What are the indications for thrombolysis in submassive pulmonary embolism (PE)?

Indications for Thrombolysis in Submassive Pulmonary Embolism

Thrombolytic therapy should be considered in patients with submassive PE who have evidence of right ventricular dysfunction and are at low risk of bleeding, particularly if they show signs of clinical deterioration after starting anticoagulation. 1

Definition of Submassive PE

Submassive PE (also called intermediate-risk PE) is characterized by:

• Normal blood pressure (systolic BP ≥90 mmHg)
• Evidence of right ventricular (RV) dysfunction on imaging or elevated cardiac biomarkers
• Absence of shock or hypotension

Specific Indications for Thrombolysis in Submassive PE

Primary Indications:

• Evidence of RV dysfunction on echocardiography (RV hypokinesis or estimated RVSP >40 mmHg) 1
• Elevated cardiac biomarkers:
  • Troponin above borderline value
  • BNP >100 pg/mL or pro-BNP >900 pg/mL 1

Clinical Deterioration After Starting Anticoagulation:

• Decrease in systolic blood pressure (not yet hypotensive)
• Increase in heart rate
• Worsening gas exchange
• Signs of inadequate tissue perfusion
• Worsening right ventricular function
• Increasing cardiac biomarkers 1

Decision Algorithm for Thrombolysis in Submassive PE

1. Confirm diagnosis of PE with appropriate imaging (CT pulmonary angiogram, V/Q scan)
2. Assess hemodynamic status:
   • If hypotensive (systolic BP <90 mmHg): Consider as massive PE → thrombolysis indicated
   • If normotensive: Proceed to next step
3. Evaluate for RV dysfunction:
   • Perform echocardiography to assess RV function
   • Measure cardiac biomarkers (troponin, BNP)
4. Assess bleeding risk:
   • Review absolute and relative contraindications to thrombolysis
   • Consider age (patients >75 years have higher bleeding risk) 2
5. Monitor for clinical deterioration after starting anticoagulation
6. Consider thrombolysis if:
   • RV dysfunction present AND
   • Low bleeding risk AND
   • Either:
     • Signs of clinical deterioration OR
     • Severe RV dysfunction with elevated biomarkers

Important Considerations and Caveats

• The benefit of thrombolysis in submassive PE remains controversial, with benefits and risks finely balanced 1
• Mortality in submassive PE with modern anticoagulation is less than 5% 1
• Major bleeding risk is significantly increased with thrombolysis (65 more events per 1,000 cases) 1
• Patients over 75 years of age have particularly high bleeding risk with full-dose thrombolysis 2
• Consider reduced-dose thrombolysis or catheter-directed therapies in patients with high bleeding risk 2
• Thrombolysis is not recommended in patients with only one risk marker (either RV dilation alone or elevated cardiac biomarker alone) 2

Administration of Thrombolysis

If thrombolysis is indicated:

• Administer via peripheral intravenous catheter
• Standard dose: Alteplase 100 mg over 2 hours IV 1
• Consider withholding anticoagulation during the 2-hour infusion period
• Resume anticoagulation after completion of thrombolysis

Alternative Approaches

For patients with contraindications to systemic thrombolysis or high bleeding risk:

• Consider catheter-directed thrombolysis (lower dose of thrombolytic)
• Consider surgical embolectomy in patients with contraindications to thrombolysis or failed thrombolysis 1

Remember that the decision to administer thrombolysis in submassive PE requires careful assessment of the risk-benefit ratio for each individual patient, with particular attention to bleeding risk and severity of RV dysfunction.