What are the absolute and relative contraindications to thrombolytic therapy for acute myocardial infarction?

Contraindications to Thrombolytic Therapy in Acute Myocardial Infarction

Thrombolytic therapy is contraindicated in STEMI patients with any prior intracranial hemorrhage, ischemic stroke within 3 months, known structural cerebral vascular lesions, active bleeding, or isolated ST-segment depression on ECG. 1, 2, 3

Absolute Contraindications

Neurological

• Any prior intracranial hemorrhage at any time – this is a permanent exclusion from fibrinolysis 1, 2, 3
• Ischemic stroke within the preceding 3 months (some guidelines specify 6 months) 1, 2, 3
• Known structural cerebral vascular lesions such as arteriovenous malformation or aneurysm 1, 2, 3
• Known malignant intracranial neoplasm (primary or metastatic) 1, 2, 3
• Significant closed-head or facial trauma within 3 months 1, 2
• Intracranial or intraspinal surgery within the past 2 months 3

Bleeding-Related

• Active internal bleeding (excluding menses) 1, 2, 3
• Known bleeding diathesis including thrombocytopenia or coagulopathy 1, 2, 3

Cardiovascular

• Suspected aortic dissection 1, 2, 3
• Severe uncontrolled hypertension (systolic BP >180 mmHg or diastolic BP >110 mmHg) unresponsive to emergency therapy 1, 2, 3

ECG-Based Critical Exclusion

• Isolated ST-segment depression without posterior MI or aVR elevation – this represents NSTEMI where fibrinolysis is harmful, not beneficial 4, 3
• Fibrinolysis should only be given for persistent ST-segment elevation or new left bundle branch block 1, 4, 3

Agent-Specific

• Prior streptokinase or anistreplase administration within 6 months to 10 years due to antibody formation causing severe allergic reactions and impaired efficacy 1, 2, 3

Relative Contraindications

These require careful risk-benefit assessment but do not automatically exclude thrombolysis, particularly in large infarctions or hemodynamic instability 1, 2, 3:

• Transient ischemic attack within preceding 6 months 1, 2
• History of prior ischemic stroke >3 months ago, dementia, or known intracranial pathology not meeting absolute criteria 1, 2, 3
• Chronic severe poorly controlled hypertension 1, 2
• Severe hypertension on presentation (SBP >180 mmHg or DBP >110 mmHg but responsive to treatment) 1, 2, 3
• Traumatic or prolonged CPR (>10 minutes) 1, 2, 3
• Major surgery within the preceding 3 weeks (non-cranial) 1, 2, 3
• Recent internal bleeding within 2-4 weeks 1, 2, 3
• Gastrointestinal bleeding within the last month 1, 2
• Non-compressible vascular punctures 1, 2, 3
• Pregnancy or within 1 week postpartum 1, 2, 3
• Active peptic ulcer disease 1, 2, 3
• Current oral anticoagulant therapy (higher INR increases bleeding risk) 1, 2, 3
• Advanced liver disease 1, 2
• Infective endocarditis 1, 2

Clinical Decision Algorithm

Step 1: Confirm STEMI diagnosis – ≥2 contiguous leads with ST-segment elevation or new LBBB, with symptom onset ≤12 hours 1, 3

Step 2: Screen for absolute contraindications – presence of any single absolute contraindication eliminates fibrinolysis as an option 1, 2, 3

Step 3: Assess PCI availability – if primary PCI can be performed within 120 minutes of first medical contact, transfer for PCI is preferred over thrombolysis 1, 3

Step 4: If PCI unavailable and no absolute contraindications exist – administer fibrinolytic therapy immediately, preferably in the pre-hospital setting 1, 3

Step 5: Evaluate relative contraindications – balance bleeding risk against ischemic benefit considering infarct size, hemodynamic status, and symptom duration 1, 2, 3

Step 6: Agent selection – use fibrin-specific agents (tenecteplase, alteplase, or reteplase) with aspirin, clopidogrel, and enoxaparin or UFH 1, 3

Critical Clinical Pitfalls to Avoid

Advanced age is NOT a contraindication – elderly patients (>75 years) derive the greatest absolute mortality benefit from thrombolysis, and only approximately 9% have true absolute contraindications 1, 2, 3

Cardiogenic shock is NOT a contraindication – patients with STEMI and shock who cannot receive immediate PCI should receive fibrinolysis 1, 3

Relative contraindications should not automatically exclude treatment – in patients with large infarcts, hemodynamic instability, or when PCI is unavailable, mortality benefit usually outweighs bleeding risk 1, 2, 3

Do not confuse surgical timing – intracranial/intraspinal surgery within 2 months is absolute, whereas non-cranial surgery within 3 weeks is only relative 3

Recent gastrointestinal bleeding context matters – in stable STEMI this is absolute, but in massive pulmonary embolism with shock it becomes relative because survival benefit outweighs bleeding risk 1, 2

Symptom onset >12 hours is not absolute – if ongoing ischemia, large myocardium at risk, or hemodynamic instability persists and PCI is unavailable, thrombolysis may still be beneficial 1, 3

Evidence Quality and Nuances

The ACC/AHA and ESC guidelines provide the most comprehensive and consistent contraindication lists 1, 3. The true incidence of absolute contraindications is very low—only 1.4% in the TETAMI trial—suggesting that thrombolysis is being underused due to perceived rather than actual contraindications 1, 5. Research demonstrates that clinicians withhold thrombolysis in 35-95% of cases with perceived contraindications despite little evidence of increased hemorrhagic risk 5. The major bleeding rate from randomized trials is approximately 13%, with intracranial hemorrhage occurring in 1.8% of patients 1.