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

Alteplase Dosing for Pulmonary Thromboembolism

The recommended dose of alteplase for pulmonary thromboembolism is 100 mg IV infused over 2 hours, which is the FDA-approved standard dosing regimen for adults. 1, 2

Standard Dosing Protocol

• Standard adult dose: 100 mg IV infused over 2 hours 1, 2
• For severe cases requiring accelerated administration: 0.6 mg/kg IV over 15 minutes (maximum 50 mg) 2

Clinical Considerations

Indications for Thrombolytic Therapy

• First-line treatment for patients with cardiogenic shock due to pulmonary embolism 2
• Consider in hemodynamically unstable patients with massive PE

Concomitant Anticoagulation

• Initial anticoagulation with unfractionated heparin (UFH) is recommended:
  • 80 units/kg IV bolus followed by 18 U/kg/h continuous infusion 2
  • Target aPTT: 1.5-2.5 times control value (46-70 seconds) 2
• Low-dose UFH (5-10 U/kg per hour) is commonly used with thrombolysis 1
• LMWH is generally not recommended with thrombolysis due to its longer half-life and less reversibility compared to UFH 1

Risk Factors for Bleeding Complications

Major bleeding occurs in approximately 13% of patients, with intracranial/fatal hemorrhage in about 1.8% 2. Risk factors include:

• Recent major surgery (OR 9.00) 3
• INR above 1.7 (OR 13.20) 3
• Lower body weight (increased risk for each 10 kg below 100 kg) 3
• Advanced age 2
• Multiple comorbidities 2

Management of Bleeding Complications

For bleeding complications, consider:

• Tranexamic acid or aminocaproic acid 1, 2
• Fresh frozen plasma or cryoprecipitate, especially in cases of hypofibrinogenemia 1, 2
• Monitor fibrinogen levels during thrombolysis (maintain >1.0 g/L) 2

Alternative Thrombolytic Regimens

While the standard 100 mg over 2 hours is recommended, alternative regimens have been studied:

• Reteplase: 10 U + 10 U as two IV bolus injections 30 minutes apart 4
• Tenecteplase: Weight-based IV bolus (30-50 mg based on weight) 2
• Streptokinase: 250,000 IU over 20-30 minutes followed by 100,000 IU/hour IV for up to 24 hours 2

Important Caveats

1. Absolute contraindications to thrombolysis include hemorrhagic stroke, recent major trauma/surgery, and active bleeding 2

2. Relative contraindications include transient ischemic attack in preceding 6 months, oral anticoagulant therapy, and pregnancy 2

3. The presence of one or more risk factors for bleeding increases the odds of major bleeding by approximately 5 times 3

4. While accelerated regimens (0.6 mg/kg over 15 minutes) have shown efficacy in some studies 5, the standard 100 mg over 2 hours remains the FDA-approved dosing

5. Surgical pulmonary embolectomy should be considered when thrombolysis is absolutely contraindicated or has failed 2

The evidence consistently supports the standard 100 mg over 2 hours as the recommended dose for pulmonary thromboembolism, with specific alternative regimens available for particular clinical scenarios.