Reteplase for Pulmonary Embolism Thrombolysis
Reteplase is not included in current major international guidelines for pulmonary embolism treatment, and rtPA (alteplase) or tenecteplase remain the guideline-recommended thrombolytic agents. 1
Guideline-Recommended Thrombolytic Agents
The 2019 ESC Guidelines for acute pulmonary embolism specify only three thrombolytic regimens 1:
- rtPA (alteplase): 100 mg over 2 hours, or 0.6 mg/kg over 15 minutes (maximum 50 mg) for extreme hemodynamic instability 1
- Streptokinase: 250,000 IU loading dose over 30 minutes, followed by 100,000 IU/h over 12-24 hours (or accelerated: 1.5 million IU over 2 hours) 1
- Urokinase: 4,400 IU/kg loading dose over 10 minutes, followed by 4,400 IU/kg/h over 12-24 hours (or accelerated: 3 million IU over 2 hours) 1
Tenecteplase is also recommended using weight-based dosing (30-50 mg based on body weight as a single IV bolus over 5 seconds), particularly for high-risk PE with hemodynamic instability 2.
Reteplase Data in Pulmonary Embolism
While reteplase is not guideline-approved for PE, limited research data exists:
Dosing Regimen from Research Studies
- Double bolus regimen: Two 10 U bolus injections given 30 minutes apart (total 20 U) 3, 4, 5
- Each bolus administered over 2 minutes 4, 5
- Administered with concurrent intravenous heparin 3
Efficacy Evidence
A randomized trial of 36 patients with massive PE compared reteplase (n=23) versus alteplase (n=13) and found 3:
- Reteplase showed significant decrease in total pulmonary resistance at 0.5 hours (faster than alteplase at 2 hours) 3
- No significant difference in hemodynamic parameters between agents at 24 hours 3
- No strokes or intracranial hemorrhages occurred 3
- Bleeding rates were comparable between agents 3
Mechanism Advantages
Reteplase has structural differences from alteplase that theoretically improve thrombolysis 1:
- Lacks several structural domains of alteplase, allowing improved penetration into thrombus 1
- Enables fibrinolysis throughout the thrombus rather than just at the surface 1
- Longer half-life permits bolus administration rather than prolonged infusion 4, 5
Critical Clinical Recommendation
Use guideline-recommended agents (alteplase or tenecteplase) for PE thrombolysis rather than reteplase. 1, 2
Why Alteplase or Tenecteplase Should Be Preferred
- Alteplase has extensive validation in large PE trials and is the most established thrombolytic for PE 1
- Tenecteplase has been studied in the landmark PEITHO trial (1,006 patients) with established efficacy and safety profiles 2
- Both agents have defined contraindications, monitoring protocols, and outcome data in PE populations 1, 2
- Reteplase data in PE consists of only one small randomized trial (36 patients) and case reports 3, 6
If Reteplase Were to Be Used (Off-Guideline)
Based on the limited available evidence, the regimen would be 3, 4, 5:
- 20 U total dose: 10 U IV bolus over 2 minutes, followed by second 10 U IV bolus over 2 minutes, 30 minutes after the first bolus 3, 4, 5
- Administer with concurrent heparin infusion 3
- Non-weight-based dosing (unlike alteplase or tenecteplase) 4, 5
Contraindications to Thrombolysis
Absolute contraindications apply regardless of agent 1:
- History of hemorrhagic stroke or stroke of unknown origin 1
- Ischemic stroke in previous 6 months 1
- Central nervous system neoplasm 1
- Major trauma, surgery, or head injury in previous 3 weeks 1
- Bleeding diathesis or active bleeding 1
Common Pitfalls
- Do not use reteplase as first-line therapy when guideline-recommended agents are available 1
- Do not assume reteplase dosing from MI protocols applies to PE—the PE regimen (20 U total) differs from STEMI dosing 3, 4
- Do not delay thrombolysis in high-risk PE while searching for alternative agents—use what is immediately available and guideline-supported 1
- Do not use thrombolytics in intermediate-risk PE without careful risk-benefit assessment, as bleeding risk (particularly intracranial hemorrhage at 1.7-2%) may outweigh benefits 1, 2