What is the recommendation for thrombolysis in patients with acute pulmonary embolism?

Thrombolytic Therapy for Acute Pulmonary Embolism

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

Risk Stratification and Treatment Algorithm

High-Risk PE (Massive PE)

• Definition: PE with shock and/or hypotension (systolic BP <90 mmHg or a pressure drop of 40 mmHg for >15 min) 2
• Recommendation: Immediate thrombolysis unless absolute contraindications exist 1, 2
• In life-threatening high-risk PE, contraindications that are normally absolute may be considered relative 1, 2

Intermediate-Risk PE (Submassive PE)

• Definition: Normotensive patients with right ventricular dysfunction (RVD) and/or myocardial injury 1
• Recommendation: Routine thrombolysis is not recommended, but may be considered in selected patients after careful assessment of bleeding risk 1
• Consider thrombolysis if clinical deterioration occurs despite anticoagulation 1

Low-Risk PE

• Recommendation: Thrombolytic therapy should not be used 1
• Standard anticoagulation is sufficient 1

Approved Thrombolytic Regimens

Recombinant Tissue Plasminogen Activator (rtPA/Alteplase)

• Standard regimen: 100 mg over 2 hours 1, 3
• Accelerated regimen: 0.6 mg/kg over 15 minutes (maximum dose 50 mg) 1
• Administration: Via peripheral vein 2, 3

Streptokinase

• Standard regimen: 250,000 IU as loading dose over 30 minutes, followed by 100,000 IU/h over 12-24 hours 1
• Accelerated regimen: 1.5 million IU over 2 hours 1

Urokinase

• Standard regimen: 4,400 IU/kg as loading dose over 10 minutes, followed by 4,400 IU/kg/h over 12-24 hours 1
• Accelerated regimen: 3 million IU over 2 hours 1, 4

Tenecteplase

• Weight-based dosing:
  • <60 kg: 30 mg
  • 60-69 kg: 35 mg
  • 70-79 kg: 40 mg
  • 80-89 kg: 45 mg
  • ≥90 kg: 50 mg 2

Contraindications to Thrombolytic Therapy

Absolute Contraindications

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

Relative Contraindications

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

Clinical Benefits and Risks

Benefits

• Rapid improvement in hemodynamics and right ventricular function 5
• Approximately 92% of patients respond to thrombolysis with clinical and echocardiographic improvement within 36 hours 1
• Greatest benefit when initiated within 48 hours of symptom onset, but can be useful up to 6-14 days 1
• Significant reduction in pulmonary artery systolic pressure and improvement in right ventricle/left ventricle ratio 6

Risks

• Major bleeding rate: approximately 13% 1
• Intracranial/fatal hemorrhage rate: approximately 1.8% 1
• Increased risk with age and comorbidities 1

Alternative Approaches

Low-Dose Thrombolysis

• May be considered for intermediate-risk PE to reduce bleeding risk 6
• Shows improved right ventricular function with potentially fewer bleeding complications 6

Ultrasound-Assisted Catheter-Directed Thrombolysis

• Effective in reversing right ventricular dysfunction compared to anticoagulation alone 7
• May be considered for patients with high bleeding risk who require thrombolysis 7

Surgical Pulmonary Embolectomy

• Consider when:
  • Thrombolysis fails or patient deteriorates despite thrombolysis
  • Absolute contraindications to thrombolysis exist
  • Patient has patent foramen ovale with intracardiac thrombi 1
• Requires centers with routine cardiac surgery programs 1

Key Clinical Pitfalls and Caveats

• Avoid delay in administering thrombolysis for high-risk PE; mortality benefit outweighs bleeding risk
• Contraindications to thrombolysis may become relative in immediately life-threatening high-risk PE 1, 2
• The hemodynamic benefits of thrombolysis over heparin appear to be confined to the first few days 1
• Monitor patients closely for bleeding complications during and after thrombolysis
• Consider patient age and comorbidities when assessing bleeding risk
• Avoid diuretics and vasodilators in patients with massive or submassive PE 2

In conclusion, thrombolytic therapy remains a cornerstone in the management of high-risk PE, with potential benefits in selected intermediate-risk patients. The decision to use thrombolysis must balance the potential mortality benefit against bleeding risk, with risk stratification guiding treatment selection.