Is tranexamic acid indicated for acute traumatic intracranial hemorrhage, and should it be used for spontaneous intracerebral hemorrhage?

Tranexamic Acid in Brain Bleeds: Evidence-Based Recommendations

Tranexamic acid should be used in traumatic brain injury with mild-to-moderate injury (GCS 9-15) when administered within 3 hours of injury, ideally within 1 hour, but it is NOT recommended for routine use in spontaneous (non-traumatic) intracerebral hemorrhage as it does not improve functional outcomes or mortality despite reducing hematoma expansion. 1, 2

Traumatic Brain Injury (TBI)

When to Use TXA

For mild-to-moderate TBI, tranexamic acid reduces head injury-related death by 22% (RR 0.78,95% CI 0.64-0.95) when given within 3 hours of injury. 2

• Patients treated within 1 hour show the greatest benefit with 65% lower 30-day mortality (HR 0.35,95% CI 0.19-0.65) 2
• Treatment benefit decreases by approximately 10% for every 15-minute delay 2
• Patients with both pupils reactive at baseline demonstrate the most cost-effective mortality reduction 2

Critical Exclusions for TBI

Do NOT use tranexamic acid in severe TBI patients with GCS 3 or bilateral unreactive pupils—these patients do not benefit and may be harmed. 2, 3

• Treatment after 3 hours may actually increase mortality risk (RR 1.44,95% CI 1.12-1.84) and should be avoided 2
• Severe TBI patients (GCS 3-8 with unreactive pupils) showed no reduction in head injury death (RR 0.99,95% CI 0.91 to 1.07) 3

Dosing Protocol for TBI

• Loading dose: 1 g IV over 10 minutes 2
• Maintenance: 1 g IV infusion over 8 hours 2
• Consider pre-hospital administration to ensure treatment within the critical 1-hour window 2

Spontaneous (Non-Traumatic) Intracerebral Hemorrhage

The American Heart Association/American Stroke Association and European Stroke Organisation do NOT recommend routine use of tranexamic acid for spontaneous ICH, including hypertensive hemorrhage, as it reduces hematoma expansion but does not improve functional outcomes or mortality. 1

Why Not to Use in Spontaneous ICH

• No significant impact on mortality (RR 1.02,95% CI 0.88-1.19) 1, 4
• No improvement in poor functional outcomes (RR 0.98,95% CI 0.93-1.04) 1, 4
• Many factors beyond hematoma expansion determine clinical outcome, including baseline hemorrhage volume, level of consciousness, intraventricular hemorrhage, age, and comorbidities 1
• Do not use TXA based solely on radiographic endpoints—hematoma expansion reduction does not equal improved patient outcomes in non-traumatic hemorrhage 1

Subarachnoid Hemorrhage (SAH)

Tranexamic acid reduces rebleeding risk in aneurysmal SAH (RR 0.6,95% CI 0.44-0.8) but increases cerebral ischemia/stroke risk (RR 1.29,95% CI 1.01-1.67), with no net improvement in outcomes. 1, 4

• The increased stroke risk offsets the rebleeding benefit 4
• Not recommended for routine use in SAH 1

Safety Profile Across All Brain Bleeds

Tranexamic acid does not significantly increase overall thromboembolic events when used appropriately (within 3 hours, for ≤1 day). 1, 5

Important Safety Caveats

• Prolonged administration (>1 day) is associated with increased thromboembolic events (RR 1.22,95% CI 1.03-1.44) 5
• Administration beyond 8 hours of injury increases thromboembolic risk (RR 1.16,95% CI 1.02-1.33) 5
• The increased cerebral ischemia risk in SAH patients is a notable exception to the otherwise favorable safety profile 1

Common Pitfalls to Avoid

• Do not delay administration for diagnostic workup—give TXA empirically in eligible TBI patients before advanced imaging if clinical suspicion exists 2
• Do not treat beyond 3 hours in TBI—this may increase mortality 2
• Do not use in severe TBI with unreactive pupils—resources are better allocated elsewhere 2
• Do not expect functional improvement in spontaneous ICH—radiographic improvement does not translate to clinical benefit 1