Stroke: tPA Eligibility, Contraindications, Large Vessel Occlusion (LVO), & Thrombectomy

Stroke: tPA Eligibility, Contraindications, Large Vessel Occlusion (LVO), & Thrombectomy

A high-density, practical guide for clinicians and learners

What Is This?

This guide covers acute ischemic stroke (AIS) management, focusing on: - tPA (alteplase) eligibility & contraindications – The only FDA-approved IV thrombolytic for AIS. - Large vessel occlusion (LVO) – A severe stroke subtype caused by blockage in major cerebral arteries (e.g., MCA, ICA). - Mechanical thrombectomy – Endovascular clot retrieval for LVO, the gold standard for eligible patients.

Why use this today? Stroke is the 5th leading cause of death and a top cause of disability in the U.S. Rapid, evidence-based treatment saves lives and reduces long-term deficits. Missteps in eligibility or timing can mean the difference between recovery and permanent damage.

Why It Matters

• Time = Brain: Every minute of untreated LVO kills 1.9 million neurons.
• tPA works—but only if given correctly: Reduces disability by 30% if administered within 3–4.5 hours.
• Thrombectomy revolutionized stroke care: 50–60% of LVO patients achieve functional independence post-procedure (vs. ~30% with tPA alone).
• Missed contraindications = harm: tPA in the wrong patient can cause fatal intracranial hemorrhage (ICH).

Core Concepts

1. The "Time Window" & "Tissue Window"

• Time window: Strict clock-based eligibility (e.g., ?4.5 hours for tPA, ?24 hours for thrombectomy in select cases).
• Tissue window: Advanced imaging (CT perfusion, MRI) can identify salvageable brain tissue beyond time windows.
• Key concept: "Time is brain, but tissue is king." Some patients benefit from treatment even if outside traditional time limits.

2. tPA (Alteplase) – The "Clot-Busting" Drug

• Mechanism: Activates plasminogen-plasmin, which lyses fibrin clots.
• Dose: 0.9 mg/kg (max 90 mg), with 10% as bolus, remainder over 1 hour.
• Efficacy: NNT (Number Needed to Treat) = 8 for good outcome (vs. placebo).

3. Large Vessel Occlusion (LVO) – The "Big Clot" Problem

• Definition: Occlusion in proximal cerebral arteries (ICA, M1/M2 MCA, A1/A2 ACA, P1 PCA, basilar artery).
• Why it’s deadly:
• 80% of stroke-related deaths occur in LVO.
• Core infarct grows rapidly (1.9 mL/min in untreated LVO).
• Detection:
• Clinical: NIHSS ?6 (especially gaze deviation, aphasia, neglect, hemiplegia).
• Imaging: CTA (CT Angiography) or MRA (MR Angiography) to confirm LVO.

4. Mechanical Thrombectomy – "Fishing for Clots"

• Mechanism: Endovascular retrieval of clot using stent retrievers (e.g., Solitaire, Trevo) or aspiration catheters (e.g., Penumbra).
• Eligibility:
• LVO confirmed on CTA/MRA.
• ASPECTS ?6 (CT score assessing early ischemic changes; lower = worse prognosis).
• Time window: ?6 hours (standard), 6–24 hours (if imaging shows salvageable tissue).
• Efficacy: NNT = 2.6 for functional independence (vs. medical therapy alone).

How It Works: The Stroke Treatment Workflow

Step 1: Prehospital & ED Triage

• Goal: Door-to-needle ?45 min (tPA), door-to-puncture ?90 min (thrombectomy).
• Key actions:
• FAST exam (Face, Arm, Speech, Time).
• Last known well (LKW) time – Critical for eligibility.
• NIHSS (National Institutes of Health Stroke Scale) – Quantifies stroke severity (0–42; higher = worse).
• Blood glucose (hypoglycemia mimics stroke).
• Non-contrast CT (NCCT) – Rules out hemorrhage (tPA contraindication).

Step 2: tPA Eligibility & Contraindications

Inclusion Criteria (Must Meet All)

• Diagnosis of ischemic stroke (NCCT negative for hemorrhage).
• Measurable neurologic deficit (NIHSS ?1).
• Time from LKW:
• ?3 hours: Standard window.
• 3–4.5 hours: Extended window (with additional exclusions).
• Age ?18 years.

Absolute Contraindications (DO NOT GIVE tPA)

Relative Contraindications (Weigh Risks vs. Benefits)

• NIHSS >25 (severe stroke; high ICH risk).
• CT hypodensity >1/3 MCA territory (large infarct; high ICH risk).
• Recent MI (last 3 months).
• Pregnancy (rarely used; case-by-case).
• Seizure at onset (if stroke is cause of seizure).

Step 3: LVO Identification & Thrombectomy Workup

• If NIHSS ?6 + high suspicion for LVO-CTA head/neck (or MRA if contraindicated).
• If LVO confirmed:
• ASPECTS score (CT): ?6 = favorable; <6 = high ICH risk.
• CT perfusion (CTP) or MRI DWI/PWI (if time window unclear).
• Call neurointerventionalist (if thrombectomy-capable center).

Step 4: Thrombectomy Procedure

1. Femoral artery access-guide catheter to carotid/vertebral artery.
2. Microcatheter navigates to clot (using fluoroscopy).
3. Stent retriever deployed-clot trapped in stent.
4. Clot removed via aspiration or stent retrieval.
5. Post-procedure imaging (CT to rule out ICH).

Hands-On: Applying the Workflow

Prerequisites

• Knowledge:
• NIHSS scoring.
• CT interpretation (hemorrhage vs. ischemia).
• CTA basics (identifying LVO).
• Tools:
• Non-contrast CT (first-line imaging).
• CTA (for LVO detection).
• tPA dosing calculator (e.g., MDCalc).
• Thrombectomy-capable stroke center (if LVO suspected).

Step-by-Step Example: tPA Administration

Scenario: 65M presents with left hemiplegia, gaze deviation, aphasia (NIHSS = 18). LKW = 2 hours ago.

1. Assess ABCs (Airway, Breathing, Circulation).
2. Check glucose (120 mg/dL-normal).
3. Perform NIHSS (confirms severe stroke).
4. Non-contrast CT (no hemorrhage, no hypodensity >1/3 MCA).
5. Check BP (170/90-labetalol 10mg IV to lower to <185/110).
6. Confirm no contraindications (no recent surgery, INR 1.1, platelets 250k).
7. Calculate tPA dose:
8. Weight = 80 kg-0.9 mg/kg = 72 mg total.
9. Bolus = 7.2 mg (10%) over 1 min.
10. Infusion = 64.8 mg over 1 hour.
11. Monitor for ICH (neurologic checks q15min x 2h, then q30min x 6h).
12. Repeat CT at 24h (or if neurologic deterioration).

Expected outcome: If tPA works, NIHSS may improve within 1 hour. If not, CTA to assess for LVO.

Step-by-Step Example: Thrombectomy for LVO

Scenario: Same patient as above, but CTA shows right M1 MCA occlusion.

1. Confirm ASPECTS ?6 (CT shows early ischemic changes but no large infarct).
2. Activate neurointerventional team (door-to-puncture goal: ?90 min).
3. Transfer to angio suite (if not already at thrombectomy-capable center).
4. Procedure:
5. Femoral access-guide catheter to right ICA.
6. Microcatheter navigates to M1 clot.
7. Solitaire stent retriever deployed-clot trapped.
8. Clot removed via aspiration + stent retrieval.
9. Post-procedure:
10. CT to rule out ICH.
11. NIHSS reassessment (goal: improvement).
12. Admit to ICU (BP control, neurologic checks).

Expected outcome: 50–60% chance of functional independence (mRS 0–2 at 90 days).

Common Pitfalls & Mistakes

1. Missing the Time Window

• Mistake: Giving tPA at 4h 30min (outside 4.5h window) without advanced imaging.
• Fix: Use CT perfusion/MRI to assess salvageable tissue if 3–6h post-LKW.

2. Ignoring Relative Contraindications

• Mistake: Giving tPA to a patient with NIHSS 28 (high ICH risk) without considering thrombectomy.
• Fix: Thrombectomy is preferred for severe strokes (NIHSS >25) with LVO.

3. Delaying CTA for LVO

• Mistake: Waiting for MRI in a patient with NIHSS 12 + gaze deviation (high LVO suspicion).
• Fix: CTA first (faster, widely available). MRI if CTA contraindicated (e.g., renal failure).

4. Overlooking Blood Pressure Control

• Mistake: Giving tPA with BP 190/110 (increases ICH risk).
• Fix: Lower BP to <185/110 before tPA (labetalol, nicardipine).

5. Assuming All LVOs Are the Same

• Mistake: Treating a basilar artery occlusion the same as an MCA occlusion (basilar has higher mortality).
• Fix: Basilar occlusions are emergencies—thrombectomy even if >24h post-LKW in some cases.

Best Practices

For tPA Administration

Use a checklist (e.g., AHA tPA checklist) to avoid missed contraindications. ? Lower BP aggressively (goal <185/110) before tPA. ? Avoid antithrombotics for 24h post-tPA (increases ICH risk). ? Monitor for ICH (neurologic checks q15min x 2h, then q30min x 6h).

For LVO & Thrombectomy

NIHSS ?6 + cortical signs (aphasia, neglect, gaze deviation) = CTA. ? ASPECTS <6 = high ICH risk—consider medical management. ? Door-to-puncture ?90 min (every 30-min delay reduces good outcome by 10%). ? Use CT perfusion/MRI for late-window patients (DAWN/TRIAL criteria).

For Post-Procedure Care

BP control post-thrombectomy (goal <140/90 for 24h to reduce reperfusion injury). ? Repeat CT at 24h (or if neurologic deterioration). ? Early mobilization (if stable) to prevent complications (DVT, pneumonia).

Tools & Frameworks

Real-World Use Cases

1. The "Wake-Up Stroke" Patient

• Scenario: 72F found unresponsive at 7 AM (LKW unknown). NIHSS = 14. MRI shows DWI-FLAIR mismatch (salvageable tissue).
• Action:
• No tPA (time window unknown).
• CTA confirms LVO (M1 MCA).
• Thrombectomy performed at 9 AM (DAWN criteria met).
• Outcome: mRS 1 at 90 days (minimal disability).

2. The "tPA Failure" Case

• Scenario: 55M receives tPA for NIHSS 10 stroke (LKW 2h). No improvement at 1h. CTA shows ICA occlusion.
• Action:
• Transfer to thrombectomy center.
• Thrombectomy performed at 3h post-LKW.
• Outcome: Complete recanalization, NIHSS 2 at discharge.

3. The "Basilar Artery Occlusion" Emergency

• Scenario: 60M presents with locked-in syndrome (NIHSS 30). CTA shows basilar occlusion.
• Action:
• No tPA (NIHSS >25 = high ICH risk).
• Emergent thrombectomy (even at 12h post-LKW).
• Outcome: Survival with severe disability (mRS 4), but avoided death.

Check Your Understanding (MCQs)

Question 1

A 68-year-old man presents with left hemiplegia and aphasia (NIHSS = 16). Last known well was 3 hours ago. Non-contrast CT shows no hemorrhage. BP is 170/95. Next best step? A) Administer tPA immediately. B) Lower BP to <185/110, then give tPA. C) Order CTA to assess for LVO before tPA. D) Start aspirin and admit to stroke unit.

Correct Answer: B Explanation