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

Indications for Thrombolysis in Pulmonary Embolism

Thrombolytic therapy is the first-line treatment for patients with high-risk PE presenting with cardiogenic shock and/or persistent arterial hypotension, with very few absolute contraindications. 1

Risk Stratification for Thrombolysis

High-Risk PE (Strong Indication)

• Patients with PE presenting with:
  • Shock (cardiogenic shock due to PE)
  • Persistent hypotension (systolic BP <90 mmHg or drop ≥40 mmHg for >15 minutes) 1, 2

Intermediate-Risk PE (Consider Thrombolysis)

• Patients who deteriorate after starting anticoagulant therapy but have not yet developed hypotension 1
• Clinical signs of deterioration include:
  • Decrease in systolic BP (though still >90 mmHg)
  • Increase in heart rate
  • Worsening gas exchange
  • Signs of inadequate tissue perfusion
  • Worsening right ventricular function
  • Increasing cardiac biomarkers 1

Low-Risk PE (Thrombolysis Not Indicated)

• Hemodynamically stable patients without evidence of RV dysfunction or myocardial injury 1, 2
• Patients with small pulmonary emboli not affecting pulmonary artery pressure 3

Contraindications to Thrombolysis

Absolute Contraindications

• Hemorrhagic stroke or stroke of unknown origin at any time
• Ischemic stroke in preceding 6 months
• Central nervous system damage or neoplasms
• Recent major trauma/surgery/head injury (within preceding 3 weeks)
• Gastrointestinal bleeding within the last month
• Known active bleeding 1

Relative Contraindications

• Transient ischemic attack in preceding 6 months
• Oral anticoagulant therapy
• Pregnancy or within 1 week post-partum
• Non-compressible punctures
• Traumatic resuscitation
• Refractory hypertension (systolic BP >180 mmHg)
• Advanced liver disease
• Infective endocarditis
• Active peptic ulcer 1

Important: Contraindications considered absolute in other settings (e.g., acute myocardial infarction) might become relative in a patient with immediately life-threatening high-risk PE 1, 4

Approved Thrombolytic Regimens

Agent	Dosage
Alteplase (rtPA)	100 mg over 2 hours or 0.6 mg/kg over 15 min (maximum dose 50 mg)
Streptokinase	250,000 IU loading dose over 30 min, followed by 100,000 IU/h over 12-24h; or accelerated regimen: 1.5 million IU over 2h
Urokinase	4,400 IU/kg loading dose over 10 min, followed by 4,400 IU/kg/h over 12-24h; or accelerated regimen: 3 million IU over 2h [1]

Alternative Interventions When Thrombolysis is Contraindicated

Surgical Embolectomy

• Indicated when thrombolysis is contraindicated or has failed
• Performed via median sternotomy with normothermic cardiopulmonary bypass
• Most effective for patients with subtotal obstruction of the main pulmonary artery or major branches 1, 2

Catheter-Directed Interventions

• Consider when surgical options are unavailable
• Techniques include:
  • Thrombus fragmentation
  • Rheolytic thrombectomy
  • Suction thrombectomy
  • Rotational thrombectomy 2

Clinical Decision-Making Algorithm

1. Assess hemodynamic status:

   • If shock/hypotension present → High-risk PE → Immediate thrombolysis unless absolute contraindications exist
   • If normotensive → Proceed to step 2

2. Evaluate for signs of RV dysfunction and myocardial injury:

   • Echocardiography showing RV dysfunction
   • Elevated cardiac biomarkers (troponin, BNP)
   • CT evidence of RV enlargement

3. Monitor for clinical deterioration in intermediate-risk patients:

   • If deterioration occurs → Consider thrombolysis if bleeding risk acceptable
   • If stable → Continue anticoagulation alone

4. If thrombolysis contraindicated or failed:

   • Consider surgical embolectomy if available
   • Consider catheter-directed interventions if surgery unavailable

Important Clinical Considerations

• The risk/benefit ratio of thrombolysis is most favorable in high-risk PE patients 1
• Single markers of RV dysfunction or myocardial injury have insufficient positive predictive value for PE-specific mortality to drive decision-making toward thrombolysis in normotensive patients 5
• Thrombolysis in intermediate-risk PE remains controversial but may be considered on a case-by-case basis 6
• The benefit of thrombolysis in reducing mortality has been demonstrated primarily in high-risk PE patients 1
• Major bleeding, including intracranial hemorrhage, is the primary risk of thrombolytic therapy (65 more events per 1,000 cases compared to anticoagulation alone) 1

By following this evidence-based approach to thrombolysis in PE, clinicians can optimize outcomes while minimizing risks in this potentially life-threatening condition.