Pulmonary embolism (PE) is a condition in which one or more emboli, usually arising from a thrombus formed in the veins, are obstruct the pulmonary arteries, causing respiratory dysfunction.

We know from experience that few patients (around 10%) present with the medical student textbook triad of pleuritic chest pain, dyspnoea and haemoptysis. Pulmonary embolism can be difficult to diagnose as it can present with virtually any cardiorespiratory symptom/sign depending on its location and size.

So which features make pulmonary embolism more likely?

The PIOPED study¹ in 2007 looked at the frequency of different symptoms and signs in patients who were diagnosed with pulmonary embolism.

The relative frequency of common clinical signs is shown below:

• Tachypnea (respiratory rate >20/min) - 96%
• Crackles - 58%
• Tachycardia (heart rate >100/min) - 44%
• Fever (temperature >37.8°C) - 43%

It is interesting to note that the Well's criteria for diagnosing a PE use tachycardia rather than tachypnoea.

Pulmonary embolism rule-out criteria (PERC)

NICE updated their guidelines on the investigation and management of venous thromboembolism (VTE) in 2020. One of the key changes was the use of the pulmonary embolism rule-out criteria (the PERC rule)

• a copy of criteria can be found in the image below
• all the criteria must be absent to have negative PERC result, i.e. rule-out PE
• this should be done when you think there is a low pre-test probability of PE, but want more reassurance that it isn't the diagnosis
  • this low probability is defined as < 15%, although it is clearly difficult to quantify such judgements
• a negative PERC reduces the probability of PE to < 2%
• if your suspicion of PE is greater than this then you should move straight to the 2-level PE Wells score, without doing a PERC

2-level PE Wells score

If a PE is suspected a 2-level PE Wells score should be performed:


Clinical probability simplified scores

• PE likely - more than 4 points
• PE unlikely - 4 points or less

If a PE is 'likely' (more than 4 points)

• arrange an immediate computed tomography pulmonary angiogram (CTPA)
• If there is a delay in getting the CTPA then interim therapeutic anticoagulation should be given until the scan is performed.
  • interim therapeutic anticoagulation used to mean giving low-molecular-weight heparin
  • NICE updated their guidance in 2020. They now recommend using an anticoagulant that can be continued if the result is positive.
  • this means normally a direct oral anticoagulant (DOAC) such as apixaban or rivaroxaban

- if the CTPA is positive then a PE is diagnosed

• if the CTPA is negative then consider a proximal leg vein ultrasound scan if DVT is suspected

If a PE is 'unlikely' (4 points or less)

• arranged a D-dimer test
  • if positive arrange an immediate computed tomography pulmonary angiogram (CTPA). If there is a delay in getting the CTPA then give interim therapeutic anticoagulation until the scan is performed
  • if negative then PE is unlikely - stop anticoagulation and consider an alternative diagnosis

CTPA or V/Q scan?

The consensus view from the British Thoracic Society and NICE guidelines is as follows:

• CTPA is now the recommended initial lung-imaging modality for non-massive PE. Advantages compared to V/Q scans include speed, easier to perform out-of-hours, a reduced need for further imaging and the possibility of providing an alternative diagnosis if PE is excluded
• if the CTPA is negative then patients do not need further investigations or treatment for PE
• V/Q scanning may be used initially if appropriate facilities exist, the chest x-ray is normal, and there is no significant symptomatic concurrent cardiopulmonary disease. V/Q scanning is also the investigation of choice if there is renal impairment (doesn't require the use of contrast unlike CTPA)

Some other points

D-dimers

• sensitivity = 95-98%, but poor specificity
• age-adjusted D-dimer levels should be considered for patients > 50 years

ECG

• the classic ECG changes seen in PE are a large S wave in lead I, a large Q wave in lead III and an inverted T wave in lead III - 'S1Q3T3'. However, this change is seen in no more than 20% of patients
• right bundle branch block and right axis deviation are also associated with PE
• sinus tachycardia may also be seen

Chest x-ray

• a chest x-ray is recommended for all patients to exclude other pathology
• however, it is typically normal in PE
• possible findings include a wedge-shaped opacification

V/Q scan

• sensitivity of around 75% and specificity of 97%
• other causes of mismatch in V/Q include old pulmonary embolisms, AV malformations, vasculitis, previous radiotherapy
• COPD gives matched defects

CTPA

• peripheral emboli affecting subsegmental arteries may be missed

1. Clinical Characteristics of Patients with Acute Pulmonary Embolism(Data from PIOPED II) Am J Med. Oct 2007; 120(10): 871879.

All patients with symptoms or signs suggestive of a PE should have a history taken, examination performed and a chest x-ray to exclude other pathology.

If a PE is still suspected a two-level PE Wells score should be performed:


Clinical probability simplified scores

• PE likely - more than 4 points
• PE unlikely - 4 points or less

If a PE is 'likely' (more than 4 points) arrange an immediate computed tomography pulmonary angiogram (CTPA). If there is a delay in getting the CTPA then give low-molecular-weight heparin until the scan is performed.

If a PE is 'unlikely' (4 points or less) arranged a D-dimer test. If this is positive arrange an immediate computed tomography pulmonary angiogram (CTPA). If there is a delay in getting the CTPA then give low-molecular-weight heparin until the scan is performed.

If the patient has an allergy to contrast media or renal impairment a V/Q scan should be used instead of a CTPA.

NICE updated their guidelines on the management of venous thromboembolism (VTE) in 2020. Some of the key changes include recommending the following:

• the use of direct oral anticoagulants (DOACs) as first-line treatment for most people with VTE
• the use of DOACs in patients with active cancer, as opposed to low-molecular weight heparin as was the previous recommendation
• outpatient treatment in low-risk pulmonary embolism (PE) patients
• routine cancer screening is no longer recommended following a VTE diagnosis

Outpatient treatment in low-risk PE patients

Deep vein thrombosis has for a long time been treated on an outpatient condition. In contrast, patients with any form of PE were typically admitted. However, in recent years patients with a new diagnosis of PE who are deemed low-risk are now increasingly managed as outpatients. NICE formally supported this approach in their latest guidance.

• NICE recommends using a 'validated risk stratification tool' to determine the suitability of outpatient treatment.
  • no guidance is given as to what tool should be used
  • the 2018 British Society guidelines support the use of the Pulmonary Embolism Severity Index (PESI) score
• key requirements would clearly be haemodynamic stability, lack of comorbidities and support at home

Anticogulant therapy

The cornerstone of VTE management is anticoagulant therapy. This was historically done with warfarin, often preceded by heparin until the INR was stable. However, the development of DOACs, and an evidence base supporting their efficacy, has changed modern management.

Choice of anticoagulant

• the big change in the 2020 guidelines was the increased use of DOACs
• apixaban or rivaroxaban (both DOACs) should be offered first-line following the diagnosis of a PE
  • instead of using low-molecular weight heparin (LMWH) until the diagnosis is confirmed, NICE now advocate using a DOAC once a diagnosis is suspected, with this continued if the diagnosis is confirmed
  • if neither apixaban or rivaroxaban are suitable then either LMWH followed by dabigatran or edoxaban OR LMWH followed by a vitamin K antagonist (VKA, i.e. warfarin)
• if the patient has active cancer
  • previously LMWH was recommended
  • the new guidelines now recommend using a DOAC, unless this is contraindicated
• if renal impairment is severe (e.g. < 15/min) then LMWH, unfractionated heparin or LMWH followed by a VKA
• if the patient has antiphospholipid syndrome (specifically 'triple positive' in the guidance) then LMWH followed by a VKA should be used

Length of anticoagulation

• all patients should have anticoagulation for at least 3 months
• continuing anticoagulation after this period is partly determined by whether the VTE was provoked or unprovoked
  • a provoked VTE is due to an obvious precipitating event e.g. immobilisation following major surgery. The implication is that this event was transient and the patient is no longer at increased risk
  • an unprovoked VTE occurs in the absence of an obvious precipitating event, i.e. there is a possibility that there are unknown factors (e.g. mild thrombophilia) making the patient more at risk from further clots
• if the VTE was provoked the treatment is typically stopped after the initial 3 months (3 to 6 months for people with active cancer)
• if the VTE was unprovoked then treatment is typically continued for up to 3 further months (i.e. 6 months in total)
  • NICE recommend that whether a patient has a total of 3-6 months anticoagulant is based upon balancing a person's risk of VTE recurrence and their risk of bleeding
  • the HAS-BLED score can be used to help assess the risk of bleeding
  • NICE state: 'Explain to people with unprovoked DVT or PE and a low bleeding risk that the benefits of continuing anticoagulation treatment are likely to outweigh the risks. '. The implication of this is that in the absence of a bleeding risk factors, patients are generally better off continuing anticoagulation for a total of 6 months

PE with haemodynamic instability

Thrombolysis

• thrombolysis is now recommended as the first-line treatment for massive PE where there is circulatory failure (e.g. hypotension)
• other invasive approaches should be considered where appropriate facilities exist

Patients who have repeat pulmonary embolisms, despite adequate anticoagulation, may be considered for inferior vena cava (IVC) filters. These work by stopping clots formed in the deep veins of the leg from moving to the pulmonary arteries. IVC filter use is currently supported by NICE but other studies suggest a weak evidence base - please see the link for more details.