What are the absolute contraindications for thrombolysis with tissue plasminogen activator (tPA) in patients with acute ischemic stroke?

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Absolute Contraindications for Stroke Thrombolysis

Intracranial hemorrhage on imaging is the only universally absolute contraindication to thrombolysis in acute ischemic stroke. 1

Imaging-Based Absolute Contraindication

  • Presence of intracranial hemorrhage (excluding microbleeds) on non-contrast CT or MRI is an absolute contraindication to IV tPA administration 1
  • Imaging must be completed and interpreted by a physician with appropriate expertise before initiating thrombolytic therapy 1

Historical and Clinical Absolute Contraindications (0-3 Hour Window)

Based on the 2010 AHA guidelines, the following are considered absolute contraindications within the standard 3-hour treatment window 1:

Prior Neurological Events

  • Head trauma or prior stroke within the previous 3 months 1
  • History of previous intracranial hemorrhage 1
  • Symptoms suggesting subarachnoid hemorrhage 1

Bleeding Risk Factors

  • Active bleeding on examination 1
  • Acute bleeding diathesis, including 1:
    • Platelet count <100,000/mm³
    • Heparin received within 48 hours resulting in aPTT above upper limit of normal
    • Current anticoagulant use with INR >1.7 or PT >15 seconds
  • Arterial puncture at non-compressible site within previous 7 days 1

Blood Pressure and Metabolic

  • Elevated blood pressure: systolic >185 mm Hg or diastolic >110 mm Hg 1
  • Blood glucose concentration <50 mg/dL (2.7 mmol/L) 1

Imaging Findings

  • CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemisphere) 1

Additional Absolute Contraindications (3-4.5 Hour Window)

For patients being considered for treatment between 3-4.5 hours from symptom onset, the following additional exclusions apply 1:

  • Age >80 years 1
  • Severe stroke (NIHSS >25) 1
  • Taking oral anticoagulant regardless of INR 1
  • History of both diabetes AND prior ischemic stroke 1

Drug-Specific Contraindication

  • Known hypersensitivity to alteplase or any component of the formulation 2

Important Caveats

Treatment can be initiated before coagulation studies are available in patients without recent anticoagulant or heparin use, but must be discontinued if INR >1.7 or PT is elevated 1

Treatment can be initiated before platelet count is available in patients without history of thrombocytopenia, but must be discontinued if platelet count <100,000/mm³ 1

Many listed contraindications may be relative rather than absolute in clinical practice—emerging evidence suggests that approximately 50% of patients treated "off-label" with contraindications had similar rates of symptomatic intracerebral hemorrhage compared to those without contraindications 3, and patients with prior cerebral hemorrhage may not have increased bleeding risk with thrombolysis 4. However, these remain formal contraindications in current guidelines 1.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The safety and efficacy of tPA intravenous thrombolysis for treating acute ischemic stroke patients with a history of cerebral hemorrhage.

Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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