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Peripheral Artery Disease: causes and consequences

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Introduction to Pulmonary Embolism

This section introduces PE, its clinical presentation, risk assessment scores and diagnostic strategies

 

PE is a potential cardiovascular emergency caused by part of a thrombus, usually dislodged from a DVT (subsequently called an embolus), passing into the pulmonary circulation and preventing blood flow to the lungs

  • PE is the most common reason for preventable hospital death1
  • Long-term complications include CTEPH, which, although rare, can have serious consequences such as progressive pulmonary hypertension leading to right heart failure2,3
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The pathway of a pulmonary embolus from the lower part of the body: inferior vena cava, to right atrium, to right ventricle, to the pulmonary artery. This might eventually obstruct blood flow to the lung. Patients with DVT are at risk of PE, a life-threatening event

 

PE is a potentially life-threatening condition, and in severe cases the occurrence of circulatory collapse and cardiac arrest may result in sudden death

  • Early fatality occurs in up to 15% of patients;4 therefore, rapid diagnosis is crucial
  • The diagnosis of PE, however, may be missed because of its non-specific clinical symptoms
  • Similar to DVT, PE is often asymptomatic,5 and approximately 30% of cases of PE are unprovoked (idiopathic)4,6

 

Common signs and symptoms of PE:4

  • Dyspnoea
  • Pleuritic chest pain
  • Cough
  • Substernal chest pain
  • Fever
  • Haemoptysis
  • Syncope
  • Unilateral leg pain
  • Signs of DVT (unilateral extremity swelling)

 

Around 80% of patients with PE have signs of DVT, and approximately 50% of patients with proven proximal DVT have an associated PE.7

 

None of the above symptoms is specifically diagnostic of PE. The European Society of Cardiology (ESC) guidelines recommend the use of a stepwise diagnostic algorithm that:4

  • Combines several evidence-based diagnostic strategies
  • Stratifies patients according to their risk of early death based on clinical symptoms, as shown in the figures below
  • Has been validated in both the emergency ward and primary care settings
Classification of patients with acute PE based on early mortality risk4
Early mortality risk Risk parameters and scores
  Cardiogenic shock or hypotension PESI class III–V or sPESI >1a Signs of right ventricular dysfunction on an imaging test Elevated cardiac biomarkers
High + (+)b + (+)b
Intermediate high + Both positive
Intermediate low + Either one (or none) positivec
Low Assessment optional; if assessed, both negativec

aPESI Class III–V: moderate to very high 30-day mortality risk; sPESI ≥1 point(s): high 30-day mortality risk. bNeither calculation of PESI (or sPESI) nor laboratory testing are considered necessary in patients with hypotension or cardiogenic shock. cPatients with PESI Class I–II/sPESI of 0, and elevated cardiac biomarkers/signs of right ventricular dysfunction, are to be considered as intermediate-low risk

 

High-risk PE is usually suspected if cardiogenic shock and/or hypotension are present. Once stabilized, suspected ‘high-risk’ PE patients can undergo CT pulmonary angiography to confirm or dismiss the diagnosis of PE. If PE is not found to be the cause of haemodynamic instability, other causes (such as ACS) should be investigated.4

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European Society of Cardiology algorithm for patients with suspected high-risk PE

Adapted from Konstantinides et al.4 aIncludes cases in which the patient’s condition is so critical that it only allows bedside diagnostic tests; bapart from the diagnosis of RV dysfunction, a bedside transthoracic echocardiogram may, in some cases, directly confirm PE by visualizing mobile thrombi in the right heart chambers; cthrombolysis; alternatively, surgical embolectomy or catheter-directed treatment RV, right ventricular

Patients categorized as having ‘low-to-intermediate’ risk PE require further risk stratification using clinical judgement or a clinical prediction rule such as the Wells’ score.4

  • If the clinical probability of PE is high, a confirmatory CT pulmonary angiography scan should be performed
  • Patients with a ‘low/intermediate’ clinical probability of PE should undergo a D-dimer test before imaging
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European Society of Cardiology algorithm for patients with suspected non-high-risk PE

Adapted from Konstantinides et al.4 aTwo alternative classification schemes may be used for clinical probability assessment, i.e. a three-level scheme (clinical probability defined as low, intermediate or high) or a two-level scheme (PE unlikely or PE likely);btreatment refers to anticoagulation treatment for PE; cCT pulmonary angiogram is considered to be diagnostic of PE if it shows PE at the segmental or more proximal level; din case of a negative CT pulmonary angiogram in patients with a high clinical probability, further investigation may be considered before withholding PE-specific treatment

Scoring systems used in clinical practice include several key risk factors and markers for PE based on patient history and presentation. The Wells’ score is commonly used to predict clinical probability of PE.4,8

Wells’ score for prediction of PE.4,8 A total score >6 indicates a high probability of a PE, a score of 2−6 moderate probability and a score <2 low probability4
ParameterScore
Clinically suspected DVT3
Alternative diagnosis less likely than PE3
Rapid heart rate1.5
Immobilization within past 4 weeks1.5
History of DVT1.5
Haemoptysis1
Malignancy1

Patients with a high likelihood of PE by the Wells’ score should undergo diagnostic imaging. Those with a low/moderate likelihood should have a D-dimer test; if the latter is positive, imaging should be performed.4

 

CT pulmonary angiography is the preferred method of diagnostic imaging in patients with a clinical risk score indicative of PE because it provides a high resolution image and is as accurate and less invasive compared with pulmonary angiography, the previous ‘gold standard’.4

 

A V/Q scan is another established diagnostic test.4

  • Exposes patients to significantly lower levels of radiation than CT pulmonary angiography
  • Preferred in pregnant and young patients or those with severe renal impairment
  • A V/Q scan indicating a high probability of PE provides sufficient evidence for the initiation of treatment but a low probability scan does not rule out PE – further diagnostic tests may be required

 

In non-high-risk patients, further risk stratification is necessary once a PE diagnosis has been confirmed. The ESC guidelines recommend use of the PESI or sPESI score to further risk-stratify patients.4

  • Intermediate-risk patients are identified as PESI Class III or higher or sPESI ≥1, and should be further stratified by assessment of right ventricular function and cardiac biomarker levels4
    • Patients with normal right ventricular function and/or normal cardiac biomarkers are stratified as intermediate-low risk
    • Patients with evidence of right ventricular dysfunction and elevated cardiac biomarkers (especially elevated cardiac troponin levels) should be classified as intermediate-high risk
    • Intermediate-high-risk patients should be monitored closely for clinical deterioration and may require rescue reperfusion therapy if haemodynamic decompensation occurs

 

The ESC guidelines recommend that low-risk patients should be considered for early discharge and home treatment providing proper outpatient care and anticoagulant treatment can be provided.4

Risk stratification using PESI and sPESI scores4
Parameter PESI sPESI
Age Points = age in years If aged >80 years old = 1 point
Male sex +10 points
Cancer +30 points 1 point
Chronic heart failure +10 points 1 point
Chronic pulmonary disease +10 points 1 point
Pulse rate ≥110 beats per minute +20 points 1 point
Systolic blood pressure
<100 mmHg
+30 points 1 point
Respiratory rate
>30 breaths/min
+20 points
Temperature <36°C +20 points
Altered mental status +60 points
Arterial oxyhaemoglobin saturation <90% +20 points 1 point
  Class I: ≤65 points
Very low 30-day mortality risk (0–1.6%)
Class II: 66–85 points
Low mortality risk (1.7–3.5%)
0 points = low risk
Low 30-day mortality risk (1.0%)
(95% CI 0–2.1%)
  Class III: 86–105 points
Moderate mortality risk
(3.2–7.1%)
Class IV: 106–125 points
High mortality risk
(4.0–11.4%)
Class V: >125 points
Very high mortality risk
(10.0–24.5%)
≥1 point(s) = not low risk
30-day mortality risk
(10.9%)
(95% CI 8.5–13.2%)

CI, confidence interval

 

The 2018 British Thoracic Society (BTS) guidelines for outpatient management of PE, recommend treatment with either LMWH plus dabigatran or edoxaban, or a single NOAC (rivaroxaban or apixaban); with preference given to a single NOAC (rivaroxaban or apixaban) regimen to minimize potential confusion over dosing and administration. These guidelines also provide guidance on evaluating patients with PE for outpatient management.9

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BTS guidelines for the identification of patients with PE suitable for outpatient management9

*Patients with cancer or those who are pregnant or within 6 weeks’ post-partum may be considered for outpatient management

References
  • Geerts WH, Bergqvist D, Pineo GF et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008;133:381S–453S. Geerts WH, Bergqvist D, Pineo GF et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008;133:381S–453S. Return to content
  • Pengo V, Lensing AWA, Prins MH et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004;350:2257–2264. Return to content
  • Lang I. Advances in understanding the pathogenesis of chronic thromboembolic pulmonary hypertension. Br J Haematol 2010;149:478–483. Return to content
  • Konstantinides SV, Torbicki A, Agnelli G et al. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014;35:3033–3069. Return to content
  • Girard P, Musset D, Parent F et al. High prevalence of detectable deep venous thrombosis in patients with acute pulmonary embolism. Chest 1999;116:903–908. Return to content
  • Torbicki A, Perrier A, Konstantinides S et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29:2276–2315. Return to content
  • Tapson VF. Acute pulmonary embolism. N Engl J Med 2008;358:1037–1052. Return to content
  • Wells PS, Anderson DR, Rodger M et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 2000;83:416–420. Return to content
  • Howard L, Barden S, Condliffe R et al. British Thoracic Society guideline for the initial outpatient management of pulmonary embolism (PE). Thorax 2018;73:ii1–ii29. Return to content

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