Which patients with acute ischemic stroke are eligible for thrombolytic therapy with alteplase (tissue plasminogen activator)?

Eligibility Criteria for Thrombolytic Therapy with Alteplase in Acute Ischemic Stroke

Patients with acute ischemic stroke are eligible for thrombolytic therapy with alteplase if they can be treated within 4.5 hours of symptom onset or last known well, have no contraindications, and meet specific clinical and imaging criteria. 1, 2

Time Window Eligibility

• Standard treatment window is within 4.5 hours of symptom onset or last known well 1, 2
• Treatment should be initiated as quickly as possible with a target door-to-needle time of less than 60 minutes 2
• For patients with wake-up stroke or unclear time of onset >4.5 hours from last known well, alteplase may be beneficial if MRI shows DWI-FLAIR mismatch 2
• The 3-4.5 hour window has additional exclusion criteria compared to the 0-3 hour window 1, 3

Absolute Contraindications

• Acute intracranial hemorrhage on CT imaging 1
• Extensive regions of clear hypoattenuation (obvious hypodensity) on CT, representing irreversible injury 1
• Ischemic stroke within the past 3 months 1
• Severe head trauma within 3 months 1
• Intracranial/spinal surgery within 3 months 1
• History of intracranial hemorrhage 1
• Suspected subarachnoid hemorrhage 1
• GI malignancy or GI bleeding within 21 days 1
• Coagulopathy (platelets <100,000/mm³, INR >1.7, aPTT >40 s, or PT >15 s) 1
• Treatment dose of low molecular weight heparin within previous 24 hours 1
• Current use of direct thrombin inhibitors or factor Xa inhibitors with abnormal lab values or taken within 48 hours with normal renal function 1
• Concurrent use of glycoprotein IIb/IIIa inhibitors 1
• Infective endocarditis 1

Relative Eligibility Considerations

Stroke Severity

• Patients with mild to moderate stroke symptoms can benefit from alteplase 1
• For mild, non-disabling stroke symptoms within 3 hours, treatment may be considered after weighing risks and benefits 1
• For very severe stroke (NIHSS >25) in the 3-4.5 hour window, benefit is uncertain 1

Age

• Patients >80 years old are eligible for treatment within the 3-4.5 hour window 1, 2

Blood Pressure

• Blood pressure must be controlled to <185/110 mmHg before initiating alteplase 1, 2
• Blood pressure should be maintained <180/105 mmHg for 24 hours after administration 1

Comorbidities and Special Populations

• Preexisting disability: Alteplase may be reasonable in patients with preexisting disability (mRS ≥2) after considering quality of life, social support, and patient preferences 1
• Dementia: Patients with preexisting dementia may benefit from alteplase, considering life expectancy and premorbid function 1
• Seizure at onset: Alteplase is reasonable if residual deficits are due to stroke rather than postictal phenomena 1, 2
• Blood glucose abnormalities: Treatment may be reasonable in patients with initial glucose <50 or >400 mg/dL that are subsequently normalized 1
• Anticoagulation: Alteplase may be reasonable in patients on warfarin with INR ≤1.7 1, 2
• Recent procedures:
  • Lumbar puncture within 7 days: Alteplase may be considered 1
  • Arterial puncture of noncompressible vessel within 7 days: Safety uncertain 1
  • Major trauma (non-head) within 14 days: Carefully consider risks versus benefits 1
  • Major surgery within 14 days: Consider risks of surgical site hemorrhage 1
• Cardiac conditions:
  • Concurrent acute MI: Treatment with alteplase at stroke dose is reasonable 1
  • Recent MI (past 3 months): Reasonable if non-STEMI or STEMI involving right/inferior myocardium; may be reasonable with left anterior STEMI 1
  • Acute pericarditis with major stroke: Treatment may be reasonable 1
  • Left atrial/ventricular thrombus with major stroke: Treatment may be reasonable 1
• Pregnancy: Alteplase may be considered when benefits of treating moderate/severe stroke outweigh risks of uterine bleeding 1
• Malignancy: Patients with systemic malignancy and reasonable life expectancy (>6 months) may benefit if no coagulation abnormalities or recent surgery/bleeding 1

Imaging Considerations

• Cerebral microbleeds (CMBs):
  • 1-10 CMBs on MRI: Alteplase administration is reasonable 1

  • 10 CMBs on MRI: Increased risk of symptomatic ICH; treatment may be reasonable if potential for substantial benefit 1

• Extra-axial intracranial neoplasms: Alteplase is probably recommended 1
• Intracranial vascular malformations: Alteplase may be considered in severe neurological deficits where benefits may outweigh hemorrhage risk 1

Common Pitfalls and Practical Considerations

• Avoid delays in evaluation and treatment initiation, as earlier treatment yields better outcomes 2
• Only blood glucose assessment must precede alteplase administration; other tests should not delay treatment 2
• ECG and other blood tests should be obtained but should not delay thrombolysis 2
• For patients with large vessel occlusion, consider concurrent evaluation for mechanical thrombectomy 1, 2
• Patients with stroke mimics have very low risk of symptomatic hemorrhage; starting alteplase is recommended over delaying for additional diagnostic studies 1
• Observation after alteplase to assess for clinical response should not delay mechanical thrombectomy evaluation in eligible patients 2

Risk of Symptomatic Intracranial Hemorrhage

• The risk of symptomatic intracranial hemorrhage with alteplase is approximately 2-7% 3, 4
• Risk increases with:
  • Longer time from symptom onset 5, 6
  • Higher stroke severity 1
  • Extensive early ischemic changes on CT 1
  • History of multiple cerebral microbleeds 1
  • Advanced age (though treatment still beneficial) 1