Tests
1st tests to order
Pulmonary Embolism Rule-Out Criteria (PERC)
Test
Guidelines from the American College of Physicians recommend the application of the PERC to exclude pulmonary embolism (PE) in patients where initial clinical assessment suggests a low clinical suspicion of of PE.[127] One meta-analysis of studies that assessed the accuracy of PERC to rule out PE reported a sensitivity of 97%.[131]
In patients who meet all PERC criteria (age <50 years; initial heart rate <100 bpm; initial oxygen saturation >94% on room air; no unilateral leg swelling; no hemoptysis; no surgery or trauma within the last 4 weeks; no history of venous thromboembolism (VTE); no estrogen use), the risk for PE is considered to be lower than the risk of testing, and no further testing is indicated.[3][127]
Hemodynamically stable patients who do not meet all the PERC criteria, or with high clinical suspicion of PE, require further assessment using the original Wells criteria (modified), simplified Wells criteria (modified), original Geneva score (revised), the simplified Geneva score (revised), or the YEARS criteria.[3][128][129][130]
Result
fail to meet all criteria (positive score)
Wells criteria/Geneva score/YEARS criteria
Test
Hemodynamically stable patients who do not meet all the PERC criteria, or patients with high clinical suspicion of pulmonary embolism (PE) on initial evaluation, require assessment using the original Wells criteria (modified), simplified Wells criteria (modified), original Geneva score (revised), the simplified Geneva score (revised), or the YEARS criteria.[3][128][129][130]
Each of these clinical decision tools assigns a value (a single point, or points) to a series of historic and physical examination features, the sum of which determines whether PE is likely or unlikely. The YEARS criteria use a subset of the Wells criteria to create two levels of pretest probability, and use an adjusted D-dimer threshold to identify patients for whom PE can be safely ruled out without imaging.[130]
If these scoring systems suggest PE is unlikely, D-dimer measurement is recommended to assess the need for imaging.[3][127] See Criteria. Patients where Wells/Geneva or YEARS criteria suggest that PE is likely, or with an abnormal D-dimer, should proceed immediately to computed tomographic pulmonary angiography (CTPA; or ventilation-perfusion [V/Q] lung scan if CTPA is contraindicated), as should any patient with suspected PE with shock or hypotension.[127] In these patients, anticoagulation should be initiated while awaiting imaging results.[19][20] [ Pulmonary Embolism Wells Score Opens in new window ] [ Revised Geneva Score for Estimation of the Clinical Probability of Pulmonary Embolism in Adults Opens in new window ] [ YEARS Algorithm for Pulmonary Embolism (PE) Opens in new window ]
When each clinical decision tool (original Wells, modified Wells, simplified Wells, revised Geneva, and simplified revised Geneva; all with D-dimer testing if PE unlikely) was validated in a primary care dataset, sensitivity ranged from 88% (simplified revised Geneva) to 96% (simplified Wells) and specificity from 48% (revised Geneva) to 53% (simplified revised Geneva).[132]
The simplified versions of the modified Wells criteria or revised Geneva score may be preferred in clinical practice because of their ease of use.[133] Both simplified versions have been validated; neither has been shown to be superior to the other.[3][132] However, the Geneva score is based entirely on objective clinical items and may be more reproducible (the Wells criteria [original and simplified] include the subjective clinical item "alternative diagnosis less likely than PE").[134] The YEARS criteria adjusts D-dimer threshold to exclude PE based on number of criteria present. It avoids imaging in the highest percentage of patients, but maintains the subjective elements from the Wells criteria.[130]
The Wells criteria and revised Geneva score categorize patients dichotomously (PE unlikely or PE likely). However, earlier iterations of each tool attributed low, intermediate, or high clinical probabilities of PE. If the two-level classification is used, PE is confirmed in 50% of patients in the PE-likely category compared with 12% in the PE-unlikely category. If the three-level classification is employed, the proportion of patients with confirmed PE will be around 10% in the low probability category, 30% in the intermediate probability category, and 65% in the high probability category.[135]
Clinical (pretest) probability score alone is not enough to diagnose or exclude PE. It must be combined with additional tests.
Result
original Wells criteria: PE unlikely ≤4, PE likely >4; simplified Wells criteria: PE unlikely ≤1, PE likely >1; revised Geneva score: PE unlikely ≤5, PE likely >5; simplified Geneva score: PE unlikely ≤2, PE likely >2; YEARS criteria: D-dimer <1000 ng/mL rules out PE if 0 criteria met; D-dimer <500 ng/mL rules out PE if ≥1 criteria met.
D-dimer test
Test
D-dimer testing is indicated in hemodynamically stable patients who did dot meet all the criteria of PERC and where pulmonary embolism (PE) has been assessed as unlikely using a validated clinical decision tool (original Wells, modified Wells, simplified Wells, revised Geneva, simplified revised Geneva, or YEARS criteria).[3][127]
Clinicians should not obtain a D-dimer measurement in patients with a high clinical suspicion of PE; immediate imaging is indicated.[127]
D-dimer testing is highly sensitive (>95%) but nonspecific.
A plasma D-dimer level below threshold safely excludes PE in patients with an unlikely (intermediate or low) pretest probability of PE, and no further testing is required.[3][124]
The risk of PE within 3 months is <1% in these patients.[142][143]
D-dimer may be adjusted to age (normal is <age x 10 micrograms/L in patients 50 years or older) or pretest probability of disease (1000 nanograms/mL cutoff in low-probability patients, or 500 nanograms/mL in intermediate probability patients) to increase the specificity, and thus the percentage of patients who can avoid an imaging study.[3][144][145]
When using the YEARS criteria, D-dimer threshold is adjusted according to the number of criteria present.[130][145]
In patients with cancer, using an age-adjusted D-dimer cutoff doubled the proportion of patients in whom PE could be excluded by clinical decision rule and D-dimer, without imaging.[146] The YEARS algorithm with risk-adapted D-dimer thresholds has also been studied in pregnant patients suspected of PE.[136]
Patients with an abnormal D-dimer level should undergo multiple-detector CTPA (or V/Q lung scan if CTPA is contraindicated) to confirm or exclude a diagnosis of PE.[3][124][127]
Result
elevated
multiple-detector computed tomographic pulmonary angiography (CTPA)
Test
Ordered for patients where pulmonary embolism (PE) is assessed as likely based on a validated prediction tool (original Wells criteria [modified], simplified Wells criteria [modified], original Geneva score [revised], the simplified Geneva score [revised], or the YEARS criteria) or D-dimer above threshold.[3][127][137][138][139]
CTPA has the best diagnostic accuracy of all advanced noninvasive imaging methods; CTPA confirms the diagnosis by direct visualization of thrombus in a pulmonary artery, where it appears as a partial or complete intraluminal filling defect.[147] The likelihood ratio to rule in a PE with a filling defect in the segmental or subsegmental branches is 24.1 (range of 12.4 to 46.7), whereas the likelihood to rule it out is 0.11 (range of 0.06 to 0.19).[147]
Specificity is 96%.[148] Three-month incidence of a subsequent venous thromboembolic event following a negative CT scan is <2%.[147][149]
CT scans are contraindicated in approximately 25% of patients due to contrast allergy or renal failure.[148] In pregnant women, radiation exposure through CT scan is at a dose much lower than the exposure associated with fetal harm and, if necessary, CTPA not be withheld from pregnant patients.[150]
CTPA should be used with discretion in adolescents and young adults, and alternative imaging strategies employed where possible.[151][152] If it is used, ionizing radiation exposure should be carefully monitored and minimized.[153]
[Figure caption and citation for the preceding image starts]: Contrasted CTPA scan showing subsegmental right pulmonary artery emboli (see arrows)From the collection of Seth W. Clemens; used with permission [Citation ends].
Result
diagnosis is confirmed by direct visualization of thrombus in a pulmonary artery; appears as a partial or complete intraluminal filling defect
ventilation-perfusion (V/Q) scan
Test
V/Q lung scan, preferably using single photon emission computed tomography (SPECT; which may reduce the number of inconclusive scans), is an alternative to CTPA.[154]
A prospective study of patients with suspected acute pulmonary embolism (PE) reported a sensitivity of 97% and a specificity of 88% for V/Q SPECT scan.[155] In a retrospective study of 2328 patients with clinically suspected PE, 601 of 608 patients with a final diagnosis of PE had a positive V/Q SPECT scan (99% sensitivity), and 1153 patients without final PE diagnosis had a negative V/Q SPECT scan (98% specificity).[156] A negative V/Q scan effectively excludes PE.
V/Q scan is a radiation- and medium-sparing procedure and may be appropriate for patients with contraindications or relative contraindications to CT (e.g., contrast allergy, moderate to severe renal failure, pregnancy, young patients).[3] Consider a V/Q lung scan rather than CTPA to diagnose PE in young women with a normal chest radiograph to reduce the overall radiation dose to the breast.[3][157] Methods include planar V/Q, SPECT and SPECT with concomitant low-dose computed tomography (Q-SPECT-CT). SPECT based methods have fewer indeterminate results.[158]
Result
PE likely when an area of ventilation is not perfused; a negative V/Q scan effectively excludes PE
coagulation studies
Test
International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) should be ordered.
Required to establish baseline prior to commencing anticoagulation. Prolonged values, especially aPTT, in the absence of exposure to an anticoagulant, may suggest antiphospholipid antibody syndrome.
Aids decisions about the safety and type of initial anticoagulation to prescribe.
Result
baseline values; establishing correct therapeutic range
BUN and creatinine, hepatic function tests
Test
The choice of anticoagulant and doses of some anticoagulants may need to be adjusted in patients with renal or hepatic impairment. Baseline values should be obtained.
Result
baseline values; decision on most appropriate anticoagulant and dose
CBC
Test
May detect hematologic abnormalities.
Heparin therapy can be associated with heparin-induced thrombocytopenia; platelet count should be measured at baseline and regularly throughout heparin treatment.
Elevated platelet count may suggest essential thrombocytosis or a myeloproliferative disorder, which may represent a secondary hypercoagulable state.
May detect anemia, leukopenia.
Result
baseline values
Tests to consider
Point-of-care ultrasound (POCUS)
Test
POCUS is a rapid imaging study performed at the bedside by the physician or other trained clinician. Guidelines support its use to evaluate potential etiologies for acute dyspnea, but the precise fit into the diagnostic algorithm for patients clinically suspected of pulmonary embolism requires further exploration.[159]
Result
evidence of thrombus in heart, lung, inferior vena cava or deep veins; may reveal alternate diagnosis
chest x-ray
Test
A normal chest x-ray does not confirm or eliminate pulmonary embolism (PE) as a diagnosis[139] However, a chest-ray may rule out other causes of a patient’s symptoms such as pneumothorax or pneumonia.[139]
May show Fleischner sign/prominent central pulmonary artery (20%); Westermark sign/oligemia in PE area of distribution (11%); Hampton hump/pleural-based areas of increased opacity corresponding to the distribution of the PE (27%).[129][160] None of these findings are neither sufficiently sensitive nor specific to allow a definitive diagnosis.
Result
band atelectasis, elevation of hemidiaphragm, prominent central pulmonary artery, oligemia at site of embolism
magnetic resonance angiography (MRA)
Test
MRA can be used to evaluate the central and segmental arteries, though MR based imaging is rarely used due to the ease and performance characteristics of CTPA.[139]
Three different techniques are available: gadolinium-contrast enhanced angiography (Gd-MRA), real-time angiography (RT-MRA), and MR-perfusion images.[161][Figure caption and citation for the preceding image starts]: Gd-MRA showing a right main pulmonary artery pulmonary embolism (see arrow)From the collection of Seth W. Clemens; used with permission [Citation ends].
Can be used to evaluate the central and segmental arteries.[139]
High specificity (91% to 98%) allows for accurate diagnosis.
Low sensitivity (75% to 93%) cannot reliably exclude pulmonary embolism with a negative test.[161]
Gadolinium contrast, used in Gd-MRA and MR perfusion studies, is relatively contraindicated in pregnancy.
Due to cost, longer acquisition time and operating characteristics, MR modalities are used infrequently.
Result
diagnosis is confirmed by direct visualization of thrombus in a pulmonary artery; appears as a partial or complete intraluminal filling defect
pulmonary angiography
Test
Despite its diagnostic accuracy, invasive pulmonary angiography is rarely used for the diagnosis or exclusion of pulmonary embolism.[3][162] It is associated with risk of morbidity/mortality, and (less invasive) CTPA affords comparable diagnostic precision.[3][163]
Negative predictive value may be as high as 99%.[164]
Invasive test with morbidity of 3% to 6% and a mortality of 0.2% to 0.5%.[163][165]
Involves the use of contrast; a relative contraindication in pregnancy and renal failure.
Result
diagnosis made by visualization of a complete or incomplete filling defect in the pulmonary artery
transthoracic echocardiography (TTE)
Test
TTE is generally not indicated in the diagnosis of acute pulmonary embolism (PE), but it is useful in identifying right ventricular strain and assisting with severity classification and determining prognosis.[3][139] Echocardiographic evidence of right heart thrombi is significantly associated with increased 30-day mortality in patients diagnosed with acute PE.[166][Figure caption and citation for the preceding image starts]: Gd-MRA showing a right main pulmonary artery pulmonary embolism (see arrow)From the collection of Seth W. Clemens; used with permission [Citation ends]. If a definitive imaging modality is unavailable, echocardiography may be considered for patients with suspected PE presenting with shock or hypotension.[3][124]
Result
right heart strain, right heart thrombi
electrocardiography (ECG)
Test
ECG cannot definitively establish or eliminate PE as a diagnosis, and specific findings may only be suggestive of pulmonary embolism (PE).[118][174][175]
ECG can, however, be used to assess right ventricular function in patients with confirmed PE without shock or hypotension.[3][19] Right ventricular dysfunction is predictive of adverse outcome and enables risk stratification in these patients.[176][177][178]
Result
right ventricular dysfunction; right ventricular enlargement
arterial blood gasses (ABG)
Test
ABG analysis is of very limited diagnostic utility, alone or in combination with other clinical variables, in suspected pulmonary embolism (PE).[179] Hypoxemia is considered to be a typical finding in acute PE, but ABG analysis is of very limited diagnostic utility, alone or in combination with other clinical variables, in suspected PE.[3][179]
A PaO₂ <80 mmHg, a PaCO₂ <36 mmHg, or an abnormal alveolar-arterial gradient (A-aO₂) are not predictive of PE in patients suspected of having PE.[179]
Result
hypoxia and hypocapnia may be suggestive
thrombophilia screen
Test
Indications for screening are controversial.[169][170] Hereditary thrombophilia does not sufficiently modify the predicted risk of recurrent thrombosis to affect treatment decisions, and a conservative approach to testing is reasonable.[19] Some guidelines suggest testing only in situations where the result is likely to change a clinical decision (such as in patients with unprovoked deep vein thrombosis or pulmonary embolism who are considering stopping anticoagulants).[20][61][171] However, the presence of a hereditary thrombophilia does not significantly increase the predicted risk of recurrent VTE after a provoked VTE, and guidelines discourage testing in this setting.[3][60] Antiphospholipid antibodies may predict a higher risk of future thrombosis following an initial VTE event and may impact selection of therapy.[65] It is controversial whether broad screening for antiphospholipid antibodies, or screening only on the basis of clinical suspicion, is preferred.[172][173] Testing should be performed when results are likely to impact management, and at a time when results are not confounded by acute thrombosis or therapeutics.[169]
If a hereditary thrombophilia screen is considered, it should be deferred until a minimum of 3 months of anticoagulant therapy has been completed because some thrombophilia tests are influenced by the presence of acute thrombosis or anticoagulant therapy.[169] For antiphospholipid antibody screening, cardiolipin and beta-2 glycoprotein-I antibodies can be performed without regard to the presence of anticoagulants; however, most anticoagulants interfere with assays for lupus anticoagulant.[65]
Result
positive in inherited thrombophilias; elevated titers/abnormal result in antiphospholipid syndrome
ultrasonography
Test
Bilateral venous compression ultrasound to establish the presence of thrombosis suggestive of pulmonary embolism (PE) is recommended in pregnant patients with suspected PE with leg symptoms.[3][167] Diagnosis of DVT may be sufficient basis to initiate therapy and allow avoidance of chest imaging.[188] However, normal ultrasound does not exclude PE.
Result
inability to fully compress lumen of vein using ultrasound transducer
troponin
Test
Troponin can be used to assist in determining the severity category of acute pulmonary embolism, which impacts management decisions.
It is suggested in patients who have either an elevated Pulmonary Embolism Severity Index (PESI) category, or abnormalities of the right ventricle on imaging.[3]
Result
may be elevated; may be useful for prognosis
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