What is the latest guideline for differentiating ischemic versus hemorrhagic stroke, including thrombotic versus embolic mechanisms, and what is the current recommended tenecteplase (Metalyse) dose?

Latest Stroke Protocol: Differentiation and Thrombolytic Management

Immediate Differentiation: Hemorrhagic vs Ischemic Stroke

Non-contrast CT (NCCT) is the essential first imaging modality to exclude intracranial hemorrhage before any thrombolytic therapy 1. Hemorrhagic stroke shows hyperdense foci on NCCT, and absence of these virtually excludes intracranial hemorrhage. This takes priority over all other imaging and must be completed immediately—do not delay for MRI unless NCCT is unavailable 1.

Critical Imaging Protocol

1. NCCT first (radiation dose ~3 mSv, acceptable and time-efficient) 1
2. CT angiography (CTA) to identify vessel occlusion location—determines if large vessel occlusion (LVO) is present 1
3. Do NOT delay thrombolysis for perfusion imaging if patient meets clinical criteria 2

Ischemic Stroke Subtype: Thrombotic vs Embolic

CTA identifies the occlusion site which guides mechanism determination:

• Large vessel occlusions (LVO): Intracranial carotid artery, M1 occlusions—typically embolic, less likely to recanalize with thrombolytics alone, require endovascular thrombectomy (EVT) consideration 1
• Distal occlusions: Higher probability of recanalization with thrombolytics, though EVT increasingly performed 1
• Multiphase CTA provides additional hemodynamic information with same contrast bolus 1

Tenecteplase Dosing: Latest Evidence

Primary Recommendation: Tenecteplase 0.25 mg/kg IV bolus (maximum 25 mg) is now the preferred thrombolytic for acute ischemic stroke within 4.5 hours 3, 4, 5.

Key advantages over alteplase:

• Single IV bolus vs 1-hour infusion 2
• Superior recanalization in LVO 3, 4
• Improved excellent functional outcome (mRS 0-1) at 90 days 4
• Similar safety profile (no increased symptomatic ICH or mortality) 3, 4
• Significant cost savings (>$40,000 documented in recent implementation) 6

Specific Clinical Scenarios

For LVO within 4.5 hours:

• Tenecteplase 0.25 mg/kg is strongly recommended over alteplase (moderate evidence, strong recommendation) 3
• Provides better recanalization rates and functional outcomes 3, 4

For minor stroke (low NIHSS) without major intracranial occlusion:

• Tenecteplase 0.25 mg/kg may be considered as alternative to alteplase 2

DO NOT use tenecteplase 0.40 mg/kg:

• Strong recommendation against this dose (failed to show superiority, no additional benefit) 2, 3

Extended window (4.5-24 hours):

• Tenecteplase 0.25 mg/kg improves outcomes when EVT is unavailable 7
• In EVT-capable centers, benefit is primarily improved recanalization 7
• Requires advanced imaging (CTP or DW-MRI) for patient selection 2

Wake-up stroke or unknown onset:

• Do NOT use tenecteplase 0.25 mg/kg with non-contrast CT alone (strong recommendation against) 3
• May be reasonable alternative to alteplase if selected with advanced imaging (perfusion or DW-MRI) 3

Treatment Algorithm

Within 4.5 Hours of Symptom Onset:

1. NCCT immediately → Exclude hemorrhage
2. CTA → Identify vessel occlusion
3. Tenecteplase 0.25 mg/kg IV bolus (preferred) OR alteplase 0.9 mg/kg (10% bolus, 90% over 60 min) 2, 3, 5
4. If LVO present → Proceed directly to EVT without waiting for thrombolytic response 2
5. Blood pressure control → Must be <185/110 mmHg before thrombolysis 2

Beyond 4.5 Hours (up to 24 hours):

1. Advanced imaging required (CTP or DW-MRI) 2
2. If EVT unavailable → Tenecteplase 0.25 mg/kg provides significant benefit 7
3. If EVT available → Tenecteplase improves recanalization but functional benefit less clear 7

Critical Safety Points

Contraindications remain similar to alteplase 2:

• Active intracranial hemorrhage on NCCT
• Blood pressure >185/110 mmHg despite treatment
• Recent major surgery/trauma (timing individualized)

Avoid antiplatelet/anticoagulation for 24 hours post-thrombolysis unless compelling indication where benefit outweighs risk 2

Symptomatic ICH rates are equivalent between tenecteplase 0.25 mg/kg and alteplase (~2-6%) 3, 4, 8

DOAC patients: Recent data suggest tenecteplase has similar safety to alteplase in patients with recent DOAC use, though guidelines still recommend caution 8

Common Pitfalls to Avoid

• Do not delay thrombolysis for perfusion imaging in the <4.5 hour window 2
• Do not use tenecteplase 0.40 mg/kg dose—no benefit, potential harm 3
• Do not skip thrombolysis in LVO patients even if going directly to EVT—give tenecteplase first 2, 3
• Do not use tenecteplase for wake-up stroke without advanced imaging 3
• Do not wait to assess clinical response to thrombolysis before proceeding to EVT in LVO 2

The 2026 AHA/ASA guidelines 5 and 2023 European Stroke Organisation recommendations 3 now support transitioning to tenecteplase 0.25 mg/kg as the preferred thrombolytic based on superior efficacy data, equivalent safety, and practical advantages.