Pulmonary Embolism (PE)

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Introduction

Pulmonary embolism (PE) is the luminal obstruction of one or more pulmonary arteries by an embolised venous thrombus, but can also be due to an embolised solid, liquid, or gas.¹

Venous thromboembolism (VTE) is an umbrella term encompassing both pulmonary embolism (PE) and deep vein thrombosis (DVT).¹

In the United Kingdom (UK), PE and DVT together make up the third most common cardiovascular disease (after acute myocardial infarction and stroke). PE has an overall annual incidence of 53-162 per 100,000 people. Nearly 70,000 hospital episodes of PE were reported between 2021-2022, resulting in over 35,000 admissions.²

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Aetiology

A thrombus refers to a blood clot that is formed within a blood vessel and remains in its place of origin. Embolism describes the process where the bloodstream carries a detached intravascular solid, liquid, or gaseous mass from its origin to a distant site.¹

Most PEs originate as thrombi due to deep vein thrombosis, most frequently in the calf veins.³

Other causes include:³

Fat embolism
Air embolism
Amniotic fluid embolism
Septic emboli
De novo thrombosis (rare)

Pathophysiology

In a PE, an embolus detaches from its origin and embolises to the pulmonary arteries through the systemic venous system and the right heart, finally causing luminal obstruction of one or more pulmonary arteries.^3,5

Pathological consequences of pulmonary embolism:^3,5

Ventilation/perfusion mismatch → impaired gaseous exchange → hypoxaemia (type 1 respiratory failure) and tachypnoea
Pulmonary arterial hypertension (due to increased pulmonary vasculature resistance) → right ventricular overload +/- dysfunction
Pleural and lung inflammation and infarction → pleuritic chest pain +/- haemoptysis

The diagnosis of PE can be challenging, and these pathological changes do not always manifest with the above clinical features.

Saddle pulmonary embolism — **Figure 1**. Gross specimen showing a saddle pulmonary embolism

Risk factors

Risk factors for PE include and are not limited to:^3,4,5

Diagnosis of DVT: ~45-50% of people with PE have concurrent DVT
Increasing age
Previous VTE

The Virchow’s triad for VTE:^3,4,5

Venous stasis: prolonged immobilisation (e.g. bed rest >5 days, major surgery within the last 2 months, recent trauma or fracture, paralysis of the lower limb, long-haul flights), venous insufficiency of the lower limb.
Hypercoagulable state: active malignancy, pregnancy and postnatal period, thrombophilia (e.g. antiphospholipid syndrome, factor V Leiden mutation), use of combined hormonal contraception and oral hormone replacement therapy.
Endothelial injury: trauma, surgery, venous harvest, cigarette smoking, obesity.

Concurrent DVT, prolonged immobilisation and previous VTE events are strong risk factors for PE (they form part of the 2-level PE Wells score).

Clinical features

The signs and symptoms of pulmonary embolism are highly non-specific, making PE challenging to diagnose.

History

Typical symptoms of PE may include:^2,3,4,9

Dyspnoea: the most common feature
Tachypnoea (~20-40% cases)
Pleuritic chest pain (~40% of cases)
Features of concurrent DVT (typically unilateral red, painful swollen leg)
Haemoptysis

Other possible symptoms include:^2,3,4,9

Retrosternal chest pain (due to right ventricular ischaemia)
Cough

Clinical examination

Patients with a suspected PE require a comprehensive respiratory and cardiovascular examination. Acutely unwell patients will require an ABCDE approach.

Typical clinical findings on examination may include:^2,3,4,9

Tachycardia
Tachypnoea
Hypoxia
Low-grade fever
Pleural rub
Gallop rhythm, a wide split-second heart sound and tricuspid regurgitant murmur.

Massive pulmonary embolism

Features of a massive PE include:^2,3,4,9

Haemodynamic instability: hypotension and cardiogenic shock
Presyncope/syncope
Elevated jugular venous pressure (JVP)

Investigations

Bedside investigations

A 12-lead ECG should always be performed in the context of chest pain. In the context of PE, it should be used to exclude possible differential diagnoses (e,g. acute coronary syndrome). ECG features alone are not diagnostic of PE.

Possible ECG findings include:^4,11

Sinus tachycardia: the most common finding
Right ventricular strain pattern: T wave inversion in anterior leads (V1-V4) +/- inferior leads (II, III, aVF)
Right bundle branch block (RBBB)
Right axis deviation (RAD)
The classic ‘S1Q3T3’ ECG change is only seen in <20% patients – large S wave in lead I, large Q wave in lead III, and inverted T wave in lead III

Laboratory investigations

Relevant laboratory investigations include:^2,3

D-dimer levels: often raised, typically >500 ng/mL (see below)
Full blood count (FBC): may demonstrate leucocytosis due to acute inflammation but is non-specific
Urea and electrolytes (U&E): often unremarkable, baseline renal function results can be used to guide investigations and treatment
Liver function tests (LFTs): often unremarkable, they can be used to guide treatment
Cardiac biomarkers (troponin and BNP) are not used in diagnosing PE but can provide prognostic information.
Coagulation studies: should be established before starting treatment and can guide treatment.

D-dimer

D-dimer test has a high sensitivity but low specificity for VTE. Many conditions can result in an elevated D-dimer in the absence of VTE:^2,13

Pregnancy
Malignancy
Liver disease
Severe infection or inflammatory disease
Disseminated intravascular coagulation (DIC)
Recent trauma/surgery/hospitalised patients

In these patients, D-dimer testing has no value in diagnosing VTE.

Imaging

Chest X-ray

Chest X-ray should be used to exclude possible differential diagnoses (e.g. pneumothorax and pneumonia). Most patients with PE have a normal chest X-ray.¹⁰

Possible chest X-ray findings in PE include:¹⁰

Wedge-shaped pulmonary infarction: wedge-shaped opacification without air bronchograms
Atelectasis
Pleural effusion
Raised hemidiaphragm

CTPA (CT pulmonary angiogram)

CTPA is the preferred investigation for the definitive diagnosis of PE.

Diagnosis of PE is confirmed by direct visualisation of a thrombus within a pulmonary artery lumen.

A large pulmonary embolism at the bifurcation of the pulmonary artery (saddle embolism). — **Figure 2**. CTPA showing a large pulmonary embolism at the bifurcation of the pulmonary artery (saddle embolism).

Alternative to CTPA in the diagnosis of PE

NICE recommends ventilation-perfusion (V/Q) planar scan or SPECT as the investigation of choice instead of CTPA in the following patients:¹²

Severe renal impairment (eGFR < 30 mL/min/1.73m²)
Allergic to contrast media
At high risk from irradiation (e.g. pregnancy)

Both V/Q planar scan and SPECT have a lower effective radiation dose (~2 mSv compared to 3-10 mSv) compared to CTPA.²

Echocardiography

In haemodynamically unstable patients who are unsuitable for CTPA, echocardiography is recommended to aid the diagnosis of a suspected PE.²

Echocardiography may show signs of right ventricular dysfunction that is suggestive of PE, including:

Abnormal right ventricular ejection pattern – 60/60 sign
McConnel sign – reduced right ventricular free wall contractility compared with the apex
Right ventricular dilation and hypokinesis

Negative echocardiography does NOT exclude a PE. A 40-50% negative predictive value for PE has been reported.²

Management

General approach

Acutely unwell patients require an ABCDE approach.

If clinical suspicion of PE is low, the pulmonary embolism rule-out criteria should be used.¹²

If PE is suspected, perform a two-level PE Wells score without using pulmonary embolism rule-out criteria. While NICE (The National Institute for Health and Care Excellence) guidelines advocate using the Wells score to aid diagnosis, ESC (European Society of Cardiology) guidelines advocate the revised Geneva rule.

Pulmonary Embolism Rule-out Criteria (PERC)

The PERC rule should only be used if the clinical suspicion for PE is low (based on medical history, examination, and investigations) to avoid the overuse of diagnostic testing for PE.¹²

The PERC rule states that if ALL the following criteria are ABSENT, it reduces the probability of PE to < 2%.¹² In such cases, an alternative diagnosis should be considered.

Age ≥ 50 y/o
HR ≥ 100 bpm
SpO2 < 95% on room air
Unilateral leg swelling
Haemoptysis
Recent surgery/trauma ≤4 weeks ago requiring general anaesthesia
Previous DVT / PE
Hormone use (oral contraceptives/hormone replacement/estrogenic hormones)

Two-level PE Wells score-guided investigations

Table 1. The Two-level Wells score for PE.¹²

Clinical feature	Points
Clinical signs and symptoms of DVT (minimum of leg swelling and pain with palpation of the deep veins)	3
An alternative diagnosis is less likely than PE	3
Heart rate more than 100 beats per minute	1.5
Immobilisation for more than 3 days or surgery in the previous 4 weeks	1.5
Previous DVT/PE	1.5
Haemoptysis	1
Malignancy (on treatment, treated in the last 6 months, or palliative)	1

Clinical probability
PE likely	More than 4 points
PE unlikely	4 points or less

PE is likely (Wells >4)

Offer immediate computed tomography pulmonary angiogram (CTPA).

If CTPA cannot be done immediately, offer interim therapeutic anticoagulation until a scan is performed.

If CTPA is positive (PE identified):

Start or continue therapeutic anticoagulation treatment
If anticoagulation treatment is contraindicated, consider mechanical intervention

If CTPA is negative (PE not identified):

Consider a proximal leg vein ultrasound scan if DVT is suspected
If DVT is not suspected → PE is not likely, stop any interim therapeutic anticoagulation but NOT prophylactic anticoagulation for primary prevention and long-term anticoagulation for secondary prevention, consider alternative diagnosis

If PE is likely, why not D-dimer?

Remember, the D-dimer test has low specificity for VTE, making it unsuitable for use in cases where a PE is likely because a positive result does not confirm the diagnosis of PE due to the potential for false positives in other conditions.

PE is unlikely (Wells ≤4)

Offer a D-dimer test with results available within 4 hours.

If the D-dimer test result cannot be obtained within 4 hours, start interim therapeutic anticoagulation.

If the D-dimer test is positive:

Offer immediate CTPA and give interim therapeutic anticoagulation if there is a delay.

If the D-dimer test is negative:

PE is not likely
Stop any interim therapeutic anticoagulation but NOT prophylactic anticoagulation and long-term anticoagulation
Consider an alternative diagnosis

If PE is unlikely, why use D-dimer?

Remember, the D-dimer test has high sensitivity for VTE, so if the D-dimer is negative PE can be excluded without the patient being exposed to radiation from a CTPA.

Management of confirmed PE

PE with haemodynamic instability

Offer continuous UFH (unfractionated heparin) infusion, and consider thrombolytic therapy:^2,12

IV tissue plasminogen activator (tPA) (e.g. alteplase) is often used
Catheter-directed thrombolysis
Open pulmonary embolectomy

Risk assessment (outpatient vs inpatient)

NICE suggest that outpatient treatment for low-risk PE can be considered, using a validated risk stratification tool to determine suitability:^12,14

NICE guidelines did not include a specific tool or scoring system.
The British Thoracic Society (BTS) guidelines support the use of the Pulmonary Embolism Severity Index (PESI) score

A key requirement for outpatient treatment is being haemodynamically stable.

Patients with intermediate-risk or high-risk PE should be considered for in-patient treatment.

Anticoagulation

In haemodynamically stable PE, management involves anticoagulation therapy:^2,12

First line: apixaban or rivaroxaban, both direct oral anticoagulants (DOACs)
Second line: low molecular weight heparin (LMWH) followed by dabigatran/edoxaban OR LMWH followed by warfarin

The choice of anticoagulants varies in specific patient populations:^2,12,14

Pregnant: LMWH only (DOACs and warfarin contraindicated)
Active cancer: DOAC preferred over LMWH
Severe renal impairment (eGFR < 15 mL/min/1.73m²): UFH or dose-adjusted LMWH
Antiphospholipid syndrome (triple positive): initial LMWH and warfarin followed by warfarin monotherapy
All forms of anticoagulation contraindicated: inferior vena cava (IVC) filter

NICE recommends that all patients should have anticoagulation for at least three months. Further anticoagulation is based on the patient’s risk of VTE recurrence and risk of bleeding (ORBIT score is recommended to help assess the risk of bleed).¹²

As a rule of thumb:¹²

If VTE was provoked → 3 months of anticoagulation
If VTE was unprovoked → 6 months of anticoagulation
If there is active cancer → 3-6 months of anticoagulation

Provoked vs unprovoked PE

Provoked PE is associated with a recent (within three months) and transient major risk factor (there is no clear-cut guidance, but NICE CKS give examples of significant immobility, surgery, trauma, pregnancy or puerperium, or use of hormonal therapy).¹²

Unprovoked PE occurs in the absence of a recent (within three months) major clinical risk factor in a person who is not using hormonal therapy.¹²

It is worth noting that the ESC guidelines no longer support using the terms ‘provoked’ and ‘unprovoked’. They state that they are potentially misleading and unhelpful when making a decision about the duration of anticoagulation.²

Complications

Short-term complications of PE include:

Sudden cardiac arrest or death can result from ventricular collapse due to massive embolism and occlusion of the pulmonary vasculature
Pulmonary infarction due to obstruction of arterial blood supply, more common when distal arteries are occluded
Right ventricular infarction, often secondary to pulmonary hypertension and haemodynamic overload
Atelectasis
Exudative pleural effusion

Long-term complications of PE include:^3,4

Increased risk of recurrence, history of previous VTE is a significant risk factor for future VTEs
Chronic thromboembolic pulmonary hypertension (CTEPH) occurs where fibrotic tissue replaces residual emboli causing chronic obstruction of the pulmonary vasculature, and hence pulmonary hypertension

CTEPH should be excluded in patients with persistent dyspnoea and poor physical performance three to six months after a PE.^3,4

Key points

Pulmonary embolism (PE) results from a dislodged thrombus occluding the pulmonary vasculature. It is potentially life-threatening if not appropriately identified and treated.
PE shares the same risk factors as DVT, and they can be classified according to Virchow’s triad (venous stasis, hypercoagulable state, endothelial injury).
Clinical features of PE are highly non-specific; an acute onset makes it more likely, and dyspnoea and tachypnoea are considered the most common presenting features.
When a PE is suspected, the two-level PE Wells score guides the diagnostic and management approach.
CT Pulmonary Angiogram (CTPA) is considered the gold standard diagnostic tool.
The mainstay management of PE involves anticoagulation therapy, usually direct oral anticoagulants (DOACs) for at least 3 months.
Massive PE or PE with haemodynamic instability carries a high mortality and should be treated aggressively with thrombolytic agents.

Reviewers

Dr Joelle Azzopardi

Respiratory consultant

Dr Adriano Buontempo

Lecturer in Clinical Communication Skills

Editor

Dr Chris Jefferies

References

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