What are the contraindications to tissue plasminogen activator (TPA) or tenecteplase (TNK)?

Contraindications to TPA and TNK

TPA (alteplase) and TNK (tenecteplase) share the same absolute and relative contraindications, with TNK offering a superior safety profile particularly regarding non-cerebral bleeding complications.

Absolute Contraindications

The FDA label for TNKase and major cardiology guidelines identify the following as absolute contraindications 1:

• Active internal bleeding 1
• Any history of cerebrovascular accident (intracranial hemorrhage) - this includes any prior ICH regardless of timing 2, 1
• Intracranial or intraspinal surgery or trauma within 2 months 1
• Intracranial neoplasm (primary or metastatic), arteriovenous malformation, or aneurysm 2, 1
• Known bleeding diathesis 1
• Severe uncontrolled hypertension 1
• Ischemic stroke within 3 months (for cardiac indications) 2
• Suspected aortic dissection 2
• Significant closed-head or facial trauma within 3 months 2

Relative Contraindications

These require careful risk-benefit assessment but are not absolute prohibitions 3, 2:

Cardiovascular & Neurological

• Significant hypertension on presentation (SBP >180 mmHg or DBP >110 mmHg) 2
• History of chronic, severe, poorly controlled hypertension 2
• History of prior ischemic stroke >3 months ago 2
• Dementia or other known intracranial pathology not covered in absolute contraindications 2

Recent Procedures & Trauma

• Traumatic or prolonged CPR (>10 minutes) 3, 2
• Major surgery within 3 weeks 2
• Noncompressible vascular punctures 2

Bleeding Risk Factors

• Recent internal bleeding (within 2-4 weeks) 2
• Active peptic ulcer disease 3, 2
• Current use of oral anticoagulants 2

Other Conditions

• Pregnancy (relative contraindication) 2
• Active bacterial endocarditis or pericarditis 3

Key Clinical Considerations

Bleeding Risk Stratification

Independent predictors of intracranial hemorrhage include 3:

• Advanced age
• Lower body weight
• Female gender
• Prior cerebrovascular disease
• Elevated blood pressure at presentation

The overall risk of intracranial hemorrhage is approximately 0.9-1.0% with modern fibrinolytic protocols 3. Major non-cerebral bleeding occurs in 4-13% of patients, with TNK demonstrating significantly lower rates than alteplase 3.

TNK-Specific Advantages

TNK (tenecteplase) offers important safety benefits over alteplase 3, 4:

• Significantly lower rates of non-cerebral bleeding 3
• Less need for blood transfusion 3
• Weight-optimized dosing can err by up to 20 kg without increased ICH risk 4
• Particularly safer in elderly, low-weight female patients 4

Timing Considerations

• Optimal window: within 12 hours of symptom onset for STEMI 2
• Use beyond 12 hours only in specific circumstances (large area at risk, hemodynamic instability) when PCI unavailable 2
• For ischemic stroke: within 4.5 hours, with TNK showing superior outcomes for excellent functional recovery 5

Common Pitfalls to Avoid

Do not exclude patients based on these factors 3:

• Diabetes or diabetic retinopathy - NOT a contraindication
• Successful resuscitation - NOT a contraindication (but prolonged/traumatic CPR >10 min is relative contraindication)

Critical error prevention 1:

• TNK is incompatible with dextrose-containing solutions - flush lines with 0.9% saline before and after administration 1
• Avoid IM injections and nonessressible puncture sites during and after administration 1
• If arterial puncture necessary, use upper extremity with manual compression for ≥30 minutes 1

When Fibrinolysis Should Be Avoided

Strongly consider primary PCI instead of fibrinolysis when 1:

• Patient presents to PCI-capable center
• Planned PCI within appropriate timeframe (trends toward worse outcomes with TNK + planned PCI vs PCI alone for mortality, cardiogenic shock, CHF, and recurrent MI) 1