mismatch and, hence, a high-probability ventilation-perfusion scan.
Anterior views of perfusion and ventilation scans are shown here. A perfusion defect is present in the left lower lobe, but perfusion to this lobe is intact, making this a high-probability scan.
A segmental ventilation perfusion mismatch evident in a left anterior oblique projection.
- Noninvasive tests for lower extremity DVT
- These may be helpful in the evaluation of patients who have nondiagnostic V/Q scan patterns of intermediate and low probability.
- Color-flow Doppler imaging and compression ultrasonography have a high sensitivity (89-100%) and specificity (89-100%) for detection of proximal DVT in symptomatic patients. However, compression ultrasonography has a low sensitivity (38%) and a low positive predictive value (26%) in patients without symptoms of DVT. Patients with positive findings for DVT can be anticoagulated irrespective of their V/Q scan results; other patients must have more invasive investigations performed to definitively rule out pulmonary embolism.
- Pulmonary angiography
- Pulmonary angiography remains the criterion standard for the diagnosis of pulmonary embolism.
- Following injection of iodinated contrast, anteroposterior, lateral, and oblique studies are performed on each lung.
- Positive results consist of a filling defect or sharp cutoff of the affected artery. Nonocclusive emboli are described to have a tram-track appearance.
- Abnormal findings on V/Q scans performed prior to angiography guide the operator to focus on abnormal areas.
- Angiography generally is a safe procedure. The mortality rate for patients undergoing this procedure is less than 0.5%, and the morbidity rate is less than 5%.
- Patients who have long-standing pulmonary arterial hypertension and right ventricular failure are considered high-risk patients.
- Negative pulmonary angiogram findings, even if false negative, exclude clinically relevant pulmonary embolism.
A pulmonary angiogram shows the abrupt termination of the ascending branch of the right upper-lobe artery, confirming the diagnosis of pulmonary embolism.
- Magnetic resonance imaging
- With MRI, evidence of pulmonary emboli may be detected by using standard or gated spin-echo techniques.
- Pulmonary emboli demonstrate increased signal intensity within the pulmonary artery. By obtaining a sequence of images, this signal that is originating from slow blood flow may be distinguished from pulmonary embolism. However, this remains a problem in pulmonary hypertension.
- Magnetic resonance angiography is performed following intravenous administration of gadolinium. Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or magnetic resonance angiography scans.
- NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.
- MRI has a sensitivity of 85% and specificity of 96% for central, lobar, and segmental emboli; MRI is inadequate for the diagnosis of subsegmental emboli.
- Echocardiography
- This modality generally has limited accuracy in the diagnosis of pulmonary embolism.
- Transesophageal echocardiography may identify central pulmonary embolism, and the sensitivity for central pulmonary embolism is reported to be 82%.
- Overall sensitivity and specificity for central and peripheral pulmonary embolism is 59% and 77%.
- Echocardiography may demonstrate right ventricular dysfunction in acute pulmonary embolism, predicting a higher mortality and possible benefit from thrombolytic therapy. Vanni et al reported that a right ventricular strain pattern is associated with a worse short-term outcome.32
Other Tests
- Electrocardiography
- The most common ECG abnormalities of pulmonary embolism are tachycardia and nonspecific ST-T wave abnormalities. These findings are not sensitive or specific enough to aid in the diagnosis of pulmonary embolism.
- The classic finding of right-sided heart strain demonstrated by an S1-Q3-T3 pattern is observed in only 20% of patients with proven pulmonary embolism.
More on Pulmonary Embolism |
| Overview: Pulmonary Embolism |
 Differential Diagnoses & Workup: Pulmonary Embolism |
| Treatment & Medication: Pulmonary Embolism |
| Follow-up: Pulmonary Embolism |
| Multimedia: Pulmonary Embolism |
| References |
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Further Reading
Keywords
pulmonary embolism, pulmonary emboli, venous thromboembolism, PE, obstructive shock, deep vein thrombosis, deep venous thrombosis, DVT, hemodynamic collapse, acute pulmonary infarction, pulmonary hypertension, cor pulmonale
pleuritic chest pain, hemoptysis, venous stasis, polycythemia, immobility, hypercoagulability, factor V Leiden mutation, pancreatic carcinoma, bronchogenic carcinoma, carcinoma of the genitourinary tract, colon cancer, breast cancer, congestive heart failure, stroke, obesity, varicose veins, inflammatory bowel disease
