Which patients are eligible to receive Tissue Plasminogen Activator (TPA)?

Eligibility Criteria for Tissue Plasminogen Activator (TPA) in Acute Ischemic Stroke

TPA should be administered to eligible patients with acute ischemic stroke who can be treated within 4.5 hours of symptom onset, with stricter criteria applied for the 3-4.5 hour window. 1

Time Windows for TPA Administration

0-3 Hour Window (Level A Recommendation)

• Patients meeting NINDS inclusion/exclusion criteria 1
• Higher efficacy and better outcomes compared to later treatment 1
• FDA-approved indication 1

3-4.5 Hour Window (Level B Recommendation)

• Patients meeting ECASS III inclusion/exclusion criteria 1
• Additional exclusion criteria apply (see below) 1
• Not FDA-approved but recommended by AHA/ASA 1

Inclusion Criteria for TPA Administration

• Diagnosis of ischemic stroke causing measurable neurologic deficit 1
• Age ≥18 years 1
• Onset of symptoms within treatment window (0-4.5 hours) 1

Exclusion Criteria for All TPA Patients (0-4.5 Hours)

Bleeding Risk Factors

• Head trauma or prior stroke in previous 3 months 1
• Symptoms suggesting subarachnoid hemorrhage 1
• History of previous intracranial hemorrhage 1
• Arterial puncture at noncompressible site in previous 7 days 1
• Major surgery within prior 14 days 2
• Gastrointestinal or genitourinary hemorrhage within previous 21 days 2

Coagulation Abnormalities

• Platelet count <100,000/mm³ 1
• Current use of anticoagulant with INR >1.7 or PT >15 seconds 1
• Heparin received within 48 hours resulting in elevated aPTT 1

Blood Pressure and Other Factors

• Elevated blood pressure (systolic >185 mmHg or diastolic >110 mmHg) 1
• Blood glucose <50 mg/dL (2.7 mmol/L) 1
• CT demonstrating multilobar infarction (hypodensity >1/3 cerebral hemisphere) 1

Additional Exclusion Criteria for 3-4.5 Hour Window

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

Special Considerations

Elderly Patients (≥80 years)

• Increased risk of symptomatic intracranial hemorrhage (sICH) and death 3
• Should only be considered for treatment in the 0-3 hour window 1
• Treatment decisions should be made with caution, especially with longer onset-to-treatment times 3

Mild Stroke or Rapidly Improving Symptoms

• Common reason for exclusion in practice 4
• Clinical judgment needed, as some patients with mild symptoms may still benefit from treatment

Administration Protocol

• Dose: 0.9 mg/kg (maximum 90 mg) 1
• Administration: 10% as bolus over 1 minute, remaining 90% as infusion over 60 minutes 1
• Target door-to-needle time: <60 minutes, ideally <30 minutes 1

Post-Administration Monitoring

• Neurological assessments every 15 minutes during and after infusion for 2 hours 2
• Then every 30 minutes for 6 hours, and hourly until 24 hours post-treatment 2
• Follow-up CT or MRI at 24 hours before starting antiplatelet therapy 2
• Blood pressure should be maintained below 180/105 mmHg 2

Common Pitfalls to Avoid

1. Delayed treatment - Efficacy decreases and risk increases with time from symptom onset 2
2. Protocol violations - Associated with increased risk of symptomatic intracranial hemorrhage 1
3. Inadequate blood pressure control - Can increase bleeding risk
4. Failure to recognize contraindications - Particularly important in the 3-4.5 hour window
5. Inappropriate exclusion - Some patients may be incorrectly deemed ineligible due to mild symptoms 4

Despite the risk of symptomatic intracranial hemorrhage (6.4% with TPA vs 0.6% with placebo), treatment with TPA within the appropriate time window significantly improves functional outcomes at three months 5, with patients at least 30% more likely to have minimal or no disability.