In the extended 3-4.5-hour window, exercise heightened caution in individuals over 80-85, those with NIHSS above 25, limited life expectancy, or significant comorbidities. Severe hepatic or renal disease increases bleeding risk due to hemostatic impairment. Intracranial tumors require case-by-case assessment of hemorrhage risk before proceeding.

Relative contraindications include minor/improving symptoms, recent major surgery, GI/GU bleeding within 3 weeks, recent lumbar puncture, post-MI pericarditis, glucose below 50 or above 400, and seizure at onset.In the 3-4.5-hour window, additional caution applies for age over 80-85, NIHSS above 25, limited life expectancy, and significant comorbidities.Pregnancy, left ventricular thrombus, and septic thrombophlebitis require careful clinical judgment.Symptoms are considered too mild if the individual is expected to go home without rehabilitation or significant residual deficit.Severe hepatic or renal disease increases bleeding risk via hemostatic impairment.Tenecteplase is the newer thrombolytic agent for acute ischemic stroke.