Table 3.

Indications and Contraindications of Intravenous Recombinant Tissue Plasminogen Activator.

Indications	Additional Recommendations	Contraindications
Mild disabling to severe stroke symptoms Symptom onset ≤ 4.5 h prior to treatment Age ≥ 18 years Blood pressure < 185/110 mm Hg Blood glucose > 50 mg/dL NCCT demonstrates early ischemic changes of mild to moderate extent other than frank hypodensity Prior antiplatelet therapy, either monotherapy or dual antiplatelet therapy End-stage renal disease; normal aPTT	Age > 80 years presenting in the 3- to 4.5-h window History of prior stroke and diabetes mellitus presenting in the 3- to 4.5-h window Mild disabling and severe (NIHSS > 25) stroke symptoms presenting in the 3- to 4.5-h window Wake-up and unknown time of onset with MRI-DWI lesion smaller than one-third of the MCA territory with no visible signal change on FLAIR Preexisting disability (mRS score ≥ 2) or dementia Early improvement of symptoms with persistent moderate impairment Seizure at onset and if residual impairments are secondary to stroke and not postictal changes Initial blood glucose < 50 or > 400 mg/dL that are normalized with persistent symptoms Coagulopathy—history of warfarin use with INR ≤ 1.7 or PT < 15 s Dural puncture Arterial puncture of a noncompressible blood vessel Recent major trauma within 14 days not involving the head Recent major surgery within 14 days Prior gastrointestinal and genitourinary bleeding Menstruation without a history of menorrhagia Extracranial cervical dissection Intracranial arterial dissection Small to moderate-sized unruptured and unsecured intracranial aneurysm (<10 mm) Intracranial vascular malformation Few cerebral microbleeds (≤10) Concomitant tirofiban, eptifibatide Extra-axial intracranial neoplasm Acute myocardial infarction Recent myocardial infarction within 3 months *** Acute pericarditis Left atrial or ventricular thrombus Other cardiac disease (e.g., cardiac myxoma, papillary fibroelastoma) Procedural stroke (e.g., cardiac or cerebral angiography) Systemic malignancy with >6-month life expectancy without other contraindications Pregnancy Ophthalmologic conditions Sickle cell disease Hyperdense MCA sign Illicit drug use Stroke mimics	Mild nondisabling stroke symptoms (NIHSS score 0–5) presenting within 4.5 h of symptom onset NCCT demonstrates extensive regions of clear hypoattenuation Intracranial hemorrhage Prior ischemic stroke within 3 months Severe head trauma within 3 months Acute head trauma Intracranial or intraspinal surgery within 3 months History of intracranial hemorrhage Symptoms and signs consistent with subarachnoid hemorrhage Structural gastrointestinal malignancy or recent bleeding within 21 days Coagulopathy * ○ Platelets < 100,000/mm3 ○ INR > 1.7 ○ aPTT > 40 s ○ PT > 15 s Treatment with full dose low molecular weight heparin within 24 h Treatment with thrombin inhibitors or factor Xa inhibitors within 48 h ** Concomitant abciximab Concomitant intravenous aspirin Infective endocarditis Aortic arch dissection Intra-axial intracranial neoplasm

Abbreviations: aPTT = activated partial thromboplastin time; DWI = diffusion weighted imaging; FLAIR = fluid attenuation imaging recovery; INR = international normalized ratio; IV TPA = intravenous recombinant tissue plasminogen activator; MCA = middle cerebral artery; MRI = magnetic resonance imaging; NCCT = non-contrast computed tomography; mRS = modified Rankin Scale; NIHSS = National Institutes of Health Stroke Scale; PT = prothrombin time; STEMI = ST-elevation myocardial infarction. * In patients without a history of thrombocytopenia, treatment with IV TPA can be initiated while awaiting the results of platelet count but should be discontinued if platelet count is <100,000/mm³. Similarly, in patients without recent use of oral anticoagulants or heparin, IV TPA can be initiated while awaiting the results of coagulation tests but should be discontinued if INR is >1.7 or PT is abnormally elevated as per the laboratory standards. ** IV TPA could be considered when coagulation tests (e.g., aPTT, INR, platelet count, ecarin clotting time, thrombin time, direct factor Xa activity assays) are normal or when the patient has not received a dose of an anticoagulant for >48 h with a normal renal function. *** Recent myocardial infarction within 3 months: reasonable to treat the ischemic stroke with IV TPA if the recent myocardial infarction was a non-STEMI, STEMI involving the right or inferior myocardium, or STEMI involving the left anterior myocardium.