What are the absolute contraindications for administering tissue plasminogen activator (tPA) in a patient with acute ischemic stroke?

Absolute Contraindications for tPA in Acute Ischemic Stroke

tPA is absolutely contraindicated in patients with intracranial hemorrhage on imaging, prior intracranial hemorrhage at any time, recent stroke or head trauma within 3 months, uncontrolled hypertension (SBP >185 or DBP >110 mmHg), active bleeding, coagulopathy (INR >1.7, platelets <100,000/mm³), intracranial neoplasm/AVM/aneurysm, recent intracranial/intraspinal surgery, symptoms suggesting subarachnoid hemorrhage, arterial puncture at noncompressible site within 7 days, blood glucose <50 mg/dL, or multilobar infarction (>1/3 cerebral hemisphere) on CT. 1

Hemorrhagic Contraindications

• Any evidence of intracranial hemorrhage on CT or MRI is an absolute contraindication 1
• History of any prior intracranial hemorrhage at any time in the patient's history absolutely contraindicates tPA 1
• Symptoms suggesting subarachnoid hemorrhage (severe headache, neck stiffness, sudden onset) preclude treatment 1
• Active internal bleeding at time of presentation is an absolute contraindication 1

Important nuance: Small numbers of microhemorrhages (<5) detected on gradient-echo MRI sequences do NOT contraindicate tPA administration 1

Recent Neurological Events

• Significant head trauma within the previous 3 months absolutely contraindicates tPA 1
• Prior ischemic stroke within the previous 3 months is an absolute contraindication 1, 2
  • The risk of symptomatic intracranial hemorrhage is particularly elevated within the first 14 days after prior stroke (16.3% vs 4.8% baseline; adjusted OR 3.7) 2
• Recent intracranial or intraspinal surgery is an absolute contraindication 1

Structural Brain Abnormalities

• Intracranial neoplasm, arteriovenous malformation, or aneurysm absolutely contraindicates tPA 1
• CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemisphere) is an absolute contraindication 1

Critical pitfall to avoid: Minor ischemic changes on baseline CT are NOT contraindications to treatment 3, 1

Coagulation and Hematologic Contraindications

• Acute bleeding diathesis, including platelet count <100,000/mm³ is an absolute contraindication 1
• INR >1.7 absolutely contraindicates tPA 1
• Arterial puncture at a noncompressible site within the previous 7 days is an absolute contraindication 1

Practical consideration: Treatment can be initiated before coagulation results are available in patients without recent anticoagulant or heparin use, but must be discontinued if INR >1.7 or platelet count <100,000/mm³ when results return 1

Blood Pressure Contraindications

• Elevated blood pressure: systolic >185 mmHg or diastolic >110 mmHg is an absolute contraindication 1
• Blood pressure must be reduced to <185/110 mmHg before tPA administration and maintained ≤180/105 mmHg for 24 hours post-treatment 1

Metabolic Contraindications

• Blood glucose concentration <50 mg/dL (2.7 mmol/L) is an absolute contraindication 1

Additional Exclusion Criteria for 3-4.5 Hour Window

When treating between 3-4.5 hours from symptom onset, the following additional absolute contraindications apply:

• Age >80 years is an additional exclusion criterion for the 3-4.5 hour window 1
• Severe stroke with NIHSS >25 is an additional exclusion criterion 1
• Taking any oral anticoagulant regardless of INR is an additional exclusion criterion 1
• History of both diabetes mellitus AND prior ischemic stroke (the combination) is an additional exclusion criterion 1

Relative Contraindications (Require Careful Risk-Benefit Assessment)

• Only minor or rapidly improving stroke symptoms (clearing spontaneously) 1
• Pregnancy 1
• Seizure at onset with postictal residual neurological impairments 1
• Major surgery or serious trauma within previous 14 days 1
• Recent gastrointestinal or urinary tract hemorrhage within previous 21 days 1
• Recent acute myocardial infarction within previous 3 months 1

Special Anticoagulation Considerations

tPA should not routinely be administered to patients on direct oral anticoagulants (DOACs) presenting with acute ischemic stroke until there is a commercially available and validated assessment tool for DOAC levels 3