Tranexamic Acid Dosing for Intracerebral Hemorrhage
For adults with spontaneous intracerebral hemorrhage presenting within 8 hours, administer tranexamic acid 1 g intravenously over 10 minutes as a loading dose, followed by 1 g infused over 8 hours. 1, 2, 3
Standard Dosing Protocol
The evidence-based regimen consists of:
This dosing protocol is derived from the landmark CRASH-2 trauma trial and has been adopted for intracerebral hemorrhage based on the TICH-2 trial, which specifically evaluated 2,325 ICH patients using this exact regimen. 5, 6
Critical Timing Considerations
Administer tranexamic acid as early as possible and ideally within 3 hours of symptom onset. 1, 2, 3
The timing of administration is crucial:
- Effectiveness decreases by 10% for every 15-minute delay 1, 2, 3
- Treatment within 1 hour significantly reduces mortality due to bleeding 2, 7
- Treatment between 1-3 hours still provides benefit 7
- Administration after 3 hours may paradoxically increase risk of death due to bleeding 2, 3, 7
While the TICH-2 trial allowed enrollment up to 8 hours, subgroup analysis from trauma data and meta-analyses suggest maximal benefit occurs when treatment is initiated within 4.5 hours. 8 The trial protocol permitted 8-hour enrollment, but the majority of participants were actually treated after 4.5 hours, which may explain why functional outcomes at 90 days did not differ despite reductions in early death and hematoma expansion. 5, 6
Evidence from Intracerebral Hemorrhage Trials
The TICH-2 trial demonstrated that tranexamic acid:
- Reduced early deaths by day 7 (9% vs 11% in placebo; adjusted OR 0.73) 6
- Reduced serious adverse events at days 2,7, and 90 6
- Did not significantly improve functional status at 90 days (the primary outcome) 5, 6
- Did not increase thromboembolic events or seizures 5, 6
Meta-analysis suggests TXA reduces hematoma expansion (OR 0.825), particularly in high-risk populations with CT markers of expansion and when administered within 4.5 hours. 8
Safety Profile and Contraindications
Do not exceed a total dose of 100 mg/kg to minimize seizure risk. 1, 2
Key safety considerations:
- Higher doses are associated with increased seizure risk, particularly in cardiac surgery patients 1, 2, 3
- No increase in thromboembolic events (myocardial infarction, stroke, pulmonary embolism) was observed in ICH trials 5, 6
- Absolute contraindication: subarachnoid hemorrhage due to risk of cerebral edema and infarction 2
- Reduce dosing in renal impairment as tranexamic acid is predominantly renally excreted 2
Route of Administration
Intravenous administration is the only evidence-based and FDA-approved route for acute hemorrhage. 2, 3
Current guidelines do not support intramuscular or other alternative routes for ICH. 1, 3
Common Pitfalls to Avoid
- Delaying treatment beyond 3 hours: This significantly reduces effectiveness and may increase mortality 1, 2, 3, 7
- Using in ischemic stroke candidates for thrombolysis: TXA could theoretically counteract thrombolytic benefits 1, 3
- Administering to patients with subarachnoid hemorrhage: This is contraindicated 2
- Exceeding recommended total dose: Doses above 100 mg/kg increase seizure risk 1, 2
Clinical Context
While tranexamic acid shows biological efficacy in reducing hematoma expansion and early deaths in ICH, the lack of improvement in 90-day functional outcomes in TICH-2 likely reflects late treatment timing (median >4 hours) and inclusion of patients with very large hemorrhages who had poor prognosis regardless of intervention. 5, 6 The evidence suggests greatest benefit when administered within 3 hours to patients at high risk of hematoma expansion. 7, 8