In a pediatric patient with acute traumatic brain injury presenting within three hours, what is the recommended tranexamic acid (TXA) dosing and contraindications?

Tranexamic Acid Dosing for Pediatric Traumatic Brain Injury

For pediatric patients with acute traumatic brain injury presenting within 3 hours, administer tranexamic acid at 15 mg/kg IV loading dose over 10 minutes, followed by 2 mg/kg/hour infusion for 8 hours, with treatment initiated as rapidly as possible and absolutely within 3 hours of injury. 1, 2

Pediatric-Specific Dosing Protocol

The weight-based dosing regimen differs from adult protocols and is critical for pediatric TBI:

• Loading dose: 15 mg/kg IV over 10 minutes 1, 2
• Maintenance infusion: 2 mg/kg/hour for 8 hours 1, 2
• Maximum total dose: 100 mg/kg to minimize seizure risk 1

This dosing is supported by current U.S. practice patterns, where 68% of pediatric trauma centers using TXA employ the 15 mg/kg loading dose, and 87% follow with maintenance infusion, most commonly at 2 mg/kg/hour 2.

Critical Timing Requirements

Treatment must begin within 3 hours of injury—this is an absolute deadline, not a suggestion:

• Efficacy decreases by 10% for every 15-minute delay in administration 3, 1
• Early treatment (within 1 hour) provides maximum mortality reduction 3, 1
• Administration after 3 hours may paradoxically increase bleeding-related death risk 3, 1
• In pediatric TBI specifically, treatment within 45 minutes shows lower complication rates including reduced deep venous thrombosis (0.8% vs 3.4%) and cerebral vasospasm (0% vs 2%) 4

The CRASH-3 trial demonstrated that TXA reduces head injury-related death in mild-to-moderate TBI (risk ratio 0.78) when given within 3 hours, though benefit was not seen in severe TBI 3, 5. Recent machine learning analysis of CRASH-2 and CRASH-3 data suggests optimal benefit occurs within 2 hours, with benefits potentially extending beyond 3 hours only in patients with Glasgow Coma Scale <9 6.

Absolute Contraindications in Pediatric TBI

Do NOT administer TXA in the following scenarios:

• Active intravascular clotting or disseminated intravascular coagulation 7
• Severe hypersensitivity to tranexamic acid 7
• Renal impairment without dose adjustment (TXA is 90% renally excreted and accumulates dangerously) 3, 7
• Traumatic subarachnoid hemorrhage as the primary pathology (routine antifibrinolytic therapy does not improve functional outcomes) 8

Relative Contraindications Requiring Extreme Caution

• Massive hematuria (risk of ureteric obstruction) 7
• Patients on oral contraceptive medications (increased thrombosis risk) 7
• Post-stroke patients (thrombotic concerns) 7

Safety Profile in Pediatric Trauma

The safety evidence is reassuring for appropriate dosing:

• No increased thromboembolic risk when used at standard doses in trauma populations 3, 7
• Seizure risk increases with doses >100 mg/kg, particularly in cardiac surgery patients 1
• In the CRASH-3 trial of 12,737 TBI patients, vascular occlusive events (risk ratio 0.98) and seizures (risk ratio 1.09) were similar between TXA and placebo groups 5

Clinical Implementation Algorithm

Step 1: Rapid Assessment (within minutes of arrival)

• Confirm TBI diagnosis and time from injury <3 hours 3, 1
• Assess Glasgow Coma Scale score (mild-moderate TBI shows greatest benefit) 3, 5
• Obtain patient weight for dosing calculation 2
• Check for absolute contraindications (active DIC, severe renal impairment) 7

Step 2: Immediate Administration

• Calculate 15 mg/kg loading dose 1, 2
• Administer IV over 10 minutes 3, 1
• Do not delay for viscoelastic testing or coagulation studies 3

Step 3: Maintenance Infusion

• Begin 2 mg/kg/hour infusion immediately after loading dose 1, 2
• Continue for 8 hours 3, 1
• Ensure total dose does not exceed 100 mg/kg 1

Step 4: Renal Function Monitoring

• Assess creatinine clearance urgently 3, 7
• Reduce dose proportionally for any degree of renal impairment 7

Key Clinical Pitfalls to Avoid

• Never delay administration waiting for laboratory results or imaging beyond initial CT 3
• Do not use adult fixed-dose protocols (1g + 1g) in pediatric patients—weight-based dosing is essential 1, 2
• Do not continue treatment beyond 8 hours or exceed 100 mg/kg total dose due to seizure risk 1
• Do not administer if >3 hours from injury unless GCS <9, where some benefit may persist 6
• Recognize that severe TBI (GCS 3-8) shows less benefit than mild-moderate TBI 3, 5

Special Considerations for Pediatric TBI

While only 35% of U.S. trauma centers caring for pediatric patients currently use TXA 2, the evidence from CRASH-3 and subsequent analyses supports its use in pediatric TBI with hemodynamic instability or significant ongoing hemorrhage risk 2, 5. The treatment represents a low-cost, low-risk intervention with potential high yield when administered within the critical time window 2.