A 58-year-old man with hypertension and diabetes presents to the emergency department 2 hours after onset of acute ischemic stroke confirmed on CT head. His NIHSS score is 8. What is the drug of choice for acute reperfusion therapy?

Explanation

## First-Line Thrombolytic Agent in Acute Ischemic Stroke **Key Point:** Alteplase (IV rTPA) is the only FDA-approved and guideline-recommended thrombolytic agent for acute ischemic stroke within the 3–4.5 hour window from symptom onset. ### Mechanism & Evidence Alteplase is a serine protease that converts plasminogen to plasmin, directly lysing fibrin-rich thrombi. The NINDS rt-PA Stroke Study (1995) demonstrated a 30% relative improvement in favorable neurological outcomes at 3 months when administered within 3 hours of symptom onset [cite:Harrison 21e Ch 445]. ### Dosing & Administration - **Total dose:** 0.9 mg/kg (maximum 90 mg) - **Bolus:** 10% of total dose IV over 1 minute - **Infusion:** Remaining 90% over 60 minutes - **Window:** Within 3 hours (standard) or 3–4.5 hours (selected patients without contraindications) ### Key Inclusion & Exclusion Criteria | Criterion | Requirement | |-----------|-------------| | **Time window** | < 3 hrs (or 3–4.5 hrs if eligible) | | **CT/MRI** | No intracranial hemorrhage | | **Blood glucose** | 50–400 mg/dL | | **Platelet count** | ≥ 100,000/μL | | **INR** | ≤ 1.7 (if on warfarin) | | **Recent surgery** | Avoid if < 3 months | | **Active bleeding** | Contraindicated | **Clinical Pearl:** Endovascular thrombectomy is now preferred over IV thrombolysis alone in patients with large vessel occlusion (LVO) in the anterior circulation, but IV alteplase should still be given if no contraindications, as it may improve outcomes before thrombectomy. **High-Yield:** The 3–4.5 hour window requires stricter criteria (age < 80, NIHSS ≤ 25, no diabetes history, no prior stroke) compared to the 0–3 hour window. **Mnemonic: THROMBOLYSIS** — Time-sensitive, Hemorrhage exclusion, Renal/coagulation status, Only within window, Myocardial infarction history, Blood pressure control, Only alteplase approved, Liver disease check, Young age preferred, Stroke type (ischemic only), Imaging mandatory, Seizure history, Start bolus then infusion.