What is the diagnosis and treatment of pulmonary embolism (PE)?

Diagnosis and Treatment of Pulmonary Embolism (PE)

The diagnosis of pulmonary embolism should follow a stepwise approach using clinical probability assessment, D-dimer testing, and imaging studies, while treatment should be initiated with immediate anticoagulation, preferably with direct oral anticoagulants (DOACs) in eligible patients. 1

Diagnostic Algorithm

• Use clinical prediction rules (Wells score, Geneva score) or clinical judgment to determine the pre-test probability of PE 1
• In patients with low or intermediate clinical probability (PE-unlikely):
  • Measure D-dimer with a highly sensitive assay 1
  • If D-dimer is normal, PE can be safely excluded without further testing 2
  • If D-dimer is elevated, proceed to imaging 2
• In patients with high clinical probability (PE-likely):
  • Proceed directly to imaging without D-dimer testing 2
  • Do not measure D-dimers as a normal result does not safely exclude PE 2

Imaging Options

• Computed Tomography Pulmonary Angiography (CTPA):
  • First-line imaging modality for suspected PE 1
  • Accept PE diagnosis if CTPA shows segmental or more proximal filling defect in patients with intermediate or high clinical probability 2
  • Reject PE diagnosis if CTPA is normal in patients with low or intermediate clinical probability 2
• Ventilation/Perfusion (V/Q) Scan:
  • Alternative to CTPA, especially in younger patients and pregnancy due to lower radiation exposure 3
  • Reject PE diagnosis if perfusion scan is normal 2
  • A low probability V/Q scan can rule out PE, while a high probability scan confirms it 3
• Compression Ultrasonography (CUS):
  • Accept diagnosis of venous thromboembolism (VTE) if CUS shows proximal deep vein thrombosis (DVT) in a patient with clinical suspicion of PE 2

Risk Stratification

• Stratify patients with confirmed PE based on hemodynamic stability to identify those at high risk of early mortality 2
• In hemodynamically stable patients, further stratify PE into intermediate and low-risk categories 2
• Risk factors to consider include:
  • Age, male sex, cancer, heart failure, chronic lung disease 1
  • Vital signs: heart rate >110/min, systolic BP <100 mmHg, respiratory rate ≥30/min, temperature <36°C, altered mental status, SaO₂ <90% 1
  • Right ventricular dysfunction on imaging or elevated cardiac biomarkers 1

Treatment in the Acute Phase

High-Risk PE (with hemodynamic instability)

• Administer systemic thrombolytic therapy immediately 2
• If thrombolysis is contraindicated or has failed, perform surgical pulmonary embolectomy 2
• Initiate intravenous unfractionated heparin without delay, including a weight-adjusted bolus 1
• Administer oxygen to correct hypoxemia 4
• Correct systemic hypotension to prevent progression of right ventricular failure 4

Intermediate and Low-Risk PE

• When initiating oral anticoagulation in a PE patient eligible for a DOAC (apixaban, dabigatran, edoxaban, or rivaroxaban), a DOAC should be preferred over vitamin K antagonists. 2, 1
• If parenteral anticoagulation is initiated in a patient without hemodynamic instability, prefer low-molecular-weight heparin (LMWH) or fondaparinux over unfractionated heparin 2
• Administer rescue thrombolytic therapy to patients with hemodynamic deterioration on anticoagulation treatment 2
• Do not routinely administer systemic thrombolysis as primary treatment in patients with intermediate or low-risk PE 2

Special Considerations

• Do not use DOACs in patients with:
  • Severe renal impairment 2
  • Antiphospholipid antibody syndrome 2
• Do not routinely use inferior vena cava filters 2
• For pregnant women:
  • Administer therapeutic, fixed doses of LMWH based on early pregnancy weight 2
  • Do not use DOACs during pregnancy or lactation 2
  • Do not insert a spinal or epidural needle within 24 hours of the last LMWH dose 2
  • Do not administer LMWH within 4 hours of removal of an epidural catheter 2

Duration of Anticoagulation

• Administer therapeutic anticoagulation for >3 months to all patients with PE 2
• Discontinue therapeutic oral anticoagulation after 3 months in patients with first PE secondary to a major transient/reversible risk factor 2
• Continue oral anticoagulant treatment indefinitely in patients with:
  • Recurrent VTE (at least one previous episode of PE or DVT) not related to a major transient or reversible risk factor 2
  • Antiphospholipid antibody syndrome (use vitamin K antagonist) 2
• In patients receiving extended anticoagulation, reassess drug tolerance, adherence, hepatic and renal function, and bleeding risk at regular intervals 2

Post-PE Follow-up

• Routinely re-evaluate patients 3-6 months after acute PE 1
• Implement an integrated model of care to ensure optimal transition from hospital to ambulatory care 2
• Refer symptomatic patients with mismatched perfusion defects on V/Q scan beyond 3 months after acute PE to a pulmonary hypertension/CTEPH expert center 2

Common Pitfalls and Caveats

• Single subsegmental PE findings on CTPA may represent false positives - consider discussing with radiologist or seeking second opinion 2
• Do not perform CT venography as an adjunct to CTPA 2
• Do not perform MRA to rule out PE 2
• Consider using age-adjusted or clinical probability-adjusted D-dimer cutoffs as an alternative to fixed cutoffs to reduce unnecessary imaging 1
• Follow-up imaging is not routinely recommended in asymptomatic patients 2