What are the guidelines for using Alteplase (tissue plasminogen activator) in patients?

Alteplase Use Guidelines for Acute Ischemic Stroke

Alteplase should be administered within 4.5 hours of symptom onset in eligible patients with acute ischemic stroke, with treatment initiated as quickly as possible as time to treatment is strongly associated with improved outcomes. 1

Dosing and Administration

• Dose: 0.9 mg/kg body weight (maximum 90 mg)
• Administration: 10% as initial bolus over 1 minute, remaining 90% as infusion over 60 minutes 1

Time Windows for Administration

0-3 Hours Window (Highest Priority)

• Recommended for all eligible patients regardless of stroke severity
• Provides greatest benefit with strongest evidence (Class I; LOE A) 1
• Includes patients >80 years of age

3-4.5 Hours Window

• Recommended for selected patients meeting specific criteria:
  • Age ≤80 years
  • No history of both diabetes mellitus AND prior stroke
  • NIHSS score ≤25
  • Not taking oral anticoagulants
  • No imaging evidence of ischemic injury involving more than one-third of MCA territory 1

Eligibility Criteria and Contraindications

Blood Pressure Requirements

• BP must be <185/110 mmHg before treatment
• BP should be lowered safely with antihypertensive agents if needed 1

Laboratory Parameters

• Blood glucose >50 mg/dL
• Platelets ≥100,000/mm³
• INR ≤1.7 if on warfarin
• aPTT ≤40 seconds
• PT ≤15 seconds 1

Absolute Contraindications

1. Intracranial hemorrhage on imaging
2. Subarachnoid hemorrhage (suspected or confirmed)
3. History of intracranial hemorrhage
4. Severe head trauma within past 3 months
5. Intracranial/intraspinal surgery within past 3 months
6. Ischemic stroke within past 3 months
7. Active internal bleeding
8. Intracranial neoplasm, AVM, or aneurysm
9. Infective endocarditis
10. Aortic arch dissection
11. GI malignancy or GI bleeding within past 21 days 1

Anticoagulation-Related Contraindications

• Treatment with LMWH at therapeutic doses within previous 24 hours
• Direct thrombin inhibitors or factor Xa inhibitors within 48 hours (unless laboratory tests are normal)
• Concurrent use of glycoprotein IIb/IIIa inhibitors 1

Special Populations and Considerations

Mild Stroke Symptoms

• Treatment may be considered for mild, non-disabling symptoms within 3 hours (Class IIb; LOE C-LD) 1
• Benefits should be weighed against potential risks

Elderly Patients

• Patients >80 years presenting within 3-4.5 hours can be treated safely with comparable effectiveness to younger patients (Class IIa; LOE B-NR) 1
• Advanced age alone is not a contraindication within the 0-3 hour window

Prior Antiplatelet Therapy

• Alteplase is recommended for patients on antiplatelet monotherapy
• Also recommended for patients on dual antiplatelet therapy (e.g., aspirin plus clopidogrel), though with potentially higher bleeding risk 1

End-Stage Renal Disease

• Recommended for patients on hemodialysis with normal aPTT 1

Post-Alteplase Management

Antiplatelet Therapy

• Delay antiplatelet therapy for 24 hours after alteplase administration to reduce bleeding risk 2
• Early administration of antiplatelet therapy (<24 hours) may be considered in specific clinical scenarios, though this requires careful risk assessment 2

Monitoring

• Close neurological monitoring for 24 hours
• Blood pressure control per protocol
• Immediate CT if neurological deterioration occurs

Common Pitfalls to Avoid

1. Delaying treatment while waiting for laboratory results

   • In patients without known coagulopathy, treatment can be initiated before lab results are available but should be discontinued if results show contraindications 1

2. Excluding patients based on mild or improving symptoms

   • Evidence suggests these patients may still benefit from treatment 1

3. Overestimating the significance of early ischemic changes on CT

   • Mild to moderate early ischemic changes are not contraindications 1

4. Missing the time window

   • Treatment should be initiated as quickly as possible as benefit decreases with time 1

5. Inappropriate blood pressure management

   • Ensure BP <185/110 mmHg before treatment and maintain afterward

Remember that the greatest benefit from alteplase is achieved with early treatment, with diminishing returns as time from symptom onset increases. A well-organized stroke system of care is essential to minimize door-to-needle times and maximize patient outcomes.