Thrombolysis in Ischemic Stroke - Current Guidelines (2026)

1. Thrombolytic Agents

Alteplase (rtPA) - Standard Agent

• Dose: 0.9 mg/kg IV (maximum 90 mg) over 60 minutes; 10% of the dose given as a bolus over the first minute
• Approved by FDA for ischemic stroke

Tenecteplase - Now Guideline-Endorsed

• Dose: 0.25 mg/kg single IV bolus (maximum 25 mg)
• The 2026 AHA/ASA guideline endorses tenecteplase as equivalent to alteplase within 4.5 hours - a major update from prior guidance
• Advantages: single bolus (vs. 60-minute infusion for alteplase), easier to administer, especially for pre-thrombectomy bridging
• FDA approved in the US as of 2024; approved across most European countries 2024-2025
• Particularly preferred in patients with large vessel occlusion going for mechanical thrombectomy

2. Time Windows

• Benefit declines with time: odds ratio for favorable 3-month outcome is 2.55 for treatment at 0-90 min, 1.64 at 91-180 min, and 1.26 at 181-270 min (Goldman-Cecil Medicine)

3. Time Goals (Door-to-Needle)

4. Inclusion Criteria (0-3 hours)

• Diagnosis of ischemic stroke with measurable neurologic deficit
• Symptom onset < 3 hours before treatment
• Age ≥ 18 years

5. Exclusion Criteria (Contraindications)

Absolute (0-3 hours window)

• Significant head trauma or prior stroke in previous 3 months
• Symptoms suggesting subarachnoid hemorrhage
• Arterial puncture at noncompressible site within 7 days
• History of prior intracranial hemorrhage
• Intracranial neoplasm, AVM, or aneurysm
• Recent intracranial or intraspinal surgery
• Elevated BP: systolic >185 mmHg or diastolic >110 mmHg (that cannot be controlled)
• Active internal bleeding
• Acute bleeding diathesis, including platelet count < 100,000/mm³
• Heparin received within 48 hours with elevated aPTT
• Current anticoagulant use with INR > 1.7 or PT > 15 seconds
• Blood glucose < 50 mg/dL or > 400 mg/dL

Additional Relative Contraindications (3-4.5 hour window)

• Age > 80 years (not absolute; individualized decision per 2026 guideline)
• Severe stroke (NIHSS > 25)
• Combination of prior stroke AND diabetes mellitus
• Any prior anticoagulant use (even with normal INR)

2026 update: The guideline has modified and liberalized several contraindications - many formerly absolute exclusions (e.g., recent myocardial infarction, mild/improving strokes, prior use of DOACs) are now treated as individual risk-benefit decisions rather than hard stops.

6. Anticoagulant Considerations

• Warfarin: Safe to give rtPA if INR ≤ 1.7; contraindicated if INR > 1.7
• DOACs (direct thrombin inhibitors / direct factor Xa inhibitors): Normal prothrombin time does NOT rule out anticoagulant effect - appropriate specific assays (anti-Xa level, thrombin time/ECT for dabigatran) must be normal before giving rtPA
• Post-thrombolysis, anticoagulants and antiplatelet agents should not be started for 24 hours; obtain follow-up CT/MRI first

7. Post-Thrombolysis Monitoring

• ICU or stroke unit admission
• BP and neuro checks every 15 min during infusion and for 2 hours after, then every 30 min for 6 hours, then hourly until 24 hours
• Maintain BP ≤ 180/105 mmHg
• Discontinue infusion immediately and obtain emergency CT if: severe headache, acute hypertension, nausea/vomiting, or neurologic deterioration (suspect intracranial hemorrhage)
• Delay NGT, bladder catheters, and arterial lines if not immediately essential

8. Thrombolysis + Endovascular Thrombectomy (Bridge Therapy)

• For large vessel occlusion (LVO): IV thrombolysis followed by or concurrent with mechanical thrombectomy
• Tenecteplase (single bolus) is preferred as bridge therapy due to easier logistics
• Thrombectomy extends up to 6 hours (standard), and up to 24 hours if imaging shows ischemic penumbra (DAWN/DEFUSE criteria)
• Intra-arterial thrombolysis as rescue therapy after incomplete thrombectomy reperfusion is emerging, with recent 2025 meta-analysis (PMID 40745037) showing benefit

9. Pediatric Stroke (New in 2026 Guideline)

• First-ever detailed pediatric recommendations
• IV alteplase may be considered within 4.5 hours for children aged 28 days to 18 years with disabling deficits
• Mechanical thrombectomy may be effective for LVO in children ≥ 6 years within 6 hours, and reasonable up to 24 hours if imaging shows salvageable tissue

10. Key 2026 Updates at a Glance

• Goldman-Cecil Medicine, Table 376-6 to 376-8 (IV rtPA protocol and contraindications)
• Bradley and Daroff's Neurology in Clinical Practice (intraarterial thrombolysis)
• 2026 AHA/ASA Stroke Guideline (PMID 41582814) - Prabhakaran S et al., Stroke 2026
• Tenecteplase meta-analysis: Wu N et al., J Neurol 2024 (PMID 38782799)
• Extended thrombolysis Bayesian meta-analysis: Garg R & Brophy JM, Am J Emerg Med 2026 (PMID 41529589)