What is the recommended dose of alteplase (tissue plasminogen activator) for pulmonary embolism?

Recommended Alteplase Dosing for Pulmonary Embolism

The FDA-recommended dose of alteplase for pulmonary embolism is 100 mg administered as a continuous intravenous infusion over 2 hours. 1

Dosing Based on Clinical Presentation

Massive PE with Hemodynamic Instability

• For patients with confirmed massive PE who are hemodynamically stable, administer 100 mg alteplase over 90 minutes (accelerated myocardial infarction regimen) 2
• For patients with cardiac arrest or rapidly deteriorating condition due to massive PE, administer 50 mg alteplase as an IV bolus 2, 3
• In life-threatening situations where the patient remains unstable after initial bolus, a second 50 mg bolus may be considered based on bedside echocardiographic findings showing persistent right ventricular dysfunction 3
• Anticoagulation with heparin should be withheld during the alteplase infusion period 1
• Resume anticoagulation with unfractionated heparin approximately 3 hours after completing thrombolysis 2, 1

Intermediate-High Risk PE

• For intermediate-high risk PE, ultrasound-assisted catheter-directed thrombolysis (USAT) with lower doses of alteplase (10-20 mg) administered over 5-24 hours has shown efficacy in improving pulmonary hemodynamics with potentially lower bleeding risk 4
• Studies have demonstrated that even very low-dose regimens (10 mg over 5 hours) can improve pulmonary artery pressures and cardiac index 4

Administration Considerations

• Administer alteplase via a peripheral intravenous catheter 1
• The stability of alteplase solutions may be affected by ultrasound exposure during catheter-directed thrombolysis, with approximately 10% degradation every 2 hours when exposed to ultrasound 5
• In patients with massive PE presenting with shock, a more rapid administration (0.6 mg/kg over 15 minutes) has shown efficacy in improving hemodynamics 6

Monitoring and Safety

• Be prepared to manage potential bleeding complications, which occur in 10-40% of patients receiving thrombolytic therapy 1
• Closely monitor hemodynamic parameters, including pulmonary artery pressure and cardiac index, before and after thrombolysis 7, 4
• In life-threatening PE, contraindications to thrombolysis may need to be reconsidered given the high mortality rate without treatment 1

Clinical Decision-Making Algorithm

1. Confirm diagnosis of PE when possible (CT pulmonary angiography, V/Q scan, or bedside echocardiography in unstable patients) 1
2. Assess hemodynamic status and risk stratification:
   • Massive PE (hypotension, shock): 100 mg alteplase over 2 hours, or 50 mg bolus in cardiac arrest/rapidly deteriorating patients 2, 1
   • Intermediate-high risk PE (normotensive with RV dysfunction): Consider standard dose or catheter-directed low-dose approach 4
3. Monitor response to therapy with serial assessment of vital signs and, when possible, follow-up echocardiography 7, 6

Pitfalls and Caveats

• Avoid using alteplase as a routine "screening" treatment without reasonable suspicion of PE 2
• While confirming PE diagnosis before thrombolysis is preferable, in unstable patients with high clinical suspicion and evidence of RV dysfunction, treatment may need to be initiated without definitive imaging 1
• The mortality rate remains high for patients with PE-related cardiac arrest despite thrombolytic therapy, particularly in out-of-hospital arrests 2, 3
• Alternative thrombolytic agents like reteplase (administered as two 10U boluses 30 minutes apart) may provide similar hemodynamic improvements compared to the standard alteplase regimen 7