What is the recommended dose of fibrinolytic therapy, such as tenecteplase (TNK-tPA), alteplase (t-PA), or reteplase (r-PA), for a patient presenting with ST-Elevation Myocardial Infarction (STEMI)?

Fibrinolytic Therapy Dosing for STEMI

For STEMI patients requiring fibrinolytic therapy, tenecteplase is the preferred agent administered as a single weight-based IV bolus: 30 mg for <60 kg, 35 mg for 60-69 kg, 40 mg for 70-79 kg, 45 mg for 80-89 kg, and 50 mg for ≥90 kg, given over 5 seconds. 1, 2

Weight-Based Dosing for Tenecteplase (TNK-tPA)

Tenecteplase offers the most convenient administration as a single bolus, making it ideal for rapid treatment initiation 1:

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

The bolus is administered over 5 seconds via direct IV push 2. Tenecteplase demonstrates equivalent 30-day mortality to alteplase with reduced non-cerebral bleeding complications 1.

Alternative Fibrinolytic Agents

Reteplase (r-PA)

• Dose: Two 10-unit IV boluses, each given over 2 minutes, separated by 30 minutes 1
• Non-weight-based dosing simplifies administration but requires two separate boluses 1

Alteplase (t-PA)

For patients ≥67 kg 1:

• 15 mg IV bolus initially
• 50 mg IV infused over 30 minutes
• 35 mg IV infused over next 60 minutes
• Total dose: 100 mg over 90 minutes 1

For patients <67 kg 1:

• 15 mg IV bolus initially
• 0.75 mg/kg IV (maximum 50 mg) over 30 minutes
• 0.5 mg/kg IV (maximum 35 mg) over next 60 minutes
• Total maximum dose: 100 mg 1

Critical Timing Considerations

Fibrinolytic therapy is indicated when primary PCI cannot be performed within 120 minutes of first medical contact 1. The greatest mortality benefit occurs when treatment is initiated within 12 hours of symptom onset, with maximal benefit in patients presenting within the first 2 hours 1.

For patients presenting 12-24 hours after symptom onset, fibrinolytic therapy is reasonable only if there is evidence of ongoing ischemia with large myocardium at risk or hemodynamic instability, and PCI remains unavailable 1.

Mandatory Adjunctive Antiplatelet Therapy

All patients receiving fibrinolytics require dual antiplatelet therapy 1:

Aspirin 1:

• Loading dose: 162-325 mg orally (or 80-150 mg IV if unable to take oral)
• Maintenance: 81 mg daily indefinitely

Clopidogrel 1:

• Age <75 years: 300 mg loading dose, then 75 mg daily
• Age ≥75 years: No loading dose; start 75 mg daily
• Continue for minimum 14 days, preferably up to 1 year 1

Required Anticoagulation

Anticoagulation must be administered for minimum 48 hours, preferably until revascularization or hospital discharge (up to 8 days) 1:

Enoxaparin (Preferred) 3, 4

Age <75 years:

• 30 mg IV bolus
• Then 1 mg/kg subcutaneous every 12 hours

Age ≥75 years:

• No IV bolus
• 0.75 mg/kg subcutaneous every 12 hours

Unfractionated Heparin (Alternative) 1, 3

• 60 units/kg IV bolus (maximum 4,000 units)
• 12 units/kg/hour infusion (maximum 1,000 units/hour)
• Target aPTT 1.5-2.0 times control for 48 hours

Absolute Contraindications

Do not administer fibrinolytics if any of the following are present 1, 2:

• Any prior intracranial hemorrhage 1, 2
• Known structural cerebral vascular lesion (arteriovenous malformation) 1, 2
• Known malignant intracranial neoplasm (primary or metastatic) 1, 2
• Ischemic stroke within 3 months 1, 2
• Suspected aortic dissection 1, 2
• Active bleeding or bleeding diathesis (excluding menses) 1, 2
• Significant closed-head or facial trauma within 3 months 1, 2
• Intracranial or intraspinal surgery within 2 months 1, 2
• Severe uncontrolled hypertension (SBP >180 mmHg or DBP >110 mmHg unresponsive to therapy) 1, 2

Critical Administration Details

Reconstitution of tenecteplase 2:

• Use only the supplied 10 mL Sterile Water for Injection
• Final concentration: 5 mg/mL
• Gently swirl; do not shake
• Use immediately or refrigerate at 2-8°C and use within 8 hours

Avoid dextrose-containing IV lines 2: Tenecteplase precipitates with dextrose. Flush lines with 0.9% sodium chloride before and after administration 2.

Post-Fibrinolytic Management

All patients must be transferred to a PCI-capable center following fibrinolysis 3, 5. Routine angiography should occur 2-24 hours after successful fibrinolysis in stable patients 5. Emergency angiography is indicated immediately if fibrinolysis fails, defined as <50% ST-segment resolution at 60-90 minutes 5.

Common Pitfalls to Avoid

Age-related dosing errors: Elderly patients (≥75 years) receiving enoxaparin should not receive the IV bolus and require reduced subcutaneous dosing (0.75 mg/kg vs 1 mg/kg) due to increased intracranial hemorrhage risk 4.

Relative contraindication misinterpretation: Significant hypertension on presentation (SBP >180 or DBP >110 mmHg) is a relative contraindication that can be addressed with emergent blood pressure control before fibrinolytic administration 1. However, if hypertension remains unresponsive to therapy, it becomes an absolute contraindication 1.

ST-depression misuse: Fibrinolytic therapy is contraindicated in isolated ST-depression unless true posterior (inferobasal) MI is suspected or when associated with ST-elevation in lead aVR 1.