What are the contraindications for Tenecteplase (TNK)?

Contraindications for TNK (Tenecteplase)

TNK is absolutely contraindicated in patients with any prior intracranial hemorrhage, active internal bleeding, history of cerebrovascular accident, intracranial/intraspinal surgery or trauma within 2 months, intracranial neoplasm/AVM/aneurysm, known bleeding diathesis, or severe uncontrolled hypertension. 1

Absolute Contraindications

The FDA label and major cardiology guidelines identify the following as absolute contraindications where TNK must never be administered:

• Any prior intracranial hemorrhage - This remains an absolute contraindication regardless of timing or circumstances 2, 3, 1
• Active internal bleeding - Excluding menses 2, 1
• History of cerebrovascular accident 1
• Known structural cerebral vascular lesions - Including arteriovenous malformations 2, 3
• Known malignant intracranial neoplasm - Both primary and metastatic 2, 3
• Ischemic stroke within 3 months - Exception: acute ischemic stroke within 3 hours may be considered 2
• Intracranial or intraspinal surgery or trauma within 2 months 1
• Significant closed head or facial trauma within 3 months 2
• Suspected aortic dissection 2, 3
• Known bleeding diathesis 2, 1
• Severe uncontrolled hypertension - Defined by FDA as meeting their threshold criteria 1

Relative Contraindications

These conditions require careful risk-benefit assessment but are not absolute prohibitions:

• Severe hypertension on presentation - SBP >180 mmHg or DBP >110 mmHg (note: this could be absolute in low-risk STEMI patients) 2, 3, 4
• History of chronic, severe, poorly controlled hypertension 2, 3, 4
• History of prior ischemic stroke >3 months 2, 3
• Dementia or known intracranial pathology - Not covered in absolute contraindications 2, 3
• Traumatic or prolonged CPR - Defined as >10 minutes 2, 3, 4
• Major surgery within 3 weeks 2, 3
• Recent internal bleeding - Within 2-4 weeks 2, 3
• Noncompressible vascular punctures 2, 3
• Pregnancy or within 1 week postpartum 2, 3
• Active peptic ulcer disease 2, 3, 4
• Current oral anticoagulant therapy - Risk increases with higher INR 2, 3

Critical Clinical Decision Points

Timing Considerations

• TNK is indicated within 12 hours of symptom onset for STEMI 3, 5, 1
• Beyond 12 hours, TNK should only be considered when there is ongoing ischemia, large myocardium at risk, or hemodynamic instability AND primary PCI is unavailable 3, 5
• Primary PCI is strongly preferred over TNK when available, especially beyond the 12-hour window 5

Age-Specific Warnings

• Patients >75 years should NOT receive combination therapy with TNK and GP IIb/IIIa inhibitors (abciximab) due to significantly increased intracranial hemorrhage risk 2
• Weight-optimized dosing of TNK (30-50mg based on body weight) has demonstrated lower ICH rates in elderly, low-weight females compared to standard alteplase dosing 6

Bleeding Risk Stratification

Independent predictors of intracranial hemorrhage include:

• Advanced age 4
• Female gender 4
• Prior cerebrovascular disease 4
• Elevated blood pressure at presentation 4

Common Pitfalls to Avoid

Do not consider these as contraindications:

• Diabetes mellitus or diabetic retinopathy - These are NOT contraindications to TNK 4
• Successful resuscitation - Brief, non-traumatic CPR is not a contraindication; only prolonged/traumatic CPR >10 minutes is a relative contraindication 4
• Body weight estimation errors - TNK dosing can tolerate weight estimation errors up to 20 kg without increased ICH or mortality risk 6

Critical administration errors to avoid:

• Never administer TNK in dextrose-containing IV lines - This causes precipitation; flush lines with 0.9% saline before and after administration 1
• Do not overlook absolute contraindications when considering extended time window treatment 5
• Do not fail to transfer patients to PCI-capable centers after fibrinolytic therapy, even when administered in extended windows 5

Management of Suspected Intracranial Hemorrhage

If neurological deterioration occurs during or after TNK:

• Assume ICH until proven otherwise and immediately discontinue all fibrinolytic, antiplatelet, and anticoagulant therapies 2
• Obtain emergent brain imaging 2
• Administer reversal agents - Cryoprecipitate, fresh frozen plasma, protamine, and platelets as clinically indicated 2
• Obtain immediate consultations - Neurology, neurosurgery, and/or hematology 2