What is the recommended dose of thrombolytics (tissue plasminogen activators, tPA), such as alteplase (tPA), tenecteplase (TNK-tPA), and streptokinase, for the management of myocardial infarction?

Thrombolytic Dosing for Myocardial Infarction

For ST-elevation myocardial infarction (STEMI), use tenecteplase as a single weight-based IV bolus (30-50 mg based on body weight) or alteplase 100 mg over 90 minutes (accelerated regimen), with fibrin-specific agents strongly preferred over streptokinase. 1

Recommended Thrombolytic Agents and Doses

First-Line: Fibrin-Specific Agents

Tenecteplase (TNK-tPA) - Preferred for ease of administration 1:

• Single IV bolus over 5 seconds 2
• Weight-based dosing 1:
  • <60 kg: 30 mg
  • 60 to <70 kg: 35 mg
  • 70 to <80 kg: 40 mg
  • 80 to <90 kg: 45 mg
  • ≥90 kg: 50 mg

Alteplase (tPA) - Accelerated regimen 1:

• Total dose: 100 mg over 90 minutes (maximum, weight-adjusted) 1
• 15 mg IV bolus over 1-2 minutes 1
• 0.75 mg/kg over 30 minutes (up to 50 mg) 1
• 0.5 mg/kg over 60 minutes (up to 35 mg) 1

Reteplase (r-PA) 1:

• 10 units IV bolus 1
• Followed by second 10 units IV bolus 30 minutes later 1

Second-Line: Non-Fibrin-Specific Agent

Streptokinase - Only if fibrin-specific agents unavailable 1:

• 1.5 million units IV over 30-60 minutes 1
• Contraindicated if prior streptokinase or anistreplase use (antibodies persist ≥10 years) 1

Critical Timing Considerations

• Initiate within 12 hours of symptom onset for maximum benefit 1, 3
• Greatest mortality reduction when given within first 2 hours 1
• Consider fibrinolysis if primary PCI cannot be performed within 120 minutes of first medical contact 1
• For patients presenting <2 hours with large infarct and low bleeding risk, consider fibrinolysis if PCI delayed >90 minutes 1

Mandatory Adjunctive Therapy

Antiplatelet agents 1:

• Aspirin 150-325 mg orally (chewed, non-enteric coated) or 250 mg IV if unable to take orally 1
• Clopidogrel 300-600 mg loading dose 1

Anticoagulation - Required with all thrombolytics 1:

• With tenecteplase or alteplase: Unfractionated heparin (60 U/kg IV bolus, max 4000 U, then 12 U/kg/h infusion, max 1000 U/h, target aPTT 50-70 seconds) for 24-48 hours 1
• Alternative with tenecteplase/alteplase: Enoxaparin IV bolus followed by subcutaneous dosing (preferred over UFH) 1
• With streptokinase: Fondaparinux IV bolus followed by subcutaneous dose 24 hours later 1

Comparative Efficacy Data

The accelerated alteplase regimen and tenecteplase achieve superior outcomes compared to streptokinase 1:

• TIMI grade 3 flow rates: Tenecteplase/alteplase 54-60% vs. streptokinase 32% 1
• 90-minute patency: Tenecteplase/alteplase ~75% vs. streptokinase ~50% 1
• 30-day mortality: Similar between fibrin-specific agents (7.2-7.5%) 1

Tenecteplase offers practical advantages over alteplase with similar efficacy 4:

• Single bolus administration vs. 90-minute infusion 4
• Slightly lower major bleeding rates (though intracranial hemorrhage rates equivalent) 4
• No difference in 30-day mortality or stroke rates 4

Critical Contraindications

Absolute contraindications 3, 5:

• Any prior intracranial hemorrhage 3, 5
• Active internal bleeding 3, 5, 6, 2
• Known intracranial neoplasm or arteriovenous malformation 3, 5
• Ischemic stroke within 3 months 3, 5
• Suspected aortic dissection 3, 5
• Significant closed-head or facial trauma within 3 months 3

Relative contraindications requiring careful risk-benefit assessment 3, 5:

• Severe uncontrolled hypertension (SBP >180 mmHg or DBP >110 mmHg) 3, 5
• Traumatic or prolonged CPR (>10 minutes) 3, 5
• Major surgery within 3 weeks 3, 5
• Active peptic ulcer disease 3, 5
• Pregnancy 3, 5
• Current oral anticoagulation 3, 5

Common Pitfalls to Avoid

• Do not confuse stroke and MI dosing: Alteplase for stroke is 0.9 mg/kg (max 90 mg), NOT the 100 mg MI dose 1
• Do not add other medications to infusion lines containing alteplase 6
• Do not use streptokinase if patient received it previously (even years ago) 1
• Diabetes and diabetic retinopathy are NOT contraindications to fibrinolytic therapy 5
• Successful brief resuscitation is NOT a contraindication, but prolonged/traumatic CPR >10 minutes is a relative contraindication 5

Post-Thrombolysis Management

• Transfer all patients to PCI-capable center after fibrinolysis 1
• Rescue PCI indicated immediately if <50% ST-segment resolution at 60 minutes 1
• Routine angiography recommended 3-24 hours after successful fibrinolysis in stable patients 1
• Monitor for bleeding complications, particularly intracranial hemorrhage (risk ~1%) 1, 7