(COR III: Harm; LOE C-EO) (Recommendation wording modified to match COR III stratifications.) Intracranial/intraspinal surgery within 3 mo For patients with AIS and a history of intracranial/spinal surgery within the prior 3 mo, IV alteplase is potentially harmful. (COR III: Harm; LOE C-EO) History of intracranial hemorrhage IV alteplase administration in patients who have a history of intracranial hemorrhage is potentially harmful. (COR III: Harm; LOE C-EO) Subarachnoid hemorrhage IV alteplase is contraindicated in patients presenting with symptoms and signs most consistent with an SAH. (COR III: Harm; LOE C-EO) GI malignancy or GI bleed within Patients with a structural GI malignancy or recent bleeding event within 21 d of their stroke event should be considered high risk, and IV alteplase administration is potentially harmful. (COR III: Harm; LOE C-EO) Coagulopathy The safety and efficacy of IV alteplase for acute stroke patients with platelets <100000/mm3 , INR >1.7, aPTT >40 s, or PT >15 s are unknown, and IV alteplase should not be administered. (COR III: Harm; LOE C-EO) (In patients without history of thrombocytopenia, treatment with IV alteplase can be initiated before availability of platelet count but should be discontinued if platelet count is <100000/mm3 . In patients without recent use of OACs or heparin, treatment with IV alteplase can be initiated before availability of coagulation test results but should be discontinued if INR is >1.7 or PT is abnormally elevated by local laboratory standards.) (Recommendation wording modified to match COR III stratifications.) LMWH IV alteplase should not be administered to patients who have received a full treatment dose of LMWH within the previous 24 h. (COR III: Harm; LOE B-NR) (Recommendation wording modified to match COR III stratifications.) 