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

Alteplase Dosing for Pulmonary Embolism

For pulmonary embolism, alteplase (tPA) should be administered at a dose of 100 mg IV over 2 hours in hemodynamically stable patients, or as a 50 mg IV bolus in cases of cardiac arrest or severe deterioration. 1

Dosing Based on PE Severity

Massive PE (Hemodynamically Unstable)

• Definition: Hemodynamic instability, cardiogenic shock, cardiac arrest, persistent hypotension (systolic BP <90 mmHg) requiring vasopressors 1
• Recommended dosing:
  • Standard: 100 mg IV over 2 hours
  • In cardiac arrest/severe deterioration: 50 mg IV bolus 1

Submassive PE (Hemodynamically Stable)

• Definition: Normal systemic blood pressure with evidence of right ventricular dysfunction on imaging and elevated cardiac biomarkers 1
• Primary treatment: Anticoagulation (thrombolytics generally not first-line) 1
• If thrombolysis is indicated due to clinical deterioration:
  • Same dosing as for massive PE: 100 mg IV over 2 hours 1

Administration Considerations

• Begin heparin therapy along with thrombolytic therapy
• For unfractionated heparin (UFH): 70-80 IU/kg IV bolus, followed by continuous infusion at 18 IU/kg/hr 1
• Target aPTT of 1.5-2.5 times control value 1
• Monitor aPTT 4-6 hours after starting treatment and at least daily thereafter 1

Alternative Thrombolytic Options

• Tenecteplase: Can be used as an alternative to alteplase 1
  • Single weight-based IV bolus:
    • <60 kg: 30 mg
    • 60-69 kg: 35 mg
    • 70-79 kg: 40 mg
    • 80-89 kg: 45 mg
    • ≥90 kg: 50 mg

Important Clinical Considerations

Contraindications to Thrombolytic Therapy

• Absolute contraindications: Prior intracranial hemorrhage, known structural intracranial cerebrovascular disease, active internal bleeding, recent stroke, recent major surgery or trauma, known bleeding diathesis 1
• Relative contraindications: Chronic severe hypertension, significant hypertension on presentation, history of prior ischemic stroke >3 months, dementia, major surgery (<3 weeks), recent internal bleeding, noncompressible vascular punctures, pregnancy, active peptic ulcer, oral anticoagulant therapy 1

Monitoring During Treatment

• Close observation of vital signs and oxygen requirements
• Monitor for signs of bleeding
• Serial echocardiography to assess right ventricular function 1
• Maintain right atrial pressure at 15-20 mmHg 1
• Avoid diuretics and vasodilators in patients with massive PE 1

Alternative Approaches

• For patients with contraindications to thrombolysis or failed thrombolysis:
  • Consider catheter-directed interventions (aspiration thrombectomy, thrombus fragmentation, rheolytic thrombectomy) 1
  • Consider surgical embolectomy 1
  • Transfer patients urgently to centers with these capabilities if not available locally 1

Clinical Evidence and Considerations

While some research has explored reduced-dose alteplase regimens (50 mg or 0.6 mg/kg) 2, 3, the most recent guidelines still recommend the standard 100 mg dose over 2 hours for most cases 1. A 2018 study comparing half-dose (50 mg) versus full-dose (100 mg) alteplase found that half-dose was associated with similar mortality and major bleeding rates, but required more treatment escalation 3. This suggests that while lower doses may be safer, they might be less effective.

For patients in cardiac arrest or with severe hemodynamic compromise, the 50 mg bolus approach is recommended to achieve rapid thrombolysis 1.