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

Alteplase Dosing for Acute Pulmonary Embolism

Standard Dose Recommendation

For massive pulmonary embolism with hemodynamic instability, administer alteplase 100 mg as a continuous intravenous infusion over 2 hours via a peripheral intravenous catheter. 1

This is the FDA-approved dose endorsed by the American Heart Association and American College of Cardiology for patients presenting with sustained hypotension (systolic blood pressure <90 mmHg for at least 15 minutes), shock, or pulselessness. 1, 2

Dosing Algorithm by Clinical Presentation

Hemodynamically Unstable (Massive PE)

• Standard regimen: 100 mg alteplase over 2 hours (10 mg bolus followed by 90 mg infusion) 1, 3
• Alternative accelerated regimen: 100 mg over 90 minutes for hemodynamically stable patients with confirmed massive PE 1

Cardiac Arrest or Rapidly Deteriorating

• Emergency bolus: 50 mg alteplase as immediate IV bolus 1, 2
• Reassess at 30 minutes and consider additional dosing 1
• This approach is supported by the British Thoracic Society for life-threatening presentations where the high mortality without treatment justifies ignoring most relative contraindications 1

Submassive PE (RV Dysfunction Without Hypotension)

• Thrombolysis may be considered but is not routinely recommended 2
• The mortality benefit is established specifically for massive PE with hemodynamic compromise, not for hemodynamically stable patients 1

Anticoagulation Management

Critical timing considerations:

• Withhold heparin during the entire 2-hour alteplase infusion 1, 2
• Resume unfractionated heparin 3 hours after completion of the alteplase infusion using weight-adjusted dosing (typically 1280 IU/hour continuous infusion) 1, 2
• Only resume when APTT is less than twice the upper limit of normal 2

Diagnostic Confirmation

Imaging confirmation is strongly preferred before initiating thrombolysis (CTPA or V/Q scan), but when the patient is too unstable for transport or imaging: 1, 2

• Proceed based on high clinical suspicion combined with bedside echocardiography showing RV dysfunction 1, 2
• This is particularly relevant when sustained hypotension, unexplained hypoxia, engorged neck veins, and right ventricular gallop are present together 4

Evidence Quality and Comparative Data

The 100 mg over 2-hour regimen is supported by multiple randomized trials demonstrating:

• Significant decrease in total pulmonary resistance within 2 hours 3, 5
• Mean pulmonary artery pressure reduction from 30.2 ± 7.8 mm Hg to 21.4 ± 6.7 mm Hg 3
• Faster hemodynamic improvement compared to heparin alone (Miller index decreased from 28.3 ± 2.9 to 24.8 ± 5.2 at 2 hours) 3

Alternative thrombolytics show similar efficacy: reteplase (10 U + 10 U double bolus) and streptokinase (1.5 million IU over 2 hours) achieve comparable hemodynamic outcomes, though alteplase remains the standard 6, 5

Bleeding Risk and Safety

Prepare for bleeding complications, which occur in 10-40% of patients: 1

• Major bleeding occurred in 15% of patients in controlled trials 3
• Minor bleeding is common (70% in some series) but typically manageable 3, 7
• Intracranial hemorrhage risk exists but is rare when patients are appropriately selected 6, 3

Common Pitfalls to Avoid

• Do not use reduced-dose bolus regimens (such as 0.6 mg/kg over 15 minutes): while studied, these showed no reduction in bleeding complications and potentially higher mortality compared to the standard 100 mg dose 8, 7
• Do not continue heparin during the alteplase infusion: this increases bleeding risk without improving efficacy 1, 2
• Do not delay treatment for imaging in deteriorating patients with high clinical suspicion and bedside echo evidence of RV dysfunction 1
• Do not use thrombolysis routinely in submassive PE without hemodynamic compromise, as mortality benefit has not been demonstrated in this population 1

Special Populations

Catheter-Directed Thrombolysis (Alternative Approach)

• Adult dosing: 0.5-1 mg/hour via catheter 1
• May use concurrent low-dose UFH (5-10 U/kg/hour) 1
• Consider when systemic thrombolysis contraindications exist but patient requires intervention

Pregnancy

• Thrombolysis may be appropriate for massive PE in pregnancy 2
• Avoid within 6 hours of delivery or early postpartum period due to prohibitive bleeding risk 2