Thrombolysis in Acute Ischemic Stroke
Intravenous recombinant tissue plasminogen activator (r-tPA/alteplase) at 0.9 mg/kg (maximum 90 mg) is the recommended treatment for acute ischemic stroke patients within 4.5 hours of symptom onset, with strongest evidence for treatment within 3 hours. 1, 2
Timing of Thrombolysis
- Within 3 hours: Strongly recommended (Grade 1A) 2
- 3-4.5 hours: Suggested but with lower evidence quality (Grade 2C) 2
- Beyond 4.5 hours: Not recommended (Grade 1B) 2
Administration Protocol
Pre-Treatment Requirements
- Blood pressure must be <185/110 mmHg before initiating thrombolysis 1, 2
- Rapid neuroimaging (non-contrast CT) to rule out intracranial hemorrhage 1
- CT angiography to identify vessel occlusions when possible 1
Dosing and Administration
- Dose: 0.9 mg/kg with maximum dose of 90 mg 1, 2
- Administration: 10% as bolus over 1 minute, remaining 90% as continuous infusion over 60 minutes 2, 1
- Door-to-needle time: Target <60 minutes in 90% of patients (median 30 minutes) 1
Blood Pressure Management
- Pre-treatment: Maintain BP <185/110 mmHg 2, 1
- During/after treatment: Maintain BP <180/105 mmHg for 24 hours 1
- If BP cannot be maintained below target levels, do not administer r-tPA 2
BP Management Options
| BP Level | Treatment |
|---|---|
| Systolic >185 mmHg or diastolic >110 mmHg | Labetalol 10-20 mg IV over 1-2 min (may repeat once) OR Nicardipine drip 5 mg/h, titrate up by 2.5 mg/h [2] |
| Diastolic >140 mmHg | Sodium nitroprusside 0.5 μg/kg/min IV infusion [2] |
Monitoring During and After Treatment
- Every 15 minutes during infusion and for 2 hours after
- Every 30 minutes for next 6 hours
- Every hour for 16 hours 2, 1
Contraindications for Thrombolysis
- Symptom onset >4.5 hours or unknown time of onset
- Another stroke or serious head injury within preceding 3 months
- Major surgery within prior 14 days
- History of intracranial hemorrhage
- Gastrointestinal or genitourinary hemorrhage within previous 21 days 1
Alternative Thrombolytic Approaches
Intraarterial Thrombolysis
- Consider for patients with proximal cerebral artery occlusions not eligible for IV r-tPA
- Must be initiated within 6 hours of symptom onset (Grade 2C) 2
- Extends treatment window to 6 hours after onset 2
Mechanical Thrombectomy
- Indicated for patients with proximal large vessel occlusions
- Can be performed within 6 hours of symptom onset
- Selected patients may be eligible up to 24 hours based on imaging criteria 1
- Evidence suggests against routine use (Grade 2C), but may be considered in carefully selected patients 2
Post-Thrombolysis Management
Antiplatelet Therapy
- Aspirin 160-325 mg should be given within 24-48 hours after stroke onset
- Delay aspirin for 24 hours in patients treated with IV alteplase 1, 2
- Wait until 24-hour post-thrombolysis scan confirms absence of intracranial hemorrhage 1
VTE Prophylaxis
- Prophylactic-dose subcutaneous heparin (preferably LMWH) should start between days 2-4 for patients with restricted mobility 1
- Intermittent pneumatic compression devices can be used as an alternative 1, 2
- Avoid elastic compression stockings (Grade 2B) 2, 1
Complications Management
Symptomatic Intracranial Hemorrhage
- Major risk of thrombolysis (2.4% vs 0.2% with placebo in 3-4.5 hour window) 3
- Higher risk when administered beyond 3 hours 4
- Monitor for neurological deterioration
Angioedema
- Manage with antihistamines, glucocorticoids, and standard airway management as needed 1
Emerging Alternatives
Tenecteplase is gaining attention as a potential alternative to alteplase with practical workflow advantages and possibly superior efficacy in large vessel recanalization 5, though alteplase remains the standard of care based on current guidelines.
Long-term Management
After acute treatment, long-term antiplatelet therapy is indicated with one of:
- Aspirin 75-100 mg daily
- Clopidogrel 75 mg daily
- Aspirin/extended-release dipyridamole 25/200 mg twice daily 1, 2
Clopidogrel or aspirin/extended-release dipyridamole are suggested over aspirin alone (Grade 2B) 2.