What are the inclusion criteria for thrombolytics (tissue plasminogen activators) in suspected acute ischemic stroke?

Inclusion Criteria for Thrombolytics in Suspected Stroke

Intravenous tissue plasminogen activator (tPA) should be administered to eligible patients with acute ischemic stroke within 3 hours of symptom onset, with consideration for extended treatment up to 4.5 hours in carefully selected patients. 1

Primary Inclusion Criteria

Time Window

• Within 3 hours of symptom onset: Strongest evidence for benefit with Number Needed to Treat (NNT) of 8 1
• 3-4.5 hours after symptom onset: Less robust benefit (NNT of 14) but still recommended in selected patients 1, 2

Clinical Criteria

• Measurable deficit on NIH Stroke Scale 2
• Clearly defined time of symptom onset 2
• Baseline CT scan showing no evidence of hemorrhage 2

Imaging Criteria

• No evidence of intracranial hemorrhage on initial brain CT 2
• For patients treated within 3 hours: The presence of early infarct signs on CT (even if involving >1/3 of the middle cerebral artery territory) does not preclude treatment 2
• For patients in the 3-4.5 hour window: ASPECTS score of 6 or higher is preferred (indicating small-to-moderate ischemic core) 2
• If CT or MR perfusion is used, it should demonstrate a perfusion mismatch of at least 20% 2

Blood Pressure Requirements

• Systolic BP <185 mmHg and diastolic BP <110 mmHg before initiation of IV thrombolysis 2
• BP must be maintained <180/105 mmHg for the first 24 hours after IV thrombolysis 2

Additional Considerations for 3-4.5 Hour Window

Patients in the 3-4.5 hour window must also meet these additional criteria 2:

• Age ≤80 years
• No severe stroke (NIHSS >25)
• No combination of previous stroke and diabetes mellitus
• No oral anticoagulant use (regardless of INR)

Exclusion Criteria

Time-Related Exclusions

• Symptom onset >4.5 hours 2
• Unknown time of symptom onset 2

Medical History Exclusions

• Another stroke or serious head injury within the preceding 3 months 2
• Major surgery within prior 14 days 2
• History of intracranial hemorrhage 2
• Gastrointestinal or genitourinary hemorrhage within previous 21 days 2
• Arterial puncture at a noncompressible site within previous 7 days 2

Clinical Exclusions

• Rapidly improving or minor symptoms 2
• Symptoms suggestive of subarachnoid hemorrhage 2
• Seizure at onset of stroke (although this is being reconsidered with newer imaging techniques) 2, 3

Laboratory Exclusions

• Use of anticoagulation with elevated values:
  • Patients receiving heparin within 48 hours with elevated PTT 2
  • PT >15 seconds or INR >1.6 2, 4
  • Platelet count <100,000 2
• Glucose level <50 mg/dL or >400 mg/dL 2

Implementation Considerations

System Requirements

• Rapid access to brain imaging and interpretation 2
• Protocols for drug administration and monitoring 2
• Ability to manage complications 2
• Target door-to-needle time of <60 minutes in 90% of treated patients 2

Post-Treatment Management

• Frequent neurological assessments 1
• Blood pressure monitoring every 15 minutes for 2 hours, then every 30 minutes for 6 hours 1
• No anticoagulants or antiplatelets for 24 hours after tPA administration 1

Common Pitfalls to Avoid

• Delaying treatment while waiting for laboratory results in otherwise eligible patients 1
• Inappropriate blood pressure management 1
• Failure to recognize stroke mimics 1
• Initiating anticoagulation too early (within 24 hours of IV tPA) 1
• Treating beyond recommended time windows, which significantly increases hemorrhage risk 1

The decision to administer thrombolytics should be made rapidly but carefully, weighing the potential benefits against the risks of treatment. The risk of symptomatic intracerebral hemorrhage is approximately 6% with an NNH of 17 1, but this is outweighed by the mortality and morbidity benefits in appropriately selected patients.