Who is eligible for tissue plasminogen activator (tPA)?

Eligibility for Tissue Plasminogen Activator (tPA) in Acute Ischemic Stroke

IV tPA should be offered to acute ischemic stroke patients who meet National Institute of Neurological Disorders and Stroke (NINDS) inclusion/exclusion criteria and can be treated within 3 hours after symptom onset, and should be considered in patients who meet European Cooperative Acute Stroke Study (ECASS) III criteria for treatment between 3 to 4.5 hours after symptom onset. 1

Time Windows for tPA Administration

• IV tPA is strongly recommended for patients who can receive treatment within 3 hours of stroke symptom onset 1
• IV tPA should be considered for eligible patients between 3-4.5 hours after stroke symptom onset 1, 2
• Treatment should be initiated as rapidly as possible after patient arrival and CT scan, with a target door-to-needle time of less than 60 minutes in 90% of treated patients and a median door-to-needle time of 30 minutes 1

Inclusion Criteria for tPA Administration

• Adult patients with clinical diagnosis of acute ischemic stroke 1
• Measurable neurological deficit 1
• Time of symptom onset clearly determined 1
• CT scan showing no evidence of intracranial hemorrhage 1, 2
• For patients in the 3-4.5 hour window, additional ECASS III criteria must be met 1

Exclusion Criteria for tPA Administration

• Evidence of intracranial hemorrhage on pre-treatment imaging 2
• Clinical presentation suggestive of subarachnoid hemorrhage 1
• Active internal bleeding or bleeding diathesis 1
• Recent intracranial or intraspinal surgery, serious head trauma, or previous stroke 1
• Uncontrolled hypertension (systolic >185 mmHg or diastolic >110 mmHg) 1
• Seizure at the onset of stroke with postictal residual neurological impairments 1
• Current use of direct oral anticoagulants (DOACs) without validated assessment of drug levels 1

Special Considerations

• Patients with severe neurological deficits (high NIHSS scores) may still benefit from tPA despite higher risk of intracerebral hemorrhage 3
• Patients with evidence of early ischemic changes on CT (brain edema or mass effect) can still be considered for tPA, though they have higher hemorrhagic risk 3
• For patients with brain CT scans showing early signs of more extensive infarction (ASPECTS score <6), the decision to treat should be based on clinical judgment 1
• Patients with mild or rapidly improving symptoms should still be carefully evaluated for tPA, as some may have poor outcomes without treatment 4
• Hospital inpatients who develop sudden stroke symptoms should be rapidly evaluated and considered for appropriate acute stroke treatments 1

Dosing and Administration

• tPA should be administered at a dose of 0.9 mg/kg to a maximum of 90 mg total dose 1
• 10% (0.09 mg/kg) given as an intravenous bolus over one minute 1
• Remaining 90% (0.81 mg/kg) given as an intravenous infusion over 60 minutes 1

Management of Complications

• For tPA-induced angioedema: discontinue the tPA infusion if still running, obtain airway management assistance if required, and administer intravenous hydrocortisone 100 mg, diphenhydramine 50 mg, and ranitidine 50 mg 1
• There is insufficient evidence to support routine use of fresh frozen plasma, prothrombin complex concentrates, or platelet transfusions for tPA-associated bleeding 1

Endovascular Therapy Considerations

• Eligible patients who can be treated within six hours of symptom onset should be considered for endovascular therapy, particularly those with proximal occlusion in the anterior circulation 1
• Endovascular therapy is indicated in patients who have received IV tPA and those who are not eligible for IV tPA 1
• Patients on DOACs who are not eligible for IV tPA may be considered for endovascular therapy 1

Common Pitfalls in tPA Administration

• Undertreating certain groups including older patients, patients with milder strokes, women, and minorities 5
• Incorrectly excluding patients with mild or improving symptoms who may still benefit from treatment 4
• Delaying treatment due to unnecessary tests or procedures 1
• Failing to recognize that the effectiveness of tPA is time-dependent, with greater benefits observed with earlier treatment 1