(COR IIb; LOE C-LD) The safety and efficacy of IV alteplase in the early postpartum period (<14 d after delivery) have not been well established. (COR IIb; LOE C-LD) Ophthalmological conditions Use of IV alteplase in patients presenting with AIS who have a history of diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions is reasonable to recommend, but the potential increased risk of visual loss should be weighed against the anticipated benefits of reduced stroke-related neurological deficits. (COR IIa; LOE B-NR) Sickle cell disease IV alteplase for adults presenting with an AIS with known sickle cell disease can be beneficial. (COR IIa; LOE B-NR) Hyperdense MCA sign In patients with a hyperdense MCA sign, IV alteplase can be beneficial. (COR IIa; LOE B-NR) Illicit drug use Treating clinicians should be aware that illicit drug use may be a contributing factor to incident stroke. IV alteplase is reasonable in instances of illicit drug use associated AIS in patients with no other exclusions. (COR IIa; LOE C-LD) Stroke mimics The risk of symptomatic intracranial hemorrhage in the stroke mimic population is quite low; thus, starting IV alteplase is probably recommended in preference over delaying treatment to pursue additional diagnostic studies. (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. 