What are the contraindications for thrombolysis (thrombolytic therapy) in myocardial infarction (MI)?

Contraindications for Thrombolytic Therapy in Myocardial Infarction

Thrombolytic therapy is contraindicated in patients with active internal bleeding, history of cerebrovascular accident, intracranial/intraspinal surgery or trauma within 2 months, intracranial neoplasm/arteriovenous malformation/aneurysm, known bleeding diathesis, and severe uncontrolled hypertension. 1

Absolute Contraindications

The 2017 European Society of Cardiology (ESC) guidelines clearly outline the following absolute contraindications to thrombolytic therapy in myocardial infarction 2:

• Hemorrhagic stroke or stroke of unknown origin at any time
• Ischemic stroke in preceding 6 months
• Central nervous system damage or neoplasms
• Recent major trauma/surgery/head injury (within preceding 3 weeks)
• Gastrointestinal bleeding within the last month
• Known bleeding disorder

Additionally, the FDA label for tenecteplase (a common thrombolytic agent) lists these absolute contraindications 1:

• Active internal bleeding
• History of cerebrovascular accident
• Intracranial or intraspinal surgery or trauma within 2 months
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Known bleeding diathesis
• Severe uncontrolled hypertension

Relative Contraindications

Relative contraindications represent situations where thrombolytic therapy may still be considered if the potential benefits outweigh the risks 2:

• Transient ischemic attack in preceding 6 months
• Oral anticoagulant therapy
• Pregnancy or within 1 week postpartum
• Non-compressible punctures
• Traumatic resuscitation
• Refractory hypertension (systolic blood pressure >180 mmHg)
• Advanced liver disease
• Infective endocarditis
• Active peptic ulcer

Risk Assessment and Decision Making

When considering thrombolytic therapy, it's crucial to weigh the risk-benefit ratio for individual patients. The risk of intracranial hemorrhage (ICH) increases with:

• Advanced age (>65 years)
• Low body weight (<70 kg)
• Hypertension on presentation
• Use of alteplase 2

The presence of multiple risk factors substantially increases the probability of ICH. Generally, ICH rates below 1% are considered acceptable given the overall favorable benefit-risk profile of thrombolysis, while rates exceeding 1.5% are viewed as unacceptably high 2.

Clinical Considerations

1. Timing is critical: The greatest benefit from thrombolysis occurs when administered within 12 hours of symptom onset, with maximum benefit in the first 3 hours 2.

2. Alternative reperfusion strategies: Primary PCI is preferred over thrombolysis when:

   • Diagnosis of STEMI is in doubt
   • Skilled PCI facility with surgical backup is accessible within 90 minutes
   • Patient is in cardiogenic shock
   • Contraindications to thrombolysis exist
   • Late presentation (>3 hours from symptom onset) 2

3. Special populations: Advanced age alone is not a contraindication to thrombolysis. Elderly patients may actually have a greater absolute benefit from thrombolysis due to their higher baseline risk 3.

Common Pitfalls

1. Overestimating contraindications: Studies suggest thrombolytic therapy is underutilized due to perceived contraindications that may not be evidence-based 4, 3. Clinicians should carefully evaluate whether a contraindication is absolute or relative.

2. Delayed administration: The benefit of thrombolysis decreases with time. Hesitation due to uncertainty about contraindications can lead to harmful delays 5.

3. Failure to consider the risk-benefit ratio: In immediately life-threatening situations (e.g., high-risk PE), some contraindications that would be considered absolute in other contexts might become relative 2.

By understanding these contraindications and applying them appropriately in clinical practice, healthcare providers can optimize the use of thrombolytic therapy for patients with myocardial infarction, potentially saving lives while minimizing the risk of serious adverse events.