Investigations
1st investigations to order
computed tomographic pulmonary angiography (CTPA)
Test
CTPA is the preferred investigation for definitive confirmation of PE. It is indicated in:
Patients with suspected PE who are haemodynamically unstable at presentation (provided CTPA is immediately available and the patient is well enough to have it - in practice this is often not the case and echocardiography is used instead)
Patients who are classified as ‘PE likely’ based on Wells (or Geneva) score
Patients who are classified as ‘PE unlikely’ based on Wells or Geneva score but who have a positive D-dimer test[76]
Patients with a positive D-dimer test when combined with the YEARS criteria[67]
Pregnant patients, especially those who have an abnormal initial CXR.[67]
Avoid CTPA if possible in younger patients, especially if PE can be ruled out by other non-invasive methods with less radiation exposure.[94]
PE does not need to be confirmed on CTPA prior to discharge in low-risk patients (Pulmonary Embolism Severity Index score [PESI] I-II or sPESI 0) who are suitable for outpatient management but it should be performed within 24 hours (if available).[106]
Evidence: CTPA risks
CTPA must be used judiciously to ensure benefits outweigh risks.
Radiation from CT is considered to be a risk factor for certain cancers.
In one study, a cohort of children with CT exposure was found to have a significantly higher incidence of leukaemia and brain tumours later in life.[74]
However, CT technology has evolved, and several techniques can now reduce radiation exposure without compromising image quality, particularly in pregnant women.[113][114]
Both maternal and fetal radiation exposure are low using modern imaging techniques; fetal radiation doses are well below the threshold associated with fetal radiation complications and the effect on maternal cancer risk is negligible (lifetime cancer risk is reportedly increased by a factor of 1.0003 to 1.0007).[113][114][115][116][117][118][119][120]
Therefore, do not avoid CTPA on the grounds of maternal cancer risk.[67]
The contrast dye used in CTPA for the evaluation of PE may cause nephropathy.
In a prospective study, 174 patients underwent CTPA, which demonstrated acute PE in 7%. Some 12% developed contrast-induced nephropathy including one patient with acute PE. Development of contrast-induced nephropathy was associated with an increased risk of severe abnormal kidney function or established kidney failure and death within the subsequent 45 days.[121]
Repeated imaging is common, which may magnify these risks.
In one study performed at a large academic centre, at least one third of emergency department patients who had CTPA for the evaluation of PE underwent another CT for the same reason within 5 years.[122]
More widespread use of CTPA may lead to overdiagnosis of subsegmental PEs that are often of little clinical significance.
The diagnostic value and clinical significance of subsegmental defects identified on CTPA remains hotly debated.[67][123]
Evidence suggests that there has been minimal or no associated change in patient outcomes despite the increased use of CTPA. It is thought that this is due to increased identification of less severe PEs (such as subsegmental PEs) that would not have previously been diagnosed and that may not be clinically relevant.[123][124][125][126]
There is a lack of evidence to support decisions on whether or not to treat patients who have incidental PE detected by CTPA, although they probably should be treated if they have cancer and a proximal clot.[67][123][127]
Potentially inappropriate overuse of CTPA results in increased risks to patients as well as higher costs.[74]
Evidence: CTPA predictive value
The predictive value of CTPA depends on the pre-test probability of PE.
The PIOPED II trial highlighted the influence of clinical probability on the predictive value of CTPA.[128]
The negative predictive value for PE of a negative CTPA was dependent on pre-test clinical probability of PE as assessed by the Wells Score (96% for those with a low probability pre-test Wells Score and 89% for those with an intermediate probability score but only 60% for those with a high probability Wells score - based on the three-level Wells Score).
Conversely the positive predictive value of a positive CTPA was high (92% to 96%) in patients with an intermediate or high probability pre-test Wells Score but only 58% in those with a low probability pre-test score.
Therefore, clinicians should be particularly cautious in case of discrepancy between clinical judgement and the CTPA result. However a normal CTPA excludes a PE in a patient whose pre-test Wells (or Geneva) score categorised them as PE unlikely.[67]
echocardiography
Test
Use bedside echocardiography for haemodynamically unstable patients who cannot have CTPA.
If CTPA is not immediately available or the patient is too unwell to be moved, perform a bedside echocardiography.
The presence of any signs of right ventricular (RV) dysfunction is sufficiently suggestive of PE to confirm the diagnosis and justify urgent reperfusion treatment (usually thrombolysis).[67][77]
Do not use echocardiography routinely in haemodynamically stable patients with suspected PE.
However, if it has been performed as part of the diagnostic work-up and shows evidence of RV dysfunction, consider further risk stratification by measuring a cardiac biomarker.[106]
Echocardiography can also identify important alternative causes of shock, such as pericardial tamponade, acute valvular dysfunction, severe global or regional left ventricular dysfunction, aortic dissection, or hypovolaemia.
Practical tip
A negative echocardiography does not exclude PE.[67]
The reported negative predictive value for PE is 40% to 50%.
Assessment of RV function on echocardiography is not obligatory for the identification of low-risk patients who are suitable for outpatient management.[106]
However, if it has been performed as part of the diagnostic work-up for PE and shows evidence of RV dysfunction, consider measuring a cardiac biomarker to further risk stratify the patient.
Result
abnormal RV ejection pattern (so-called ‘60-60 sign’)[67]
reduced contractility of the RV free wall compared with the RV apex ( ‘McConnell sign ’)[67]
RV dilatation and hypokinesis
RV diameter/LV diameter >0.9
interventricular septal flattening and paradoxical leftward septal motion
presence of tricuspid regurgitation
presence of pulmonary hypertension (peak tricuspid jet velocity greater than 2.6 m/s and loss of respirophasic inferior vena cava collapse)
mobile right heart thrombi can be detected by transthoracic or transoesophageal echocardiography (or by CT angiography) in less than 4% of unselected patients with PE
This finding essentially confirms the diagnosis of PE.
This finding is associated with RV dysfunction and high early mortality.[67]
D-dimer
Test
Non-pregnant patients
Use a clinical probability score to determine whether a patient needs D-dimer testing.
Request D-dimer testing in any haemodynamically stable patient whose Wells (or Geneva) score categorises them as ‘ PE unlikely’. An alternative approach is to use D-dimer adjusted to age for patients aged over 50 years.[67][74][76] Follow local protocols.
Offer anticoagulation (unless contraindicated) if the D-dimer result cannot be obtained within 4 hours.
Do not use D-dimer testing in patients whose Wells (or Geneva) score categorises them as ‘PE likely’ as a negative result will not remove the need for further imaging.[74]
A normal plasma D-dimer level safely excludes PE in patients with an unlikely pre-test probability of PE and no further investigation is required.[67][74][76] The risk of PE within 3 months is <1% in these patients.[101]
If a patient has a raised D-dimer level, start anticoagulation (unless contraindicated) and arrange CTPA to confirm or exclude PE (unless a concurrent deep vein thrombosis [DVT] is suspected).[67][74][76]
D-dimer testing is highly sensitive (>95%) in patients in whom pre-test probability suggests that PE is unlikely.[74] However, its specificity is low and may decline with increasing patient age.[74] Use of an age-adjusted D-dimer level may improve the performance of D-dimer testing in patients aged over 50 years.[67][76]
Pregnant patients
Request D-dimer testing in all pregnant patients with suspected PE.[79][80]
Use the D-dimer result in combination with the YEARS criteria to assess the clinical probability of PE. The YEARS criteria are: [67][79][80]
Clinical signs of DVT
Haemoptysis
PE is the most likely diagnosis.
PE can be safely ruled out if:[79][80]
None of the YEARS criteria are met and the D-dimer level is <1000 ng/mL
≥1 of the YEARS criteria are met and the D-dimer level is <500 ng/mL.
Start anticoagulation (unless contraindicated) and arrange definitive imaging to confirm or exclude PE (unless a concurrent DVT is suspected) if:[79][80]
None of the YEARS criteria are met and the D-dimer level is ≥1000 ng/mL
≥1 of the YEARS criteria are met and the D-dimer level is ≥500 ng/mL.
Practical tip
Order a lower limb compression venous ultrasound if a concurrent DVT is suspected as this may avoid using CTPA.[79]
Practical tip
Remember that a D-dimer level is a continuous variable.
A low D-dimer does not mean no risk of PE and a slightly higher D-dimer does not mean a step increase in PE risk.
The threshold value (check what value is used by your local laboratory) is the optimum for balancing sensitivity and specificity.
In practice, many people have a raised D-dimer without having a PE.
Result
elevated (typically >500 ng/mL[76] but check the threshold used by your local laboratory)
full blood count
Test
May indicate thrombocytopenia or anaemia. These patients are at an increased risk of complications from bleeding when taking an anticoagulant.
Heparin therapy can be associated with heparin-induced thrombocytopenia; measure platelet count at baseline and regularly throughout treatment.
May also indicate thrombocythaemia or polycythaemia which increase the risk of venous thromboembolism.
Result
baseline values
ECG
Test
An ECG is not diagnostic of PE but can be useful to support the diagnosis of PE or rule out other causes.
Evidence: ECG
Some ECG signs are predictors of a poor outcome.
A systematic review and meta-analysis looked at the value of using ECG in predicting clinical deterioration and mortality in acute PE.
It found that ECG signs that were good predictors of a poor outcome included S1Q3T3, complete right bundle branch block, T-wave inversion, right axis deviation, and atrial fibrillation.[111]
How to record an ECG. Demonstrates placement of chest and limb electrodes.
Result
normal sinus rhythm
sinus tachycardia
new right bundle branch block (complete or incomplete)
QR pattern in V1
S1Q3T3 pattern
T wave inversion in V1-V4
ST segment migration in V1 through V4
atrial arrhythmias, most frequently atrial fibrillation
non-specific ST-segment and T-wave abnormalities
right axis deviation
urea and electrolytes
Test
Check baseline kidney function. Doses of some anticoagulants (e.g., low molecular weight heparin, fondaparinux, apixaban, rivaroxaban, dabigatran, edoxaban) may need to be adjusted in patients with abnormal kidney function.[76]
Kidney function results can also be used to guide investigations. For example, using CTPA in patients with severe abnormal kidney function can risk contrast-induced nephropathy.
Result
baseline values
coagulation studies
Test
Order international normalised ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT). These are needed to establish baseline values before starting anticoagulation.
Also aids decisions about the safety and choice of initial anticoagulation.[76]
Result
baseline values
liver function tests
Test
Abnormal LFTs can influence the choice of anticoagulation.
Result
baseline values
Investigations to consider
arterial blood gas (ABG)
Test
Do not perform an ABG if the oxygen saturations are within normal range on room air.
Consider ABG in patients who have low oxygen saturations. However, be aware that it is of very limited diagnostic utility, either alone or in combination with other clinical variables, in suspected PE.[104]
Evidence: ABG
ABG has a limited role in diagnosing PE.
A PaO 2 <80 mmHg (10.7 kPa), a PaCO 2 <36 mmHg (4.6 kPa), or an abnormal alveolar-arterial gradient (A–aO 2) are not predictive of PE in patients suspected of having PE.[104] [ A-a Gradient Opens in new window ]
In patients with suspected acute PE with normal ABG results, PE could not be excluded in 38% of those without cardiopulmonary disease or in 14% who had pre-existing cardiopulmonary disease.[105]
How to obtain an arterial blood sample from the radial artery.
Result
hypoxaemia and hypocapnia may be suggestive of PE[76]
chest x-ray (CXR)
Test
Not diagnostic of PE but may be useful to support the diagnosis and is important to rule out other causes.
It is usually normal in a patient with a PE but an abnormal CXR does not rule out PE.[76]
Practical tip
Pulmonary infarction secondary to PE can be difficult to distinguish from pneumonia on CXR.
Result
usually normal but may show atelectasis; pleural effusion elevation of hemidiaphragm can be suggestive of a PE[76]
lower limb compression venous ultrasound
Test
Use lower limb compression venous ultrasound to investigate patients suspected of having a concurrent deep vein thrombosis (DVT).
Finding a proximal DVT in patients suspected of having PE is considered sufficient to start anticoagulant treatment without further investigation.[67]
Evidence: Ultrasound
Lower limb ultrasound has high sensitivity/specificity for DVT.
Lower limb compression venous ultrasound has a sensitivity >90% and a specificity of approximately 95% for symptomatic DVT and shows a DVT in 30% to 50% of patients with PE.[67]
Result
inability to fully compress lumen of vein using ultrasound transducer
cardiac biomarker
Test
The cardiac biomarkers high-sensitivity troponin (either I or T), N-terminal pro-B-type natriuretic peptide (NT-proBNP), or B-type natriuretic peptide (BNP) are not used in diagnosing PE but can aid prognostic assessment.[77][106]
They can be used in combination with risk stratification scoring (Pulmonary Embolism Severity Index score [PESI]/simplified PESI [sPESI]) to guide decisions about early discharge for low-risk patients.[67]
Measure a cardiac biomarker in a patient with a confirmed or highly suspected PE (positive D-dimer or Wells score >4) if:[106]
Risk stratification puts the patient in the intermediate-risk group (PESI III-IV or sPESI ≥1)[67]
OR
Risk stratification puts the patient in the low-risk group (PESI I-II or sPESI 0), AND all of the following criteria are met:
Incidental right ventricular (RV) dysfunction was identified on CTPA or echocardiography performed as part of the diagnostic work-up
AND
The patient is considered potentially suitable for outpatient management[106]
Do not use routinely to risk stratify patients.
Seek senior review if there is an incidental finding of an elevated troponin in a patient with a low-risk PE (PESI I or II/sPESI 0).
An alternative cause for elevated troponin should be considered.[106]
For more detail on risk stratification, see Management recommendations.
Evidence: Cardiac biomarkers
Elevated cardiac biomarkers predict a worse outcome.
Elevated plasma troponin levels on admission have been reported to be associated with a worse prognosis.
A meta-analysis covering a total of 1985 patients showed elevated cardiac troponin I or T concentrations in approximately 50% of the patients with acute PE. Elevated troponin concentrations were associated with higher mortality both in unselected patients and haemodynamically stable patients.[107]
Use of age-adjusted high-sensitivity troponin T cut-off values (≥14 picograms/mL for patients aged <75 years and ≥45 picograms/mL for those aged ≥75 years) may further improve the negative predictive value of this biomarker.[108]
Low levels of BNP or NT-proBNP can identify patients with a favourable short-term outcome based on their high negative predictive value.[109]
The plasma levels of BNP and NT-proBNP reflect the severity of haemodynamic compromise and (presumed) RV dysfunction in acute PE. Right ventricular pressure overload is associated with increased myocardial stretch, which leads to the release of BNP or NT-proBNP and therefore raised plasma levels.[67]
A meta-analysis found that 51% of 1132 unselected patients with acute PE had elevated BNP or NT-proBNP concentrations on admission. These patients had a 10% risk of early death and a 23% risk of an adverse outcome.[110]
ventilation-perfusion (V/Q) scan
Test
Use of V/Q scan will depend on local availability; check local protocols.[67]
A V/Q scan is being increasingly used as an alternative to CTPA, particularly for patients who have a contraindication to CTPA (such as abnormal kidney function or contrast allergy).[67][74][76][129]
V/Q may be preferred over CTPA in some patient groups to avoid unnecessary radiation, particularly in younger patients in whom CTPA may raise the lifetime risk of cancer.[67][74]
V/Q may be used in pregnant women who have a normal initial chest x-ray.[67]
A V/Q SPECT (single-photon emission computed tomography) scan is commonly used; a V/Q planar scan is an alternative if this is not available.[76]
Practical tip
A V/Q scan is of limited use in patients with significant underlying lung disease, left ventricular failure, or congestive cardiac failure.[67]
Evidence: Ruling out PE with a V/Q scan
For patients with suspected PE who are unable to have CTPA, guidelines recommend a V/Q SPECT (single-photon emission computed tomography) scan or V/Q planar scan as an alternative; however, the evidence is limited.
The UK National Institute for Health and Care Excellence (NICE) 2023 venous thromboembolic diseases guideline recommends a CTPA scan as first-line imaging in people with suspected PE and a Wells score >4.[76] For people with an allergy to contrast media, with severe abnormal kidney function, or at a high risk from irradiation, NICE recommends assessing the suitability of a V/Q SPECT or a V/Q planar scan (if V/Q SPECT is not available) as an alternative.
NICE identified one randomised controlled trial (n=1417) comparing V/Q scanning with CTPA in patients in whom VTE had initially been excluded.[76][130]
There was a possible clinically important decrease in mortality in patients who received a CTPA scan compared with V/Q scan (RR 0.62 [95% CI 0.34 to 1.11], absolute effect 19 fewer per 1000 [from 32 fewer to 5 more], moderate-quality evidence as assessed by GRADE).
However, there was no difference in symptomatic PE or proximal DVT events (RR 0.36 [95% CI 0.07 to 1.79], absolute effect 6 fewer per 1000 [from 9 fewer to 8 more], GRADE low).
Five diagnostic studies were identified for V/Q scans; one of these studies assessed the diagnostic accuracy of both V/Q planar lung scintigraphy and V/Q SPECT.[76]
Sensitivity and specificity for planar V/Q scans ranged from 41% to 100% and 72% to 97%, respectively. However, some studies had high numbers of non-diagnostic or indeterminate scans that were excluded from the study analysis, making planar V/Q seem more effective (GRADE very low).
One small study (n=41) calculated sensitivity and specificity of V/Q SPECT as 100% and 87%, respectively (GRADE very low). However, five indeterminate scans were not accounted for in the analysis so the accuracy may have been overestimated.[131]
The 2019 European Society of Cardiology (ESC) guideline also states that CTPA is the imaging of choice with V/Q planar scans or V/Q SPECT as an alternative.[67] The ESC notes that the evidence for V/Q SPECT is limited because:
Most studies are retrospective
Some studies include SPECT itself in the reference standard
Diagnostic criteria for PE vary between studies
The optimal scanning technique has not been validated.
Result
PE likely when an area of ventilation is not perfused[67]
further investigation for unprovoked PE
Test
An unprovoked PE is a PE in a patient who had no pre-existing, transient provoking risk factor in the prior 3 months.[76]
Provoking risk factors include: surgery; trauma; significant immobility (bedbound, unable to walk unaided or likely to spend a substantial proportion of the day in bed or in a chair); pregnancy or puerperium; use of oral contraceptive/hormone replacement therapy).
An unprovoked PE may be suggestive of an underlying condition so further investigations are sometimes warranted.
Undiagnosed cancer
In any patient diagnosed with unprovoked PE who is not known to have cancer:[76]
Review medical history
Review baseline blood tests including full blood count, kidney and hepatic function, prothrombin time (PT) and activated partial thromboplastin time (APTT)
Offer a physical examination.
Do not offer further investigations for cancer for patients with an unprovoked PE unless they have relevant clinical symptoms or signs.[76]
Evidence: Cancer screening
The evidence supporting screening for undiagnosed cancer after unprovoked venous thromboembolism is inconclusive.
A screening strategy that was proposed in the SOMIT trial included pelvic and abdominal CT combined with mammography and sputum cytology. This was recommended as the most effective and least harmful approach for patients.
However, no 5-year survival benefit was found when this approach was compared with basic clinical evaluation.[134][135]
Thrombophilia testing
Consider testing for hereditary thrombophilia in patients who don't have an identifiable risk factor and have a first degree relative who has had a VTE, if it is planned to stop anticoagulation.[76]
Do not routinely offer thrombophilia testing to first-degree relatives of people with a history of PE and thrombophilia.[76][136]
Consider testing for antiphospholipid antibodies in patients who have had an unprovoked PE if it is planned to stop anticoagulation treatment.[76]
Practical tip
Be aware that tests for hereditary thrombophilia and antiphospholipid antibodies can be affected by anticoagulation; specialist advice may be needed.[76]
Result
Emerging tests
biomarkers
Test
Evidence has shown that certain biomarkers may be of use when assessing prognosis in PE. These include heart-type fatty acid-binding protein (H-FABP), lactate, neutrophil gelatinase-associated lipocalin, cystatin C, creatinine, and vasopressin. However, they are not widely used in clinical practice.[67]
These biomarkers have been combined with clinical parameters to form prognostic scoring tools (e.g., the Bova score), although the implications for patient management remain unclear.[67]
Result
point-of-care D-dimer testing
Test
Point-of-care D-dimer testing may be increasingly used if laboratory facilities are not immediately available (e.g., in the community to avoid sending a patient to hospital and particularly in remote areas where access to health care is limited). However, point-of-care assays have a lower sensitivity and negative predictive value compared with laboratory-based D-dimer tests. Therefore, point-of-care D-dimer testing should only be used in patients with a low pre-test probability.[67][76]
Result
D-dimer adjusted to clinical probability
Test
D-dimer adjusted to clinical probability has also been shown to be effective in non-pregnant patients. In a prospective management trial that used the YEARS decision tool, CTPA was avoided in 48% of patients, compared with 34% if the Wells criteria and fixed D-dimer cut-off of 500 ng/mL was used.[139]
Result
magnetic resonance angiography (MRA)
Test
The hypothesis is that a that a negative MRA combined with the absence of proximal deep vein thrombosis on lower limb compression venous ultrasound may safely rule out clinically significant PE.[67]
Result
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