What is the role of intravenous (IV) tranexamic acid (TXA) in the management of traumatic brain injury (TBI), including mild, moderate, and severe cases?

IV Tranexamic Acid in Traumatic Brain Injury

Administer IV tranexamic acid (1 g over 10 minutes followed by 1 g over 8 hours) to TBI patients with mild-to-moderate injury within 3 hours of trauma, but the benefit is uncertain in severe TBI. 1

Patient Selection by Injury Severity

Mild-to-Moderate TBI (GCS 9-12 or higher)

• TXA significantly reduces head injury-related death (RR 0.78,95% CI 0.64-0.95) when administered within 3 hours. 1, 2
• The CRASH-3 trial demonstrated mortality reduction from 14.0% to 12.5% in patients with GCS >3 and reactive pupils. 2, 3
• Treatment is highly cost-effective at £4,288 per quality-adjusted life-year gained in this population. 3
• Administer empirically without waiting for CT confirmation or viscoelastic testing results. 1, 4

Severe TBI (GCS 3-8)

• No mortality benefit demonstrated in severe TBI (RR 0.99,95% CI 0.91-1.07). 1, 2
• Patients with GCS of 3 or bilateral unreactive pupils showed no benefit from TXA. 2, 3
• However, in polytrauma with mixed injury patterns, early administration remains reasonable as extracranial bleeding may coexist. 4
• Recent machine learning analysis suggests benefits may persist beyond 3 hours in patients with GCS <9, though this requires further validation. 5

Critical Timing Requirements

The effectiveness of TXA decreases by 10% for every 15-minute delay in administration. 6, 7

Optimal Treatment Windows

• Greatest benefit occurs when administered within 1-2 hours of injury (65% lower 30-day mortality with shock index <0.9). 1, 5
• Treatment within 3 hours reduces head injury-related death from 19.8% to 18.5% overall. 2
• Administration after 3 hours may increase risk of death due to bleeding and should be avoided. 6, 7
• Pre-hospital administration should be initiated whenever feasible to ensure early treatment. 1, 7

Dosing Protocol

Standard regimen: 1 g IV loading dose over 10 minutes, followed by 1 g IV infusion over 8 hours. 1, 4

• Initiate as soon as possible after injury, ideally en route to hospital. 1
• Do not delay for viscoelastic assessment (TEG/ROTEM) results, as these tests have poor sensitivity for detecting hyperfibrinolysis. 1, 4
• Alternative 2 g bolus regimen showed no additional benefit over standard dosing. 1

Safety Profile

Thromboembolic Risk

• No significant increase in vascular occlusive events (stroke, MI, venous thromboembolism) compared to placebo. 4, 2
• Risk ratio for vascular occlusive events: 0.98 (95% CI 0.74-1.28). 2

Seizure Risk

• Seizure risk similar to placebo (RR 1.09,95% CI 0.90-1.33) at standard TBI dosing. 4, 2
• Higher doses used in cardiac surgery are associated with increased seizure risk, but this does not apply to standard TBI dosing. 6, 4

Common Pitfalls to Avoid

Timing Errors

• Delaying administration beyond 3 hours eliminates benefit and may cause harm. 6, 7, 5
• Waiting for laboratory confirmation of hyperfibrinolysis wastes critical treatment time. 1, 4
• Early treatment (≤1 hour) is associated with significantly lower mortality, multiorgan failure, and transfusion requirements. 1

Patient Selection Errors

• Do not withhold TXA in polytrauma patients with severe TBI, as they often have mixed injury patterns requiring assessment. 4
• Patients with both pupils reactive benefit more than those with unreactive pupils. 3
• Exclude patients with isolated severe TBI (GCS 3, bilateral unreactive pupils) presenting late, as they derive no benefit. 2, 3

Administration Errors

• Do not use alternative dosing regimens without evidence (standard 1g + 1g protocol is validated). 1
• Intramuscular administration is not recommended; IV route is evidence-based. 6, 7

Contraindications

• Major extracranial bleeding requiring different management priorities. 2
• Presentation beyond 3 hours post-injury (except possibly in severe TBI with GCS <9 per emerging data). 5
• Ischemic stroke patients being considered for thrombolytic therapy. 6