A 58-year-old man presents to the emergency department 2 hours after onset of acute ischemic stroke with NIHSS score of 18. CT head excludes hemorrhage. What is the drug of choice for immediate thrombolytic therapy?

Explanation

## First-Line Thrombolytic Agent in Acute Ischemic Stroke **Key Point:** Alteplase (rt-PA) is the only FDA-approved and guideline-recommended thrombolytic agent for acute ischemic stroke within the 4.5-hour window. ### Mechanism & Rationale Alteplase is a recombinant tissue plasminogen activator that: - Selectively activates fibrin-bound plasminogen - Achieves rapid thrombus dissolution - Has the most robust evidence base from the NINDS rt-PA Stroke Study (1995) and subsequent trials (IST-3, ECASS-3) - Demonstrates significant reduction in disability at 3 months when given within 4.5 hours of symptom onset ### Dosing in Acute Stroke **Standard regimen:** - **0.9 mg/kg** (maximum dose 90 mg) - 10% of dose as intravenous bolus over 1 minute - Remaining 90% as intravenous infusion over 60 minutes ### Inclusion & Exclusion Criteria Summary | Criterion | Requirement | |-----------|-------------| | **Time window** | ≤4.5 hours from symptom onset (or last known well) | | **CT/MRI** | Must exclude intracranial hemorrhage | | **Blood glucose** | 50–400 mg/dL | | **Platelet count** | ≥100,000/μL | | **INR** | <1.7 (if on warfarin) | | **Recent surgery** | Avoid if within 3 months | | **Recent thrombolysis** | Avoid if within 3 months | **High-Yield:** The **4.5-hour window** is critical; beyond this, risk of hemorrhagic transformation outweighs benefit except in select cases (e.g., wake-up stroke with diffusion-perfusion mismatch on MRI). **Clinical Pearl:** In patients with contraindications to IV thrombolysis or beyond the IV window, **mechanical thrombectomy** (endovascular intervention) is the preferred option if within 24 hours of symptom onset and imaging criteria are met. ### Why Alteplase Over Other Thrombolytics - **Streptokinase & Urokinase:** Systemic fibrinolytic agents; higher risk of hemorrhagic complications and not approved for acute stroke - **Tenecteplase:** TNK-tPA is a newer agent with longer half-life and better fibrin specificity, but it is NOT yet standard of care in most countries for acute stroke (though trials are ongoing); alteplase remains the gold standard [cite:Harrison 21e Ch 445]