What are the indications, contraindications, and recommended dosing and administration guidelines for alteplase (recombinant tissue‑type plasminogen activator) in adult patients with acute ischemic stroke?

Alteplase in Acute Ischemic Stroke

Dosing and Administration

Administer intravenous alteplase at 0.9 mg/kg (maximum 90 mg total) with 10% given as an IV bolus over exactly 1 minute, followed by the remaining 90% infused over 60 minutes. 1, 2

• This is the only FDA-approved thrombolytic regimen for acute ischemic stroke; never use the myocardial infarction dosing protocol. 2
• The dose does not require adjustment based on age, stroke severity (NIHSS score), or presence of comorbidities. 1, 2

Time Windows and Eligibility Criteria

0–3 Hour Window (Broadest Eligibility)

All patients presenting within 3 hours of symptom onset should receive alteplase if they meet basic eligibility criteria, regardless of age >80 years, stroke severity (including NIHSS >25), or concurrent single or dual antiplatelet therapy. 1, 2

• Treatment within this window provides a 12% absolute increase in achieving minimal or no disability (39% vs 26% with placebo), yielding a number-needed-to-treat of 8.3. 2
• Each 15-minute delay in treatment exponentially reduces the probability of a favorable outcome—"time is brain." 1, 2
• Patients treated within 1.5 hours have 2.81 times higher odds of achieving a favorable outcome compared to placebo (95% CI 1.75–4.50). 2

3–4.5 Hour Extended Window (ECASS III Criteria)

Alteplase may be administered between 3 and 4.5 hours after symptom onset in patients who satisfy ECASS III criteria, providing an odds ratio of 1.40 for favorable outcome versus placebo (95% CI 1.05–1.85). 1, 3

Four additional exclusion criteria apply in the 3–4.5 hour window: 1, 2

• Age >80 years
• Any oral anticoagulant use (regardless of INR)
• NIHSS >25
• Combined history of diabetes and prior ischemic stroke

Beyond 4.5 Hours

The 2026 AHA/ASA guidelines give a Grade 1B recommendation against routine IV alteplase after 4.5 hours from symptom onset. 2

• However, the 2025 HOPE trial demonstrated that in highly selected patients with salvageable brain tissue identified by perfusion imaging (4.5–24 hours after onset), alteplase increased functional independence (40% vs 26%; adjusted RR 1.52,95% CI 1.14–2.02), despite higher symptomatic intracranial hemorrhage (3.8% vs 0.51%). 4
• This extended-window approach requires advanced perfusion imaging (CT perfusion or DWI-MRI) and should only be considered when salvageable tissue is documented. 4

Mandatory Pre-Treatment Requirements

Neuroimaging

Perform an immediate non-contrast head CT to exclude intracranial hemorrhage and assess early ischemic changes; this is the only mandatory imaging before alteplase. 1, 2

• Early ischemic changes involving ≤1/3 of the middle cerebral artery territory do not contraindicate treatment. 1
• Extensive hypoattenuation (obvious hypodensity representing irreversible injury) is an absolute contraindication. 1

Blood Pressure Management

Systolic/diastolic blood pressure must be lowered to <185/110 mmHg before initiating alteplase using antihypertensive agents, and blood pressure stability must be confirmed. 1, 2

• After infusion, maintain blood pressure <180/105 mmHg for the first 24 hours. 1, 2
• Labetalol or low-dose IV β-blockers are recommended for blood pressure control. 2

Laboratory Requirements

Verify capillary blood glucose >50 mg/dL (>2.7 mmol/L) at the bedside before treatment; this is the only laboratory test that must precede alteplase administration. 1, 2

• Do not delay alteplase for complete blood count, electrolytes, renal function, coagulation studies, or cardiac enzymes unless a coagulopathy is clinically suspected. 2
• Obtain these tests concurrently but proceed with treatment once glucose is confirmed. 2

Absolute Contraindications

The following are absolute contraindications to alteplase: 1, 2

• Intracranial hemorrhage on initial CT scan
• History of any prior intracranial hemorrhage
• Platelet count <100,000/mm³
• International Normalized Ratio >1.7
• Activated partial thromboplastin time >40 seconds
• Prior ischemic stroke within the preceding 3 months
• Severe head trauma within the preceding 3 months
• Intracranial or intraspinal surgery within the prior 3 months
• Unclear or unwitnessed symptom onset with last-known-well time exceeding the applicable window (>3 hours for 0–3 hour window, >4.5 hours for extended window)

Relative Contraindications (Case-by-Case Assessment)

The following factors require individualized risk-benefit assessment but are not absolute contraindications: 1, 5

• Warfarin use with INR ≤1.7 or PT <15 seconds (Class IIb)
• Seizure at stroke onset when residual deficits are clearly stroke-related (Class IIa)
• Initial glucose <50 mg/dL or >400 mg/dL, corrected before treatment (Class IIb)
• Lumbar puncture within the prior 7 days (Class IIb)
• Major non-head trauma within 14 days (Class IIb)
• Major surgery within 14 days (Class IIb)
• Menstruation without menorrhagia (Class IIa) or with menorrhagia but stable hemodynamics (Class IIb)
• Extracranial cervical arterial dissection (Class IIa)
• Early neurological improvement but residual moderate deficit (Class IIa)

Special Populations

Elderly Patients (Age >80 Years)

Age >80 years is not a contraindication in the 0–3 hour window; elderly patients derive similar benefit with comparable hemorrhage risk to younger patients. 1, 2

• Age >80 years becomes an exclusion criterion only in the 3–4.5 hour extended window. 1, 2

Severe Stroke (High NIHSS)

Severe stroke symptoms (NIHSS >20 or even >25) do not contraindicate alteplase within the 0–3 hour window; despite increased hemorrhagic transformation risk, there is proven net clinical benefit. 1, 2

• NIHSS >25 becomes an exclusion only in the 3–4.5 hour window. 1, 2

Antiplatelet Therapy

Current single-agent antiplatelet therapy (e.g., aspirin) or dual antiplatelet therapy (e.g., aspirin plus clopidogrel) does not contraindicate alteplase, as the benefit outweighs the possible increased risk of symptomatic intracranial hemorrhage. 1

End-Stage Renal Disease

Patients with end-stage renal disease on hemodialysis with normal activated partial thromboplastin time are eligible for alteplase. 1

Integration with Mechanical Thrombectomy

Administer IV alteplase even when the patient is being evaluated for or will undergo mechanical thrombectomy; do not delay thrombolysis for vascular imaging or thrombectomy assessment. 2, 6

• Do not wait to assess the response to IV alteplase before proceeding to catheter angiography for thrombectomy. 2, 6
• For patients with suspected large-vessel occlusion presenting within 6 hours, obtain CT angiography from the aortic arch to the vertex immediately after the non-contrast CT, but do not delay alteplase administration. 2, 6
• For anterior-circulation large-vessel occlusions presenting 6–24 hours after last known well, use advanced imaging (CT perfusion or DWI-MRI) to determine thrombectomy eligibility using DAWN or DEFUSE-3 criteria. 2, 6

Post-Treatment Management

Monitoring Protocol

Assess neurological status every 15 minutes during the infusion, every 30 minutes for the subsequent 6 hours, and then hourly until 24 hours post-treatment. 2

• If severe headache, acute hypertension, nausea, or vomiting occur, stop the infusion immediately and obtain an emergent CT scan. 2
• Monitor blood pressure every 15 minutes for the first 2 hours, every 30 minutes for the next 6 hours, and hourly thereafter up to 24 hours. 2

Antiplatelet Therapy

Delay aspirin and all other antiplatelet agents for at least 24 hours after alteplase administration. 2, 6

• Obtain a follow-up CT scan at 24 hours to exclude hemorrhagic transformation before starting any antiplatelet or anticoagulant therapy. 2
• Once imaging confirms no hemorrhage, initiate aspirin 160–325 mg within 24–48 hours of stroke onset. 2, 6

Anticoagulation

Avoid therapeutic anticoagulation for the first 24 hours after alteplase; aspirin is preferred over parenteral anticoagulants for acute stroke management. 2, 7

Procedural Delays

Delay placement of nasogastric tubes, indwelling bladder catheters, and intra-arterial pressure catheters until after the 24-hour monitoring period. 2

Hemorrhagic Complications

Symptomatic intracranial hemorrhage occurs in 2.4%–6.4% of patients treated with standard-dose alteplase, representing a number-needed-to-harm of approximately 17. 2, 7

• The absolute increase in symptomatic intracranial hemorrhage risk is approximately 6% (7% with thrombolysis vs 1% without). 7
• Baseline NIHSS >20 is a stronger predictor of symptomatic hemorrhage than age alone. 2
• Be aware of orolingual angioedema as a potential adverse effect that can cause partial airway obstruction, typically occurring within 30 minutes of infusion. 2, 7

Institutional Requirements for Optimal Outcomes

The effectiveness of alteplase is less well established in hospitals lacking an organized stroke system with 24/7 rapid CT access, dedicated stroke team, continuous neurological monitoring, blood-pressure management protocols, neurosurgical consultation, and a target door-to-needle time <60 minutes. 2, 8

Critical Pitfalls to Avoid

Do not withhold alteplase from patients >80 years old presenting within the 0–3 hour window; age is only an exclusion in the 3–4.5 hour window. 1, 2

Do not exclude patients with NIHSS >25 in the 0–3 hour window; severe stroke is not a contraindication when treatment is early. 1, 2

Do not wait for complete laboratory panels beyond bedside glucose before initiating alteplase; each minute of delay reduces the probability of a favorable outcome. 1, 2

Do not delay IV thrombolysis while obtaining CTA or assessing for mechanical thrombectomy eligibility; administer alteplase first. 2, 6

Do not obtain CT perfusion for patients presenting within 4.5 hours without large-vessel occlusion, as it adds no actionable information and only postpones definitive therapy. 2

Do not use the myocardial infarction alteplase dosing regimen (accelerated or front-loaded protocols); always use the stroke-specific 0.9 mg/kg protocol. 2

Do not wait to assess alteplase response before initiating thrombectomy evaluation; proceed directly to angiography when large-vessel occlusion is suspected. 2, 6