What are the guidelines for thrombolysis using alteplase (tissue plasminogen activator) and thrombectomy in acute ischemic stroke management?

Guidelines for Thrombolysis and Thrombectomy in Acute Ischemic Stroke Management

Intravenous thrombolysis with alteplase should be administered as soon as possible to eligible patients within 4.5 hours of stroke symptom onset, and mechanical thrombectomy should be performed in eligible patients with large vessel occlusion within 24 hours of symptom onset when appropriate imaging criteria are met. 1

Intravenous Thrombolysis with Alteplase

Timing and Dosage

• IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 min with initial 10% of dose given as bolus over 1 min) is recommended for eligible patients who can be treated within 4.5 hours of ischemic stroke symptom onset or last known well 1
• Treatment should be initiated as soon as possible after patient arrival and CT scan, with a target door-to-needle time of less than 60 minutes in 90% of treated patients, and a median door-to-needle time of 30 minutes 1
• Only assessment of blood glucose must precede the initiation of IV alteplase in all patients 1

Extended Time Windows

• For patients with acute ischemic stroke who awake with stroke symptoms or have unclear time of onset >4.5 hours from last known well, IV alteplase administered within 4.5 hours of stroke symptom recognition can be beneficial if MRI shows DWI-FLAIR mismatch 1
• For patients with acute ischemic stroke within 4.5–9 hours of symptom onset who have CT or MRI core/perfusion mismatch, and for whom mechanical thrombectomy is either not indicated or not planned, consider intravenous thrombolysis with alteplase 1, 2

Blood Pressure Management

• Patients with acute ischemic stroke and acute hypertension who are otherwise eligible for IV thrombolysis should have their BP lowered below 185/110 mm Hg before IV thrombolysis is initiated 1

Special Populations and Considerations

• For patients >80 years of age presenting in the 3- to 4.5-hour window, IV alteplase is safe and can be as effective as in younger patients 1
• Within 3 hours from symptom onset, treatment of patients with mild ischemic stroke symptoms that are judged as non-disabling may be considered 1
• IV alteplase is reasonable in patients with a seizure at the time of onset of acute stroke if evidence suggests that residual impairments are secondary to stroke and not a postictal phenomenon 1
• IV alteplase may be reasonable in patients who have a history of warfarin use and an INR ≤1.7 1, 3
• Patients on direct oral anticoagulants (DOACs) should not routinely receive alteplase, though endovascular thrombectomy may be considered in these cases 1

Mechanical Thrombectomy

Patient Selection

• Patients should receive mechanical thrombectomy with a stent retriever or with direct aspiration if they meet all the following criteria:

  1. Age ≥18 years
  2. Pre-stroke mRS score of 0–1
  3. Causative occlusion of the internal carotid artery or MCA (M1)
  4. NIHSS score of ≥6
  5. ASPECTS of ≥6
  6. Treatment can be initiated (groin puncture) within 6 hours of symptom onset or last known well 1

• Mechanical thrombectomy is also recommended between 6 and 24 hours in patients who have sizable mismatch between ischemic core (by CTP or MRI-DWI) and either clinical deficits or area of hypoperfusion (by CTP or MRI-PWI) 1

Imaging Selection

• Patients with clinically suspected large vessel occlusion (LVO) should have non-invasive angiography (e.g., CTA) 1
• Patients with acute ischemic stroke within 6–24 hours of time last known well who have a LVO in the anterior circulation should have advanced imaging (CTP or DW-MRI, with or without MRI perfusion) to determine eligibility for mechanical thrombectomy 1

Procedural Considerations

• Eligible patients should receive IV thrombolysis even if mechanical thrombectomy is being considered 1, 4
• Do NOT evaluate responses to IV thrombolysis before proceeding with catheter angiography for mechanical thrombectomy 1
• The technical goal of mechanical thrombectomy should be reperfusion to a modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b/3 1
• In patients under consideration for mechanical thrombectomy, observation after IV alteplase to assess for clinical response should not be performed, as any delay to mechanical thrombectomy is associated with worse outcomes 1

Common Pitfalls and Caveats

• Delays in evaluation and initiation of therapy should be avoided, as the opportunity for improvement is greater with earlier treatment 1
• For the 3-to-4.5-hour window, additional exclusion criteria apply: patients older than 80 years, those taking oral anticoagulants with an INR ≤1.7, those with a baseline NIHSS score >25, or those with both a history of stroke and diabetes 1 (Note: More recent guidelines have relaxed some of these criteria, particularly for patients >80 years 1)
• Electrocardiography and other blood tests (complete cell count, serum electrolytes and creatinine, INR and partial thromboplastin time, serum troponin) should be obtained but should not delay the initiation of reperfusion therapy 1
• Tenecteplase administered as a 0.4-mg/kg single IV bolus has not been proven to be superior or non-inferior to alteplase but might be considered as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion 1, 5
• The use of sonothrombolysis as adjuvant therapy with IV thrombolysis is not recommended 1

By following these evidence-based guidelines for thrombolysis and thrombectomy in acute ischemic stroke, clinicians can optimize patient outcomes by providing timely and appropriate reperfusion therapies based on individual patient characteristics and imaging findings 1.