What are the systemic thrombolytics and heparin dosing regimens for thromboembolism?

Systemic Thrombolytics and Heparin Regimens for Thromboembolism

For thromboembolism treatment, systemic thrombolytics should be administered with concurrent low-dose heparin, with specific regimens varying by thrombolytic agent and clinical scenario. 1

Systemic Thrombolytic Agents and Dosing

Alteplase (tPA)

• Standard regimen: 100 mg IV over 2 hours 2, 1
• Accelerated regimen: 0.6 mg/kg IV over 15 minutes (maximum 50 mg) - for severe cases 2, 1
• Low-dose regimen for pediatrics: 0.01-0.06 mg/kg/hour for 12-48 hours 2

Streptokinase

• Standard regimen: 250,000 IU loading dose over 30 minutes, followed by 100,000 IU/hour over 12-24 hours 2, 1
• Accelerated regimen: 1.5 million IU over 2 hours 2

Urokinase

• Standard regimen: 4,400 IU/kg loading dose over 10 minutes, followed by 4,400 IU/kg/hour over 12-24 hours 2
• Accelerated regimen: 3 million IU over 2 hours 2

Tenecteplase

• Weight-based dosing:
  • <60 kg: 30 mg IV bolus
  • 60-69 kg: 35 mg IV bolus
  • 70-79 kg: 40 mg IV bolus
  • 80-89 kg: 45 mg IV bolus
  • ≥90 kg: 50 mg IV bolus 1

Concurrent Heparin Administration

With Fibrin-Specific Thrombolytics (Alteplase, Reteplase, Tenecteplase)

• Recommended: Concurrent heparin should be administered 2
• Initial bolus: 60 U/kg IV (maximum 4,000 U) 2
• Maintenance infusion: 12 U/kg/hour (maximum 1,000 U/hour) 2
• Target aPTT: 1.5-2.0 times control (50-70 seconds) 2
• Duration: Continue for 48 hours, then consider transitioning based on risk 2

With Non-Fibrin-Specific Thrombolytics (Streptokinase, Urokinase)

• Not routinely recommended within first 6 hours unless high risk for systemic embolism 2
• For high-risk patients (large/anterior MI, atrial fibrillation, previous embolus, known LV thrombus):
  • Withhold heparin for 4 hours after thrombolytic administration 2
  • Start heparin when aPTT returns to <2 times control (approximately 70 seconds) 2
  • Initial infusion rate: approximately 1,000 U/hour 2
  • Target aPTT: 1.5-2.0 times control 2

For Catheter-Directed Thrombolysis

• Low-dose regimen: 2,000 U bolus followed by 500 U/hour for 4 hours 2
• This regimen reduced symptomatic brain hemorrhage rate to 7-10% compared to 27% with conventional heparin dosing 2

Special Considerations

Pediatric Patients

• Initial heparin dose: 75-100 U/kg IV bolus over 10 minutes 2
• Maintenance dose:
  • Infants <2 months: 25-30 U/kg/hour (highest requirements)
  • Children >1 year: 18-20 U/kg/hour 3
• Target aPTT: 60-85 seconds 2
• Low-dose UFH (5-10 U/kg/hour) is commonly used with thrombolysis in pediatrics 2

Bleeding Risk Management

• Major bleeding occurs in approximately 13% of patients receiving thrombolysis 1
• Intracranial/fatal hemorrhage occurs in approximately 1.8% of patients 1
• Monitor fibrinogen levels during thrombolysis; maintain >1.0 g/L 2
• For bleeding complications: consider tranexamic acid, aminocaproic acid, fresh frozen plasma, or cryoprecipitate 2

Clinical Decision Algorithm

1. Assess clinical scenario:

   • High-risk PE (shock/hypotension): Thrombolysis is first-line therapy 2, 1
   • Intermediate-risk PE (RV dysfunction): Consider thrombolysis after careful bleeding risk assessment 1
   • Acute MI with ST elevation: Thrombolysis if PCI unavailable 2

2. Select thrombolytic agent:

   • Alteplase: Preferred for most scenarios due to reduced mortality, PE recurrence, and improved pulmonary artery pressure 4
   • Streptokinase: Alternative when cost is a concern
   • Tenecteplase: Consider for single-bolus administration in emergency situations

3. Determine heparin regimen:

   • For fibrin-specific agents: Start concurrent heparin
   • For non-fibrin-specific agents: Delay heparin unless high embolic risk

4. Monitor therapy:

   • Check aPTT every 4-6 hours during initial therapy 3
   • Monitor for bleeding complications
   • Assess clinical response within 36 hours 1

Pitfalls and Caveats

• Avoid concurrent LMWH with thrombolysis due to longer half-life and less reversibility compared to UFH 2
• Contraindications to thrombolysis may become relative in life-threatening scenarios 1
• The bleeding risk is higher in patients with recent surgery, history of GI/urinary tract bleeding, or thrombocytopenia 1
• Heparin should be continued beyond 48 hours only in patients at high risk for systemic or venous thromboembolism 2
• Avoid invasive procedures during thrombolytic therapy to minimize bleeding risk 2