What are the contraindications for tissue plasminogen activator (tPA)?

Contraindications for Tissue Plasminogen Activator (tPA)

Tissue plasminogen activator (tPA) is contraindicated in patients with previous hemorrhagic stroke at any time, other strokes or cerebrovascular events within the past year, known intracranial neoplasm, active internal bleeding, and suspected aortic dissection due to the high risk of life-threatening hemorrhage.

Absolute Contraindications

The following conditions represent absolute contraindications to tPA administration:

• Previous intracranial hemorrhage at any time 1
• Other strokes or cerebrovascular events within 1 year 1
• Known intracranial neoplasm, arteriovenous malformation, or aneurysm 1
• Active internal bleeding (excluding menstruation) 1
• Suspected aortic dissection 1
• Recent major trauma, surgery, or head injury (within preceding 3 weeks) 1
• Gastrointestinal bleeding within the past month 1
• Known bleeding disorder 1
• Non-compressible punctures in the past 24 hours (e.g., liver biopsy, lumbar puncture) 1

Relative Contraindications/Cautions

These conditions represent situations where tPA may be used with caution after careful risk-benefit assessment:

• Severe uncontrolled hypertension on presentation (blood pressure >180/110 mm Hg) 1

  • For ischemic stroke: SBP >185 mm Hg or DBP >110 mm Hg are contraindications to tPA within the first 3 hours 1
  • After tPA initiation, BP should be monitored closely with SBP >180 mm Hg or DBP >105 mm Hg requiring intervention to prevent intracerebral bleeding 1

• History of prior cerebrovascular accident or known intracerebral pathology 1

• Current use of anticoagulants in therapeutic doses (INR >2-3) 1

• Recent trauma (within 2-4 weeks), including head trauma or traumatic CPR 1

• Noncompressible vascular punctures 1

• Recent internal bleeding (within 2-4 weeks) 1

• Pregnancy 1

• Active peptic ulcer 1

• History of chronic severe hypertension 1

Special Populations

Children

• tPA is generally not recommended for children with acute ischemic stroke outside of clinical trials 1
• There is no consensus regarding tPA use in older adolescents who otherwise meet standard adult eligibility criteria 1
• If considered in pediatric patients, it is imperative to adhere to the accepted time limits used in adults: intravenous tPA within 3 hours of stroke onset 1

Elderly

• Advanced age alone should not be considered a contraindication for tPA therapy
• The European license previously restricted tPA use in adults >80 years of age 1, but evidence suggests the risk of symptomatic intracerebral hemorrhage is not increased in this population 1

Timing Considerations

• For ischemic stroke, tPA should be administered within 3-4.5 hours of symptom onset 1
• In atrial fibrillation patients with acute stroke, the timing of anticoagulation initiation after tPA depends on stroke severity:
  • TIA: 1 day after acute event
  • Mild stroke (NIHSS <8): 3 days after acute event
  • Moderate stroke (NIHSS 8-15): 6 days after acute event
  • Severe stroke (NIHSS ≥16): 12 days after acute event 1

Pitfalls and Caveats

1. Prestroke antiplatelet therapy increases the risk of symptomatic intracranial hemorrhage with tPA (AOR 1.18), particularly with dual antiplatelet therapy (AOR 1.47) 2

2. Excessive anticoagulation after tPA administration can lead to intracranial hemorrhage. Partial thromboplastin time (PTT) should be closely monitored if heparin is used following tPA 3

3. For patients with ischemic stroke and atrial fibrillation, careful evaluation of hemorrhagic transformation by CT or MRI should be performed before initiating oral anticoagulation 1

4. The combined risk of multiple factors (age >65 years, weight <70 kg, hypertension on admission, and use of tPA) increases the likelihood of intracranial hemorrhage 1

By carefully screening patients for these contraindications and managing modifiable risk factors, the safety profile of tPA can be optimized while preserving its life-saving benefits in appropriate candidates.