What are the recommended doses of streptokinase (Streptokinase), alteplase (tPA - Tissue Plasminogen Activator), and tenecteplase (TNK-tPA - Tissue Plasminogen Activator) for thrombolysis in Myocardial Infarction (MI)?

Thrombolytic Dosing for Myocardial Infarction

For STEMI patients requiring fibrinolysis, tenecteplase is the preferred agent given as a single weight-based IV bolus, with streptokinase 1.5 million units over 30-60 minutes as an alternative when cost is a major consideration, and alteplase reserved for specific situations requiring a titratable infusion. 1, 2

Tenecteplase (TNK-tPA) - Preferred Agent

Weight-based single IV bolus over 5 seconds: 1, 2, 3

• <60 kg: 30 mg (6 mL) 1, 2, 3
• 60-69 kg: 35 mg (7 mL) 1, 2, 3
• 70-79 kg: 40 mg (8 mL) 1, 2, 3
• 80-89 kg: 45 mg (9 mL) 1, 2, 3
• ≥90 kg: 50 mg (10 mL) 1, 2, 3

Advantages: Single bolus administration allows for rapid pre-hospital use, achieves 85% TIMI 2-3 flow at 90 minutes, and has been extensively studied in pharmacoinvasive strategies. 1, 2

Alteplase (tPA) - Alternative Agent

90-minute weight-based infusion: 1

• 15 mg IV bolus 1
• 0.75 mg/kg over 30 minutes (maximum 50 mg) 1
• 0.5 mg/kg over 60 minutes (maximum 35 mg) 1
• Total dose not to exceed 100 mg 1

Advantages: For patients presenting within 6 hours of symptom onset, alteplase demonstrates superior mortality reduction compared to streptokinase (Grade 1A evidence), achieving 73-84% TIMI 2-3 flow at 90 minutes. 1, 4

Streptokinase - Cost-Effective Alternative

1.5 million units IV over 30-60 minutes 1, 5

Critical contraindication: Absolutely contraindicated within 6 months of previous streptokinase or anistreplase exposure due to antibody formation causing serious allergic reactions and impaired efficacy. 1, 5

Advantages: Significantly lower cost, achieves 60-68% TIMI 2-3 flow at 90 minutes, and when combined with aspirin produces 42% mortality reduction. 1, 5

Disadvantages: Lower patency rates than fibrin-specific agents, risk of hypotension during infusion, and cannot be re-administered. 1, 5

Mandatory Adjunctive Antiplatelet Therapy

All patients regardless of fibrinolytic choice: 1, 2, 5

• Aspirin: 150-325 mg loading dose (chewed or IV 80-150 mg if unable to swallow), then 75-100 mg daily indefinitely 1, 2, 5
• Clopidogrel: 300 mg loading dose for patients ≤75 years (75 mg for >75 years), then 75 mg daily for minimum 14 days 1, 2, 5

Do not use prasugrel or ticagrelor as adjuncts to fibrinolysis—they have not been studied in this context and should be avoided. 1

Required Anticoagulation

Duration: Minimum 48 hours, preferably until revascularization or hospital discharge (up to 8 days). 1, 2, 5

With Tenecteplase or Alteplase:

Enoxaparin (preferred over UFH): 1, 2, 3

• Age <75 years: 30 mg IV bolus, then 1 mg/kg SC every 12 hours 1
• Age ≥75 years: No IV bolus, 0.75 mg/kg SC every 12 hours 1
• Renal dysfunction (CrCl <30 mL/min): Contraindicated; use UFH instead 1

Unfractionated heparin (alternative): 1

• 60 U/kg IV bolus (maximum 4000 U) 1, 5
• 12 U/kg/hour infusion (maximum 1000 U/hour) 1, 5
• Target aPTT: 50-70 seconds (1.5-2.0 times control), checked at 3,6,12, and 24 hours 1

With Streptokinase:

Fondaparinux (preferred): 1, 5

• 2.5 mg IV bolus, then 2.5 mg SC once daily 1, 5
• Superior to UFH with streptokinase in reducing death and reinfarction 1, 5

Enoxaparin or UFH (alternatives): Same dosing as above 1, 5

Timing Considerations

Fibrinolysis is indicated when primary PCI cannot be performed within 120 minutes of first medical contact. 1, 2, 3

For patients presenting <2 hours with large infarct and low bleeding risk, consider fibrinolysis if PCI delay >90 minutes. 1, 2

Pre-hospital administration is strongly preferred when feasible—aim for treatment within 30 minutes of first medical contact. 1, 2

Greatest benefit occurs within first 6 hours; treatment remains beneficial up to 12 hours after symptom onset. 1, 4

Post-Fibrinolysis Management

Monitor for successful reperfusion at 60-90 minutes: 2, 3

• Relief of chest pain 2
• Hemodynamic/electrical stability 2
• ≥50% reduction in ST-segment elevation 2, 3

Transfer all patients to PCI-capable center following fibrinolysis. 1, 2, 5, 3

Angiography timing: 1, 2, 3

• Successful fibrinolysis: 3-24 hours (optimal timing) 1, 2, 3
• Failed fibrinolysis (<50% ST resolution): Emergency rescue PCI immediately 1, 2, 3
• Hemodynamic instability/cardiogenic shock: Emergency angiography 1

Critical Safety Considerations

Absolute contraindications (all agents): 1

• Any prior intracranial hemorrhage 1
• Ischemic stroke within 3 months 1
• Known intracranial vascular malformation or neoplasm 1
• Active bleeding or bleeding diathesis 1
• Suspected aortic dissection 1
• Significant closed head/facial trauma within 3 months 1
• Intracranial/intraspinal surgery within 2 months 1
• Severe uncontrolled hypertension (SBP >180 or DBP >110 mmHg unresponsive to emergency therapy) 1

Intracranial hemorrhage risk: 0.9-1.0% overall, increased with lower weight, female sex, previous cerebrovascular disease, and hypertension on admission. 1, 5

Common pitfall: Avoid enoxaparin in patients >75 years receiving tenecteplase due to increased intracranial hemorrhage risk demonstrated in ASSENT-3 PLUS trial; use reduced dose (0.75 mg/kg SC without bolus) or switch to UFH. 1, 2