18th February 2025

Pulmonary embolism

Clinical features of PE

Pulmonary embolism (PE) is a condition where one or more dislodged thrombi occlude the pulmonary vasculature, which may cause severe respiratory dysfunction.

Clinical features of acute PE include dyspnoea, pleuritic chest pain, hypoxaemia, tachycardia, cough and haemoptysis. Dizziness, syncope, elevated JVP, gallop rhythm and tricuspid regurgitant murmur are suggestive of right ventricular strain and failure. There may be associated distal limb findings suggestive of a DVT. Hypotension and cardiac arrest are the most serious presentations of acute PE.

Risk factors for PE

Around 30-50% of VTEs are unprovoked, with no identifiable risk factor. However, important risk factors include (from the European Society of Cardiology):

Table 1 Risk factors for PE

Assessing the clinical probability of PE

Various clinical scoring systems are used to assist with objective assessment of the probability of PE and therefore the need (or not) to do further investigations:

• If PE is a differential but with low suspicion: pulmonary embolism rule-out criteria (PERC rule)
• If there is significant suspicion of PE (and/or PERC is positive): Wells’ criteria for PE

Table 2 PERC tool for PE

Table 3 Wells’ score for PE

Investigations in PE in a non-pregnant patient

Common investigations in suspected PE include:

• ECG: the most common finding is sinus tachycardia; other abnormalities include non-specific ST-segment and T-wave abnormalities, right axis deviation, right bundle branch block, or the textbook (but unusual) finding of “S1Q3T3” (S wave in lead 1, Q wave and T-wave inversion in lead 3) (figure 3)
• D-dimer: with low clinical suspicion, normal D-dimer can exclude PE
• Chest X-ray: usually normal; may show atelectasis, pleural effusion, or elevation of the hemidiaphragm
• Lower limb venous duplex ultrasound with compression: to investigate suspected concurrent DVT. Proximal DVT in suspected PE is sufficient to start anticoagulation without further investigation
• CTPA (figures 1 and 2): gold standard to confirm PE
• Ventilation-perfusion (VQ) scan: alternative to CTPA in those in whom the latter is contraindicated (e.g. renal impairment, contrast allergy) or in certain patient groups to minimise radiation exposure (e.g. pregnant patients). A VQ scan is of limited use with significant underlying lung disease, abnormal chest radiograph, left ventricular failure or congestive cardiac failure
• Echocardiogram: useful for haemodynamically unstable patients who cannot have CTPA – the presence of right ventricular dysfunction is sufficient to justify urgent thrombolysis. Signs of PE include right ventricle (RV) dilatation and hypokinesis, McConnell’s sign (segmental RV regional wall motion abnormality without apical involvement), tricuspid regurgitation and pulmonary hypertension

Figure 1: Image Source: Thrombosis Journal (2007). 10.1186, Licensed under a creative commons licence. Available for free at: https://doi.org/10.1186/1477-9560-5-20 (Accessed: 19 January 2024).

Figure 2: Image Source: Wikimedia Commons (2017). Pulmonary_embolism_CTPA, Licensed under a creative commons licence. Available for free at: https://en.wikipedia.org/wiki/Pulmonary_embolism#/media/File:Pulmonary_embolism_CTPA.JPEG (Accessed: 19 January 2024).

Image Source: Wikimedia Commons (2010). Pulm embolism, Licensed under a creative commons licence. Available for free at: https://en.wikipedia.org/wiki/Pulmonary_embolism#/media/File:Pulm_embolism.jpg (Accessed: 19 January 2024).

Diagnosing PE in pregnancy

Diagnosing acute PE in a pregnant person poses important considerations. D-dimer can be raised in pregnancy due to production by the normal placenta. Furthermore, there is consideration of radiation risks to developing breast tissue as well as the foetus. The approach to diagnosis in this special circumstance is, therefore, tailored to address these. The approach is as follows:

• D-dimer testing: not currently used in pregnancy in the UK, although this may change.

• If concurrent DVT is suspected: lower limb compression venous ultrasound is required. If a DVT is found, then anticoagulation can be started (typically LMWH or UFH; DOACs and warfarin are contraindicated in pregnancy) and no further irradiating tests are needed. Note that in the absence of clinical features of a DVT, a bilateral leg US should not be routinely requested.
• If no concurrent DVT is suspected: anticoagulation (LMWH or UFH) should be started and further investigations ordered. First, a CXR should be requested to ensure there is no underlying lung pathology that may impact the interpretation of a VQ scan. The radiation risk of a CXR to mother and foetus is trivial. VQ scans and CTPA are the next stage of investigation. If the CXR is abnormal, a CTPA is required, as a VQ scan would not be interpretable. If the CXR is normal, either VQ scan or CTPA can be used based on local availability and patient preference, after appropriate counselling regarding radiation risk. Typically, a VQ scan reduces radiation risk to maternal breast tissue and has minimally increased radiation exposure to the foetus; CTPA reduces radiation risk to the foetus but proportionally increases the risk of maternal breast cancer more than the VQ scan increases the risk of childhood cancers to the foetus. If a VQ scan is equivocal, CTPA is indicated, which has a higher specificity and sensitivity.

Management of PE

PE management is usually guided by scoring systems like the PESI (pulmonary embolism severity index) or sPESI (simplified PESI). These have categories of high, intermediate-high, intermediate-low and low risk PEs. High risk PEs (haemodynamically unstable patients) are usually thrombolysed and non-high risk PEs (haemodynamically stable) are usually treated with anticoagulation but with different durations of hospitalisation for monitoring.

Haemodynamically unstable patients

High risk, or “massive” PE is defined as acute PE with haemodynamic instability. There are three main categories for haemodynamic instability. Any single one of the following will count for the definition:

• Cardiac arrest
• Systolic BP <90 mmHg with end-organ hypoperfusion (confusion, skin clamminess, diaphoresis, mottling, oliguria, anuria, raised lactate)
• Systolic BP <90 mmHg for more than 15 minutes, with no additional contributory cause, such as sepsis, hypovolaemia or arrhythmia

For those without contraindications, urgent systemic thrombolysis is given, usually with IV alteplase (bolus then infusion). After thrombolysis, APTTR (APTT ratio) is monitored, and unfractionated heparin started when APTTR is <2.0 (normal: 0.8-1.2). This is continued until the patient is haemodynamically stable, at which point they can be switched to LMWH. If a patient is particularly frail or has relative contraindications to thrombolysis then senior input is needed, with IV UFH infusion being started until a decision about thrombolysis is made.

If there is continued deterioration despite thrombolysis, or if thrombolysis is contraindicated, surgical embolectomy or percutaneous catheter-directed therapy are options.

Haemodynamically stable patients

Anticoagulation is required for haemodynamically stable patients with PE:

• First line: rivaroxaban or apixaban
• Second line: LMWH for at least 5 days followed by dabigatran or edoxaban or warfarin with at least 5 days of LMWH bridging therapy

Mechanical interventions, e.g. IVC (inferior vena cava) filter, can be considered in patients who cannot have anticoagulation or who develop recurrent PE despite adequate anticoagulation. Thrombolytic therapy (systemic or catheter-directed) and open pulmonary embolectomy are alternatives.

Ongoing management of PE

The duration of anticoagulation therapy depends on whether or not the PE was provoked by a transient risk factor:

• Provoked: standard duration of anticoagulation is 3 months
• Unprovoked: longer-term, from 6 months to indefinite anticoagulation may be needed

A full history and examination should be performed, as well as standard blood tests. If no relevant signs or symptoms are found, no further investigations for malignancy screening are required.

If there is a plan to stop anticoagulation treatment in unprovoked PE, it is advised to consider testing for antiphospholipid antibodies and to test for hereditary thrombophilia in those with first-degree relatives who have had DVT or PE. There is no need to test for hereditary thrombophilia in those who are continuing anticoagulation.

Complications of PE

Chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of PE. Emboli are replaced by fibrous tissue, causing chronic obstruction of the pulmonary vasculature, increased pulmonary artery pressure and pulmonary hypertension. Inadequate anticoagulation, large thrombus mass, residual thrombi and recurrence of VTE may contribute to the development of CTEPH.

Patients typically present with worsening chronic breathlessness after their acute PE and signs of right heart dysfunction including cyanosis, raised JVP, loud P2 heart sound, right ventricular heave, possible tricuspid regurgitation murmur and peripheral oedema. Further testing at a specialist pulmonary hypertension centre would include right heart catheter studies, lung function testing, exercise testing and further imaging (echocardiography, CTPA, MRA, VQ scan and invasive pulmonary angiography).

Treatment options include pulmonary vasculature vasodilators, diuretics for symptom relief, anticoagulation, and more invasive options such as balloon pulmonary angioplasty and pulmonary endarterectomy.

Pulmonary infarction

Pulmonary infarction may complicate PE. Pleuritic chest pain and haemoptysis are more common in these cases. CT thorax is diagnostic – findings include a wedge-shaped focus of consolidation that may not have air bronchograms.

Paradoxical embolism

Deep vein thrombosis in the presence of right-to-left shunts (e.g. patent foramen ovale) may cause paradoxical embolism. Sites of embolisation include the cerebrovasculature causing ischaemic stroke, cardiac vessels causing myocardial infarction, gastrointestinal tract or extremities.

References

• Bennett J, Russell R, Umerah O, Vella C. Pulmonary embolism [Internet]. BMJ Best Practice. 2021 (cited January 10 2022). Available from: https://bestpractice.bmj.com/topics/en-gb/3000115 
• National Institute for Health and Care Excellence. Pulmonary Embolism. [Internet]. NICE. 2020 (cited January 10 2022). Available from: https://cks.nice.org.uk/topics/pulmonary-embolism/
• National Institute for Health and Care Excellence. Anticoagulation – oral. [Internet]. NICE. 2021 (cited January 10 2022). Available from: https://cks.nice.org.uk/topics/anticoagulation-oral/
• Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J, Roy PM, Fine MJ. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005 Oct 15;172(8):1041-6. doi: 10.1164/rccm.200506-862OC
• van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW, Kramer MH, Kruip MJ, Kwakkel-van Erp JM, Leebeek FW, Nijkeuter M, Prins MH, Sohne M, Tick LW; Christopher Study Investigators. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006 Jan 11;295(2):172-9. doi: 10.1001/jama.295.2.172
• Stavros V Konstantinides et al. ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC), European Heart Journal. 2020. 41;4:543-603. https://doi.org/10.1093/eurheartj/ehz405