What are the indications for IV (intravenous) thrombolysis with alteplase (tissue plasminogen activator) and mechanical thrombectomy in ischemic stroke patients?

Indications for IV Thrombolysis and Mechanical Thrombectomy in Ischemic Stroke Patients

IV thrombolysis with alteplase is recommended for selected patients within 4.5 hours of ischemic stroke symptom onset, while mechanical thrombectomy is indicated for patients with large vessel occlusion within 24 hours of symptom onset when specific eligibility criteria are met. 1

IV Thrombolysis (Alteplase) Indications

Time Windows

• 0-3 hours after symptom onset or last known well (Class I, LOE A) 1

  • Strongest evidence for benefit
  • Fewer exclusion criteria compared to later time windows

• 3-4.5 hours after symptom onset (Class I, LOE B-R) 1

  • Additional exclusion criteria apply:
    • 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

• Special scenarios with extended time windows:

  • Wake-up strokes or unclear onset >4.5h: IV alteplase can be beneficial if MRI shows DWI-FLAIR mismatch 1
  • 4.5-9 hours: Consider IV alteplase if CT or MRI shows core/perfusion mismatch 1

Dosing

• 0.9 mg/kg (maximum dose 90 mg) 2
• 10% given as bolus over 1 minute, remaining 90% as infusion over 60 minutes 2

Pre-Treatment Requirements

• Blood pressure must be <185/110 mmHg 1
• Blood glucose >50 mg/dL 1, 2
• Brain imaging (CT or MRI) to exclude hemorrhage 1
• Only blood glucose assessment must precede alteplase initiation 1

Mechanical Thrombectomy Indications

Standard Time Window (0-6 hours)

Patients should receive mechanical thrombectomy if they meet ALL criteria: 1

• Age ≥18 years
• Pre-stroke mRS score of 0-1
• Causative occlusion of the internal carotid artery or MCA (M1)
• NIHSS score ≥6
• ASPECTS of ≥6
• Treatment can be initiated (groin puncture) within 6 hours of symptom onset

Extended Time Window (6-24 hours)

Mechanical thrombectomy is recommended for patients with: 1

• Large vessel occlusion in the anterior circulation
• Sizable mismatch between ischemic core (by CTP or MRI-DWI) and either:
  • Clinical deficits, or
  • Area of hypoperfusion (by CTP or MRI-PWI)

Technical Considerations

• The goal of mechanical thrombectomy should be reperfusion to modified TICI grade 2b/3 1
• Stent retriever or direct aspiration techniques can be used 1
• Mechanical thrombectomy can be considered in patients with occlusion/stenosis of cervical ICA in addition to intracranial LVO 1

Important Clinical Considerations

Imaging Requirements

• All patients with suspected acute stroke should undergo brain imaging without delay 1
• Patients with clinically suspected LVO should have non-invasive angiography (e.g., CTA) 1
• For extended time windows (6-24h), advanced imaging (CTP or DW-MRI) is required 1

Combined Therapy Approach

• Eligible patients should receive IV thrombolysis even if mechanical thrombectomy is being considered 1
• Do NOT wait to evaluate response to IV thrombolysis before proceeding with catheter angiography for mechanical thrombectomy 1

Post-Thrombolysis Management

• BP should be maintained <180/105 mmHg for at least 24 hours after IV alteplase 1
• Monitor neurological status every 15 minutes during infusion and for 2 hours after, every 30 minutes for the next 6 hours, and hourly until 24 hours 2
• Obtain follow-up CT or MRI at 24 hours before starting anticoagulants or antiplatelet agents 2

Common Pitfalls and Caveats

• Incorrect dosing: The alteplase dosing protocol for stroke differs from that used for myocardial infarction 2
• Treatment delays: Time is brain - initiate treatment as quickly as possible 1
• Inadequate BP control: Failure to lower BP below 185/110 mmHg increases hemorrhage risk 2
• Inappropriate exclusions: Some patients who might benefit are excluded due to overly conservative interpretation of guidelines 2
• Antithrombotic therapy: The risk of antithrombotic therapy within 24 hours after IV alteplase is uncertain and should be individualized based on risk-benefit assessment 1
• Age considerations: Younger patients (18-50 years) have lower morbidity and mortality with IV alteplase compared to older patients 3

By following these evidence-based indications and protocols, clinicians can optimize outcomes for patients with acute ischemic stroke through appropriate application of reperfusion therapies.