(COR IIa; LOE B-NR) Contraindications (COR III: No Benefit) And (COR III: Harm) nondisabling stroke For otherwise eligible patients with mild nondisabling stroke (NIHSS score 0 5), IV alteplase is not recommended for patients who could be treated within 3 h of ischemic stroke symptom onset or patient last known well or at baseline state. (COR III: No Benefit, LOE B-R) nondisabling stroke For otherwise eligible patients with mild nondisabling stroke (NIHSS score 0 5), IV alteplase is not recommended for patients who could be treated within 3 and 4.5 h of ischemic stroke symptom onset or patient last known well or at baseline state. (COR III: No Benefit, LOE C-LD) CT There remains insufficient evidence to identify a threshold of hypoattenuation severity or extent that affects treatment response to alteplase. However, administering IV alteplase to patients whose CT brain imaging exhibits extensive regions of clear hypoattenuation is not recommended. These patients have a poor prognosis despite IV alteplase, and severe hypoattenuation defined as obvious hypodensity represents irreversible injury. (COR III: No Benefit; LOE A) ICH IV alteplase should not be administered to a patient whose CT reveals an acute intracranial hemorrhage. (COR III: Harm; LOE C-EO) Ischemic stroke within 3 mo Use of IV alteplase in patients presenting with AIS who have had a prior ischemic stroke within 3 mo may be harmful. (COR III: Harm; LOE B-NR) Severe head trauma within 3 mo In AIS patients with recent severe head trauma (within 3 mo), IV alteplase is contraindicated. (COR III: Harm; LOE C-EO) Acute head trauma Given the possibility of bleeding complications from the underlying severe head trauma, IV alteplase should not be administered in posttraumatic infarction that occurs during the acute in-hospital phase. (COR III: Harm; LOE C-EO) (Recommendation wording modified to match COR III stratifications.) 