Stroke Thrombolysis: Treatment Protocol
Primary Recommendation
For eligible patients with acute ischemic stroke presenting within 3 hours of symptom onset, administer intravenous alteplase (0.9 mg/kg, maximum 90 mg) immediately after CT scan excludes hemorrhage. 1, 2
Time-Based Treatment Algorithm
0-3 Hour Window (Strongest Evidence)
- Administer IV alteplase 0.9 mg/kg (maximum 90 mg total dose) 1, 2
- This is a Class I, Level A recommendation with the strongest evidence for improved functional outcomes 1
- Give 10% of total dose as IV bolus over 1 minute, then remaining 90% as infusion over 60 minutes 2
3-4.5 Hour Window (Moderate Evidence)
- Administer IV alteplase using same dosing protocol 1, 3
- This is a Class I (AHA 2009) or Grade 2C (CHEST 2012) recommendation 1
- Additional exclusion criteria apply: age >80 years, oral anticoagulant use (regardless of INR), NIHSS >25, or both diabetes and prior stroke history 1
- The ECASS III trial demonstrated 52.4% favorable outcomes with alteplase vs 45.2% with placebo (OR 1.34, p=0.04) 3
Beyond 4.5 Hours
- Do not administer IV alteplase (Grade 1B recommendation) 1
- Consider intraarterial thrombolysis within 6 hours for proximal cerebral artery occlusions in patients ineligible for IV therapy (Grade 2C) 1
Dosing Protocol Details
Calculation and Administration
- Total dose: 0.9 mg/kg body weight (maximum 90 mg) 2
- Bolus: 10% of total dose (0.09 mg/kg) IV push over exactly 1 minute 2
- Infusion: 90% of total dose (0.81 mg/kg) IV over 60 minutes 2
- Target door-to-needle time: <60 minutes in 90% of patients, optimal median 30 minutes 2
Critical Pitfall to Avoid
Do not use the myocardial infarction dosing protocol for stroke—this is incorrect and potentially harmful 2
Absolute Contraindications
Imaging-Based
- Evidence of intracranial hemorrhage on CT 2
- Extensive early infarct changes (>33% of MCA territory) 2
Historical
- Intracranial hemorrhage history 2
- Ischemic stroke within 3 months 2
- Severe head trauma within 3 months 2
Laboratory/Coagulation
- Platelets <100,000/mm³ 2
- INR >1.7 2
- aPTT >40 seconds or PT >15 seconds 2
- LMWH within 24 hours 2
- Patients on DOACs (except in comprehensive stroke centers with DOAC level testing and reversal agents) 2
Active Bleeding
Blood Pressure
- Systolic BP >185 mmHg or diastolic BP >110 mmHg that cannot be safely lowered before treatment 2
Special Populations and Relative Considerations
Mild Stroke Symptoms
- For 0-3 hour window: Treatment may be considered but requires weighing risks vs benefits (Class IIb) 1
- For 3-4.5 hour window: May be reasonable (Class IIb, Level B-NR) 1
Preexisting Disability
- Treatment is reasonable despite preexisting disability (mRS ≥2) 1
- Does not independently increase symptomatic ICH risk but may reduce neurological improvement 1
- Consider quality of life, social support, and patient/family preferences 1
Age >80 Years
Recent Procedures
- Lumbar puncture within 7 days: May still administer alteplase (Class IIb) 1, 4
- Epidural catheter in situ: Wait 10 days after catheter removal before alteplase, or 10 days after alteplase before catheter removal 4
- Major surgery within 14 days: Weigh surgical bleeding risk against stroke disability on case-by-case basis 1
Post-Administration Management
Immediate Care
- Hold all antiplatelet agents for 24 hours post-alteplase 2
- Perform 24-hour post-thrombolysis CT scan to exclude hemorrhage before starting antiplatelet therapy 2
- Monitor for angioedema (treat with antihistamines, glucocorticoids, standard airway management) 2
Blood Pressure Management
- Maintain BP <180/105 mmHg for 24 hours after treatment 2
Alternative Agent: Tenecteplase
When to Consider
- May be considered as alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion (Class IIb, Level B-R) 5
- Offers workflow advantages with single-bolus administration vs 1-hour infusion 5
Dosing
- Weight-based single IV bolus: 30 mg for <60 kg, 35 mg for 60-69 kg 5
- Standard stroke dose: 0.25 mg/kg (maximum 25 mg) 5
- Critical: Do not confuse with MI dosing (0.5 mg/kg) 5
Evidence
- Achieves superior reperfusion rates before mechanical thrombectomy (22% vs 10%) 5
- ORIGINAL trial showed noninferior excellent functional outcomes compared to alteplase 5
Adjunctive Therapy
Aspirin
- Administer aspirin 160-325 mg within 48 hours of stroke onset (Grade 1A) 1
- Delay until 24 hours post-alteplase and after CT excludes hemorrhage 2
Anticoagulation
- Do not use therapeutic parenteral anticoagulation in acute phase (Grade 1A) 1
DVT Prophylaxis
- Use prophylactic-dose subcutaneous heparin or intermittent pneumatic compression for immobile patients (Grade 2B) 1
Key Safety Data
Hemorrhage Risk
- Symptomatic ICH rate: 2.4-7.0% with alteplase vs 0.2-1.1% with placebo 3, 6
- Number needed to harm: 17 patients 5
- Any ICH: 27.0% vs 17.6% (p=0.001) 3
Mortality
- No significant mortality difference in 3-4.5 hour window (7.7% vs 8.4%, p=0.68) 3
- 30-day mortality in clinical practice: 13% 6
Efficacy
- Number needed to treat for favorable outcome: 8-14 patients 5
- 35% achieve very favorable outcomes (mRS 0-1) at 30 days 6
- 43% functionally independent (mRS 0-2) at 30 days 6
Common Pitfalls
- Delaying treatment for "perfect" workup—treat based on non-contrast CT alone when within window 2
- Protocol violations occur in 32.6% of cases: treating beyond 3 hours without meeting extended criteria (13.4%), giving anticoagulants within 24 hours (9.3%), treating despite BP >185 mmHg (6.7%) 6
- Removing epidural catheter immediately before/after alteplase creates maximum bleeding risk 4
- Administering alteplase to DOAC patients without specialized testing 2