Indications for Tenecteplase (TNK) Administration Beyond 12 Hours in Myocardial Infarction
Tenecteplase (TNK) should only be administered beyond 12 hours after symptom onset in STEMI patients with ongoing ischemia, a large area of myocardium at risk, or hemodynamic instability when timely primary PCI is not available. 1
Primary Indications for Late TNK Administration
Evidence of ongoing myocardial ischemia - Patients with persistent clinical symptoms (chest pain) and/or electrocardiographic evidence of ongoing ischemia, even when symptoms started >12 hours ago 1
Large area of myocardium at risk - When a substantial portion of the myocardium is jeopardized, as evidenced by extensive ST-segment elevation on ECG or large anterior infarctions 1
Hemodynamic instability - Patients with cardiogenic shock, hypotension, or other signs of hemodynamic compromise 1
PCI unavailability - When primary PCI cannot be performed in a timely manner (within 120 minutes of first medical contact) 1, 2
Important Considerations and Contraindications
Risk-benefit assessment - The risk of bleeding complications increases with delayed administration, particularly intracranial hemorrhage (approximately 0.5%) 2, 3
Absolute contraindications must still be observed regardless of timing 1, 2:
- Any prior intracranial hemorrhage
- Known structural cerebral vascular lesions
- Known malignant intracranial neoplasms
- Ischemic stroke within 3 months
- Suspected aortic dissection
- Active bleeding or bleeding diathesis
- Significant closed-head or facial trauma within 3 months
- Severe uncontrolled hypertension
ST depression only - TNK should not be administered to patients with only ST-segment depression (except when true posterior STEMI is suspected) due to risk of hemorrhage 1
Evidence and Recommendations
The 2025 ACC/AHA guidelines state: "In patients with STEMI and symptom onset of 12 to 24 hours, transfer to a PCI-capable hospital for PPCI is reasonable to reduce infarct size and MACE" (Class 2a, Level B-NR) 1
For late presenters (>12 hours) with hemodynamic instability or large infarct size: "Fibrinolytic administration may outweigh potential risks when timely PPCI is not possible" 1
The ESC guidelines similarly indicate that "reperfusion therapy (preferably primary PCI) is indicated if there is evidence of ongoing ischemia, even if symptoms may have started >12 h beforehand" (Class I, Level C) 1
The 2013 ACCF/AHA guidelines provide a Class IIa recommendation: "In the absence of contraindications and when PCI is not available, fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia within 12 to 24 hours of symptom onset and a large area of myocardium at risk or hemodynamic instability" 1
Administration Protocol When Used Beyond 12 Hours
Weight-based dosing remains the same regardless of timing 4:
- <60 kg: 30 mg
- 60-69 kg: 35 mg
- 70-79 kg: 40 mg
- 80-89 kg: 45 mg
- ≥90 kg: 50 mg
Adjunctive therapy should include 4:
- Aspirin (loading dose 150-300 mg orally or 80-150 mg IV)
- Clopidogrel
- Anticoagulation (enoxaparin or unfractionated heparin)
Post-administration - All patients should be transferred to a PCI-capable center as soon as feasible after fibrinolysis 1, 4, 2
Clinical Pitfalls to Avoid
Failing to recognize ongoing ischemia - Symptoms may be atypical or stuttering, especially in elderly or diabetic patients 1
Underestimating myocardium at risk - Careful ECG interpretation is essential to identify extensive ST elevation or true posterior MI 1
Overlooking contraindications - The risk of bleeding complications increases with delayed administration 1, 2
Not arranging timely transfer - Fibrinolysis should be followed by transfer to a PCI-capable center as soon as possible 1, 4
Inappropriate use in stable patients >24 hours - Routine PCI of a totally occluded artery >24 hours after symptom onset in stable patients without signs of ischemia is not recommended (Class III, Level A) 1