In adults with acute spontaneous intracerebral hemorrhage, what are the indications, recommended dosing, benefits, and risks of tranexamic acid (TXA) when administered within three hours of symptom onset?

Tranexamic Acid in Acute Spontaneous Intracerebral Hemorrhage

Tranexamic acid (TXA) reduces hematoma expansion in acute spontaneous intracerebral hemorrhage but does not improve functional outcomes or mortality at 90 days, and should be administered as 1 g IV over 10 minutes followed by 1 g IV over 8 hours within 3 hours of symptom onset in selected patients. 1, 2

Critical Timing Requirements

The 3-hour window is absolute and non-negotiable:

• TXA effectiveness decreases by 10% for every 15-minute delay in administration 1, 3
• Treatment within 1 hour provides maximum benefit for reducing early mortality 1
• Administration after 3 hours may paradoxically increase the risk of death due to bleeding 1, 3
• Most benefit occurs when treatment is initiated within 4.5 hours, particularly in high-risk populations 4

Standard Dosing Protocol

The evidence-based regimen from the TICH-2 trial:

• Loading dose: 1 g intravenous tranexamic acid over 10 minutes 1, 2
• Maintenance infusion: 1 g intravenous tranexamic acid over 8 hours 1, 2
• This achieves therapeutic plasma levels necessary to inhibit systemic fibrinolysis 3

Patient Selection and Indications

TXA should be considered in:

• Adults (≥18 years) with acute spontaneous intracerebral hemorrhage presenting within 8 hours of onset 2
• Highest benefit in patients with CT markers of hematoma expansion (spot sign, black hole sign, blend sign) treated within 4.5 hours 4, 5
• Patients without prestroke dependence (modified Rankin Scale ≤4) 2
• Glasgow Coma Scale score ≥5 2

Absolute Contraindications

Do not administer TXA in:

• Subarachnoid hemorrhage (risk of cerebral edema and infarction) 1
• ICH secondary to anticoagulation, thrombolysis, or trauma 2
• ICH from known underlying structural abnormality 2
• Renal impairment without dose adjustment (TXA is 90% renally excreted) 1
• Patients presenting >3 hours after symptom onset (may increase bleeding-related mortality) 1, 3

Evidence of Benefits

Proven effects:

• Reduces hematoma expansion: 40.4% with TXA vs 41.5% with placebo in TICH-2, with meta-analysis showing OR 0.825 (95% CI 0.69-0.98) 2, 4
• Reduces early mortality by day 7: adjusted OR 0.73 (95% CI 0.53-0.99) 2
• Decreases serious adverse events at days 2,7, and 90 2
• Greatest benefit in high-risk populations with CT markers of expansion: OR 0.646 (95% CI 0.50-0.83) 4

Limitations:

• No improvement in 90-day functional outcomes (modified Rankin Scale shift) or 90-day mortality 2, 4, 6
• The TICH-2 trial enrolled most patients >4.5 hours after onset, potentially diluting treatment effect 2

Safety Profile

TXA is safe in ICH:

• No increase in thromboembolic events: RR 1.20 (95% CI 0.85-1.69) 2, 6
• No increase in seizures 2
• Fewer serious adverse events compared to placebo 2
• Do not exceed 100 mg/kg total dose to minimize seizure risk, particularly in patients >50 years 1

Implementation Algorithm

Step 1: Rapid assessment on arrival

• Confirm spontaneous ICH on non-contrast CT
• Document exact time of symptom onset (or last known normal)
• Calculate time window: must be ≤3 hours from onset 1, 3

Step 2: Eligibility screening

• Age ≥18 years, GCS ≥5, prestroke mRS ≤4 2
• Exclude anticoagulation-related ICH, trauma, structural lesions 2
• Check for subarachnoid hemorrhage (absolute contraindication) 1
• Assess renal function (adjust dose if impaired) 1

Step 3: Immediate administration

• Do not delay for coagulation studies or additional imaging 7
• Administer 1 g IV over 10 minutes 1, 2
• Immediately follow with 1 g IV infusion over 8 hours 1, 2

Step 4: Monitoring

• Obtain 24-hour follow-up CT to assess hematoma expansion 2, 5
• Monitor for thromboembolic complications (though risk is not increased) 2, 6

Critical Pitfalls to Avoid

• Never administer TXA >3 hours after symptom onset – this converts potential benefit to harm 1, 3
• Do not use in subarachnoid hemorrhage – increases risk of cerebral edema and infarction 1
• Do not delay treatment while awaiting laboratory results beyond initial CT scan 7
• Do not confuse with ischemic stroke protocols – TXA is contraindicated in ischemic stroke patients receiving thrombolytics 7
• Do not use higher doses than the standard protocol – increases seizure risk without proven additional benefit 1, 3
• Do not withhold based on lack of mortality benefit – early death reduction and hematoma expansion prevention are clinically meaningful 2, 4

Nuances in the Evidence

The TICH-2 trial (2,325 patients) showed no functional benefit despite reducing hematoma expansion and early deaths, likely because most patients were treated >4.5 hours after onset 2. Meta-analyses consistently demonstrate that patients treated within 4.5 hours and those with high-risk CT markers derive the greatest benefit 4. The TRAIGE trial found no significant reduction in hematoma growth when treating patients up to 8 hours, reinforcing the critical importance of early administration 5. Current evidence suggests TXA is most appropriately used as a time-sensitive intervention in the hyperacute phase (<3 hours) in patients with imaging markers of expansion risk 1, 4.