Intravenous thrombolysis remains the foundation of acute ischemic stroke reperfusion, and for patients without large-vessel occlusion it is often the only reperfusion therapy available. The therapeutic case rests on a simple, time-dependent biology: dissolving the occluding clot restores flow to threatened but not-yet-infarcted brain, and the benefit shrinks with every minute of delay. The original NINDS trial established that alteplase given within 3 hours improved the odds of minimal or no disability at 90 days, despite a higher rate of symptomatic hemorrhage.1 This page summarizes contemporary eligibility windows, dosing, and the screening that protects patients from avoidable harm. It is educational only; institutional protocols and national guidelines differ, and every decision should be made against your local pathway.

Time windows: the standard 4.5 hours and beyond

The workhorse window is ischemic stroke within 4.5 hours of last known well. The 3-to-4.5-hour extension rests on ECASS III, which showed alteplase improved functional outcome in that later band, again at the cost of more symptomatic hemorrhage but without an increase in mortality.2 Beyond 4.5 hours, eligibility shifts from the clock to the tissue. WAKE-UP used a DWI–FLAIR mismatch — a lesion bright on diffusion but not yet visible on FLAIR — as a surrogate for a recent onset, and showed benefit from alteplase in patients with unwitnessed or wake-up stroke.3 EXTEND extended thrombolysis to roughly 9 hours from onset (or the midpoint of sleep) in patients selected by automated perfusion imaging showing salvageable penumbra, again improving functional outcomes.4

Bedside pearl

For wake-up and unwitnessed strokes, do not default to exclusion. A DWI–FLAIR mismatch or a favorable perfusion mismatch can make an apparently out-of-window patient a candidate. Anchor on last known well, not on the time symptoms were discovered.

Agent and dosing: tenecteplase versus alteplase

Two agents dominate practice. Tenecteplase is given as a single 0.25 mg/kg IV bolus (maximum 25 mg) and is increasingly the agent of choice; the AcT trial demonstrated non-inferiority to alteplase for functional outcome with a comparable safety profile, and its single-bolus administration simplifies workflow and transfer.5 Alteplase, the long-standing standard, is dosed at 0.9 mg/kg IV (maximum 90 mg), given as a 10% bolus followed by the remaining 90% infused over 60 minutes.1 Whichever agent your institution uses, weight-based dosing and the per-agent maximum dose are easy to get wrong under time pressure — confirm both before the bolus.

  • Tenecteplase — 0.25 mg/kg IV bolus, maximum 25 mg, single push.
  • Alteplase — 0.9 mg/kg IV, maximum 90 mg; 10% as a bolus, then 90% over 60 minutes.
  • Use an accurate or carefully estimated weight; do not improvise a dose from a guessed weight when a stated weight is available.

Absolute exclusions and the pre-bolus checklist

Before any bolus, several findings are hard stops. Intracranial hemorrhage on imaging excludes thrombolysis outright. Blood pressure that cannot be brought and kept below 185/110 mmHg before treatment is a contraindication until it is controlled. Active internal bleeding, recent intracranial or intraspinal surgery, recent serious head trauma, and a history of prior intracranial hemorrhage are also absolute exclusions. The anticoagulation history is decisive: an INR above 1.7, therapeutic low-molecular-weight heparin within the preceding 24 hours, or a direct oral anticoagulant within roughly 48 hours without reversal all preclude treatment in standard protocols.

  • Intracranial hemorrhage on imaging.
  • Blood pressure not reducible below 185/110 mmHg before treatment.
  • Active internal bleeding.
  • Recent intracranial or intraspinal surgery, serious head trauma, or prior intracranial hemorrhage.
  • INR >1.7, therapeutic LMWH within 24 hours, or a DOAC within ∼48 hours without reversal.

Pitfall

Do not give the bolus before blood pressure is controlled. A pressure that cannot be brought below 185/110 mmHg is a contraindication, not a hurdle to push past — treating into uncontrolled hypertension raises the risk of symptomatic hemorrhage. Stabilize first, then treat.

Stroke mimics and the seizure trap

Two metabolic states deserve a deliberate check because they mimic stroke and are reversible: glucose below 50 mg/dL or above 400 mg/dL can produce focal deficits that resolve with correction, so confirm and treat the glucose before committing to thrombolysis. Seizure at onset is a classic point of confusion. A post-ictal Todd paresis can masquerade as a vascular deficit, but a seizure at onset is not an absolute exclusion if the residual deficit is clearly attributable to an ischemic event rather than the seizure itself. When the picture is ambiguous, advanced imaging showing a corresponding perfusion or diffusion lesion helps distinguish a true infarct from a post-ictal phenomenon.

Where guidelines and institutions diverge

The points above represent widely held practice, but the field is not uniform. Tenecteplase has become the preferred agent in many centers while others retain alteplase; extended-window and wake-up protocols depend on local access to automated perfusion software and MRI; and the precise handling of relative contraindications — recent surgery, mild or rapidly improving deficits, advanced age, and anticoagulant timing — varies by guideline version and institution. Treat this page as a framework, not a protocol, and defer to your own stroke service and current national guidance for individual patients.