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

Alteplase Dosing for 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, 2, 3

This is the FDA-approved regimen and represents the standard of care endorsed by the American Heart Association and American College of Cardiology. 1, 2

Clinical Context and Definitions

Massive PE Criteria

Massive PE is defined by hemodynamic compromise including: 1, 2

• Sustained hypotension (systolic blood pressure <90 mm Hg for ≥15 minutes)
• Shock index >1.0
• Respiratory failure (SaO2 <95% with respiratory distress or altered mental status)
• Evidence of moderate to severe right ventricular dysfunction on echocardiography or elevated cardiac biomarkers (troponin, BNP >100 pg/mL, or pro-BNP >900 pg/mL) 1

Dosing Protocols by Clinical Scenario

Standard Protocol (Most Common)

• Alteplase 100 mg IV infusion over 2 hours 1, 2, 3
• Withhold anticoagulation during the 2-hour infusion period per FDA recommendation 1, 2
• Resume heparin anticoagulation after completion of alteplase infusion 2

Alternative Accelerated Regimen

For hemodynamically stable patients with confirmed massive PE: 2, 3

• Alteplase 100 mg over 90 minutes (accelerated myocardial infarction regimen)

Emergency Bolus Regimen

For cardiac arrest or rapidly deteriorating condition: 2, 3

• Alteplase 50 mg as IV bolus
• This regimen showed efficacy in a study using 0.6 mg/kg bolus over 15 minutes with 23.8% mortality 4

Weight-Based Considerations

Fixed-dose alteplase (100 mg) may lead to variable drug exposure based on patient weight, which correlates with bleeding risk and coagulopathy. 5

• Doses >50 mg are associated with 6.5-fold increased odds of post-thrombolytic coagulopathy 5
• Dose normalized to actual body weight and estimated blood volume correlates with fibrinogen depletion and INR elevation 5
• Patients with lower body weight have higher risk of bleeding complications 6

Pediatric Dosing

For pediatric patients with PE, weight-based dosing is used: 1

• Standard systemic thrombolysis: 0.5 mg/kg/hour over 6 hours (range 0.1-0.5 mg/kg/hour over 2-6 hours)
• Low-dose regimen: 0.01-0.06 mg/kg/hour for 12-48 hours
• Neonates may require higher doses at 0.06 mg/kg/hour with fresh frozen plasma supplementation due to low plasminogen levels 1
• Maximum total dose: 100 mg 3

Catheter-Directed Thrombolysis

For catheter-directed therapy (CDT) as an alternative to systemic thrombolysis: 1, 7

• Adult dosing: 0.5-1 mg/hour via catheter
• Pediatric dosing: 0.01-0.03 mg/kg/hour (maximum 2 mg/hour)
• Ultra-low-dose protocol: 10 mg total over 5 hours (1 mg/hour/catheter bilaterally) showed significant hemodynamic improvement with minimal bleeding risk 7

Critical Safety Considerations

Bleeding Risk Factors

Patients with the following have significantly increased bleeding risk: 6

• Recent major surgery (9-fold increased odds) 6
• INR >1.7 (13-fold increased odds) 6
• One or more bleeding risk factors (5-fold increased odds) 6
• Lower body weight (18% increased odds for each 10 kg below 100 kg) 6

Post-Thrombolytic Coagulopathy

• Occurs in 35.3% of patients receiving alteplase for PE 5
• Defined as INR >1.5 (21.8% incidence) or fibrinogen <170 mg/dL (26% incidence) 5
• Patients with post-thrombolytic coagulopathy have higher bleeding rates (58.3% vs 28.6%) 5

Major Bleeding Incidence

• Overall major bleeding occurs in 10-40% of patients treated with thrombolytics 1, 3
• No intracranial hemorrhage or stroke occurred in comparative studies of standard dosing 8

Clinical Decision Algorithm

Step 1: Confirm Massive PE

• Imaging confirmation preferred, but may proceed with high clinical suspicion and RV dysfunction on bedside echocardiography if patient too unstable for imaging 1, 2, 3

Step 2: Assess Contraindications

Absolute contraindications: 3

• Active bleeding
• Recent stroke
• Current GI hemorrhage

Relative contraindications: 3

• Recent surgery within 7 days
• Peptic ulcer disease
• Prolonged CPR

Step 3: Select Dosing Regimen

• Hemodynamically unstable but not in arrest: 100 mg over 2 hours 1, 2, 3
• Cardiac arrest/extreme instability: 50 mg bolus 2, 3
• Contraindication to systemic therapy: Consider catheter-directed therapy at 0.5-1 mg/hour 1, 7

Step 4: Anticoagulation Management

• Hold heparin during 2-hour alteplase infusion 1, 2
• Resume therapeutic anticoagulation after completion 2
• For catheter-directed therapy, low-dose UFH (5-10 U/kg/hour) may be used concurrently 1

Common Pitfalls to Avoid

• Do not use the stroke dosing protocol (0.9 mg/kg with 10% bolus) for PE - this is a different indication requiring different dosing 3
• Do not aggressively volume load patients - this worsens RV function through mechanical overstretch 9
• Do not delay treatment for imaging in unstable patients - proceed based on clinical suspicion and bedside echo findings 1, 2
• Do not ignore bleeding risk factors - carefully weigh risks versus benefits, as presence of risk factors increases bleeding odds 5-fold 6