The administration of intravenous tissue Plasminogen Activator (IV tPA), such as Alteplase or the increasingly utilized Tenecteplase, is a highly time-sensitive “level one” recommendation for acute ischemic stroke (AIS). However, because tPA works by dissolving clots systemically, it carries a significant risk of life-threatening hemorrhage.

The 2026 AHA/ASA Guidelines have recently updated the eligibility framework, shifting several previous “absolute” contraindications into “relative” categories to expand access to life-saving treatment.

1. Core Inclusion Criteria

Before assessing contraindications, a patient must meet the following baseline requirements:

• Diagnosis: Clinical diagnosis of ischemic stroke causing a measurable neurological deficit.
• Age: $\ge 18$ years (new 2026 guidance now also provides specific pathways for pediatric patients aged 28 days to 18 years).
• Time Window: Treatment can be initiated within 4.5 hours of “Last Known Well” (LKW).
  • Update: Patients with “Wake-up Stroke” or unknown onset may now be eligible up to 24 hours if advanced imaging (CT Perfusion or MRI) shows salvageable brain tissue (mismatch).

2. Absolute Contraindications (The “Never” List)

If any of these are present, the risk of fatal bleeding generally outweighs the benefit of tPA.

Clinical History & Imaging

• Evidence of Intracranial Hemorrhage (ICH): Any blood on the initial non-contrast CT.
• Subarachnoid Hemorrhage: Clinical suspicion (e.g., “thunderclap headache”) even if the CT is negative.
• Recent Events: Ischemic stroke, severe head trauma, or intracranial/intraspinal surgery within the last 3 months.
• Structural Abnormalities: Known intracranial neoplasm, arteriovenous malformation (AVM), or aneurysm.
• Aortic Dissection: Suspected or confirmed aortic arch dissection.

Hematologic & Laboratory

• Active Internal Bleeding: Current gastrointestinal or urinary tract hemorrhage.
• Platelet Count: $< 100,000/mm^3$.
• Coagulopathy: * INR $> 1.7$.
  • PT $> 15$ seconds.
  • aPTT elevated above the normal range due to recent heparin use (within 48 hours).
• DOAC Usage: Use of Direct Oral Anticoagulants (e.g., Apixaban, Rivaroxaban) within the last 48 hours, unless specific lab tests (anti-Xa activity) are normal.

3. Relative Contraindications (The “Expert Consultation” List)

These factors require a nuanced risk-benefit analysis, often involving a neurology consult.

• Blood Pressure: SBP $> 185$ mmHg or DBP $> 110$ mmHg.Note: If BP can be lowered safely with antihypertensives (e.g., Labetalol or Nicardipine) to below $185/110$ and maintained, the patient can receive tPA.
• Pregnancy: tPA can be considered if the benefits of treating a severe stroke outweigh the risk of uterine bleeding.
• Major Surgery/Trauma: Within the previous 14 days.
• Glucose: $< 50$ mg/dL (2.8 mmol/L). Hypoglycemia can mimic stroke; if symptoms persist after normalizing glucose, tPA may proceed.
• Seizure at Onset: Only a contraindication if the clinician believes the deficits are “post-ictal” (Todd’s paralysis) rather than a true stroke.

4. Notable Updates in 2026 Guidelines

1. Tenecteplase (TNK): Now officially endorsed as a single-bolus alternative to Alteplase, simplifying administration in busy Emergency Departments.
2. Extended Window: The move toward “Tissue over Time” means that a strict 4.5-hour cutoff is no longer the sole rule for patients with access to advanced perfusion imaging.
3. Mild Strokes: If the stroke symptoms are “disabling” (e.g., loss of vision, aphasia, or inability to walk), tPA is recommended even if the NIHSS score is very low (e.g., 1 or 2).

5. References & Resources

Primary Guidelines

• AHA/ASA 2026: 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke
• AHA/ASA 2019 (Previous): 2019 Update to the 2018 AIS Guidelines

Decision Tools

• MDCalc: tPA Contraindications Checklist
• NIH Stroke Scale (NIHSS): Official Training & Score Calculation