What are the inclusion and exclusion criteria for thrombolysis with alteplase (tissue plasminogen activator) in acute ischemic stroke patients according to Malaysia stroke guidelines?

Stroke Thrombolysis Inclusion and Exclusion Criteria Based on Malaysia Stroke Guidelines

While Malaysia-specific stroke guidelines are not provided in the evidence, the standard international criteria for IV alteplase in acute ischemic stroke should be applied, following the American Heart Association/American Stroke Association 2018 guidelines which are universally adopted. 1

Inclusion Criteria for IV Alteplase

Standard Time Window (0-4.5 Hours)

Patients with acute ischemic stroke presenting within 4.5 hours of symptom onset or last known well should receive IV alteplase (0.9 mg/kg, maximum 90 mg over 60 minutes with 10% as bolus over 1 minute) if they meet eligibility criteria. 1, 2

Core Inclusion Requirements:

• Clinical diagnosis of acute ischemic stroke causing measurable neurological deficit 1
• Symptom onset clearly defined and within 4.5 hours (or last known well time if onset unclear) 1, 2
• CT or MRI scan excluding intracranial hemorrhage 1, 2
• Age ≥18 years 1
• Blood pressure controlled to <185/110 mmHg before treatment initiation 2, 3

Extended Time Window (4.5-24 Hours)

For patients presenting 4.5-24 hours after symptom onset, IV alteplase can be beneficial if MRI demonstrates DWI-FLAIR mismatch (for wake-up strokes) or CT/MRI perfusion shows salvageable tissue with specific mismatch criteria. 2, 4, 5

Extended Window Requirements:

• Ischemic core volume ≤70 mL 2, 4
• Penumbra ≥10 mL 2, 4
• Mismatch ratio ≥20% 2, 4
• No large vessel occlusion requiring mechanical thrombectomy 4

Exclusion Criteria for IV Alteplase

Absolute Contraindications (0-3 Hours Window):

Hemorrhagic Risk Factors:

• Active internal bleeding 1
• History of intracranial hemorrhage 1
• Intracranial or intraspinal surgery within 3 months 1
• Serious head trauma within 3 months 1
• Intracranial neoplasm, arteriovenous malformation, or aneurysm 1

Coagulation Abnormalities:

• Current use of oral anticoagulants with INR >1.7 1
• Use of direct oral anticoagulants (DOACs) within 48 hours with elevated sensitive laboratory tests 1, 2
• Heparin use within 48 hours with elevated aPTT 1
• Platelet count <100,000/mm³ 1

Clinical Parameters:

• Blood pressure persistently >185/110 mmHg despite treatment 1, 2
• Blood glucose <50 mg/dL 1, 2
• CT or MRI showing multilobar infarction (hypodensity >1/3 cerebral hemisphere) 1

Additional Exclusions for 3-4.5 Hour Window:

The 3-4.5 hour window has more restrictive criteria based on the ECASS-III trial exclusions: 1, 6

• Age >80 years 1, 3
• Any oral anticoagulant use regardless of INR 1, 3
• NIHSS score >25 1, 3
• Combined history of both diabetes mellitus AND prior ischemic stroke 1, 3

Special Clinical Situations

Reasonable to Treat (Class IIa):

• Mild stroke symptoms (NIHSS <5) within 3-4.5 hours if symptoms are potentially disabling 1
• Seizure at stroke onset if evidence suggests residual deficits are from stroke, not postictal phenomenon 1, 2
• History of 1-10 cerebral microbleeds on prior MRI 1
• Diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions (weigh visual loss risk against stroke benefit) 1
• Known sickle cell disease 1
• Procedural stroke from cardiac or cerebral angiography 1

May Be Reasonable (Class IIb):

• >10 cerebral microbleeds on prior MRI (increased sICH risk but may treat if substantial benefit potential) 1
• Pregnancy when benefits outweigh risks of uterine bleeding 1
• Early postpartum period (<14 days after delivery) 1
• Current systemic malignancy with reasonable life expectancy (>6 months) if no coagulation abnormalities 1

Stroke Mimics:

Starting IV alteplase is recommended over delaying treatment for additional diagnostic studies, as symptomatic intracranial hemorrhage risk in stroke mimics is very low. 1

Critical Pre-Treatment Requirements

Mandatory Before Alteplase:

• Blood glucose measurement only (must be obtained but should not delay treatment beyond this) 2, 3
• Non-contrast CT or MRI to exclude hemorrhage 1, 2

Obtain But Do Not Delay Treatment:

• Complete blood count 3
• Serum electrolytes and creatinine 3
• INR and aPTT 3
• Serum troponin 3
• Electrocardiography 3

Time Targets and Administration

Door-to-needle time should be <60 minutes in 90% of patients, with median target of 30 minutes. 2

Dosing Protocol:

• 0.9 mg/kg body weight (maximum 90 mg total) 1, 2
• 10% given as IV bolus over 1 minute 1, 2
• Remaining 90% infused over 60 minutes 1, 2

Common Pitfalls to Avoid

Do not delay IV alteplase to assess clinical response before proceeding with mechanical thrombectomy evaluation, as any delay worsens outcomes. 2, 3

Do not withhold treatment in patients with rapidly improving symptoms, as approximately one-third develop severe subsequent deterioration. 1

For patients >80 years presenting within 3 hours, age alone should not be an exclusion criterion despite the 3-4.5 hour window restriction. 1, 2

Recent myocardial infarction within 3 months is listed as a relative contraindication in US guidelines but is NOT included as contraindication in European guidelines. 1

Prior stroke within 3 months is often considered a contraindication, but case reports demonstrate successful re-treatment as early as 4 days after initial stroke. 1

Cervical artery dissection should not be considered a contraindication, as >50 reported cases show treatment appears safe and effective. 1

Posterior circulation strokes were excluded from major trials but should receive IV alteplase, as outcomes are comparable to anterior circulation strokes. 1