Fibrinolytic Therapy

Pharmacology

Mechanism of Action: Alteplase and Tenecteplase are tissue plasminogen activators (tPA) that bind to fibrin within a thrombus and convert entrapped plasminogen to plasmin. This initiates local fibrinolysis and clot dissolution.

Quick Dose Calculator

kg

Acute Ischemic Stroke (AIS)

0 - 3 Hours
Standard FDA-approved window. Maximal clinical benefit.
3 - 4.5 Hours
Standard of care (Class 1).
Benefit outweighs risk even in elderly (>80y) or severe stroke (NIHSS >25).
Extended (4.5 - 9h)
Requires Advanced Imaging
DWI-FLAIR Mismatch:
Lesion visible on DWI (Ischemia) but NOT on FLAIR (Permanent damage) = Stroke is fresh (<4.5h).

Dosing Protocols Max dose applies to weight > 100kg

Agent Dose Max Administration Instructions
Tenecteplase 2026 Preferred 0.25 mg/kg 25 mg IV Bolus over 5 seconds.
Do not mix with dextrose. Flush line with NS before/after.
Alteplase 0.9 mg/kg 90 mg 1. Bolus: 10% of total dose IV over 1 min.
2. Infusion: 90% of total dose over 60 mins.

Contraindications

Absolute

  • Active internal bleeding or ICH history.
  • Stroke/Head trauma within 3 months.
  • Intracranial neoplasm, AVM, or aneurysm.
  • Symptoms suggestive of SAH.
  • BP > 185/110 mmHg (refractory).
  • Infective endocarditis.
  • Coagulopathy: Plt <100k, INR >1.7, DOAC use <48h, or therapeutic Heparin.

Relative

  • Minor/rapidly improving symptoms.
  • Pregnancy.
  • Major surgery/trauma < 14 days.
  • GI/GU hemorrhage < 21 days.
  • Seizure at onset with postictal deficit.
  • Recent arterial puncture (non-compressible).
Pre-Treatment BP Goal
≤ 185 / 110

Treat with Labetalol 10-20mg IV or Nicardipine 5mg/hr to achieve goal before bolus.

Post-Treatment (24h)
≤ 180 / 105

Monitor: q15m x 2h, then q30m x 6h, then q1h x 16h.

Pediatric Considerations

For children with disabling deficits and confirmed large vessel occlusion (MRI preferred), Alteplase 0.9 mg/kg is the standard of care. Tenecteplase is not yet established for pediatric use.

Complications & Management

Orolingual Angioedema

Mechanism: Plasmin activates kinin pathway → Bradykinin release. High risk with ACE Inhibitors.

  1. Stop infusion immediately.
  2. Methylprednisolone 125mg IV.
  3. Diphenhydramine 50mg IV + Famotidine 20mg IV.
  4. Epinephrine (0.3ml 1:1000 IM) or nebulized racemic epi if airway threatened.
  5. Consider Icatibant if refractory.

Hemorrhage / ICH Rescue

Suspect if headache, nausea, or acute hypertension develops.

  • Stop infusion. Stat Head CT. Check Fibrinogen.
  • Cryoprecipitate: 10 units (raise Fibrinogen >150).
  • Tranexamic Acid: 1000 mg IV over 10 mins.
  • Aminocaproic Acid: 4-5 g IV over 1 hour.

STEMI (ACS)

Indication: Symptom onset < 12h AND Primary PCI cannot be performed within 120 mins.
Goal: Door-to-Needle < 30 mins.

Agent Dosing Protocol Notes
Tenecteplase
Single Weight-Based Bolus (Max 50mg)
< 60 kg: 30 mg 60-70 kg: 35 mg 70-80 kg: 40 mg 80-90 kg: 45 mg ≥ 90 kg: 50 mg
Reduce dose by 50% if age ≥ 75 years.
Alteplase
Accelerated Infusion (Total 100mg)
  • 1. 15 mg IV Bolus.
  • 2. 0.75 mg/kg (max 50 mg) over 30 min.
  • 3. 0.50 mg/kg (max 35 mg) over 60 min.
 More complex administration than TNK.

References

  1. 2026 AHA/ASA Guideline for the Early Management of Patients With Acute Ischemic Stroke.
  2. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction.
  3. Neurocritical Care Society Guidelines for Reversal of Antithrombotics (2016).