Is tranexamic acid (TXA) effective in treating intracranial hemorrhage?

Tranexamic Acid Use in Intracranial Hemorrhage

Tranexamic acid (TXA) has not demonstrated consistent improvement in clinical outcomes for intracranial hemorrhage despite showing modest reductions in hemorrhage expansion in some studies. Based on current evidence, TXA cannot be routinely recommended for treatment of intracranial hemorrhage 1, 2.

Evidence by Type of Intracranial Hemorrhage

Non-traumatic Intracerebral Hemorrhage (ICH)

• TXA shows no significant impact on mortality (RR 1.02,95% CI 0.88-1.19) or poor functional outcomes (RR 0.98,95% CI 0.93-1.04) in non-traumatic ICH 1
• While TXA significantly reduces hematoma growth in ICH (mean difference -1.76,95% CI -2.78 to -0.79), this has not translated to improved clinical outcomes 3
• Current guidelines make no recommendation regarding TXA use in non-traumatic ICH due to moderate evidence of no effect on clinically important outcomes 1

Aneurysmal Subarachnoid Hemorrhage (SAH)

• TXA reduces the risk of rebleeding in SAH (RR 0.6,95% CI 0.44-0.8) but increases the risk of cerebral ischemia/stroke (RR 1.29,95% CI 1.01-1.67) 1
• No significant impact on mortality (RR 1.01,95% CI 0.88-1.16) or poor functional outcomes (RR 1.05,95% CI 0.95-1.15) has been demonstrated 1
• The ULTRA trial and other recent studies found small reductions in hemorrhage growth but no statistically significant effect on clinical outcomes 1
• Guidelines make no recommendation regarding TXA use in SAH due to the offsetting risks and benefits 1

Traumatic Brain Injury (TBI)

• The CRASH-3 trial showed TXA may reduce head injury-related death in patients with mild to moderate TBI (RR 0.78,95% CI 0.64-0.95) when given within 3 hours of injury 4
• However, TXA showed no benefit in severe TBI (RR 0.99,95% CI 0.91-1.07) 4
• TXA may prevent new hemorrhage formation in TBI patients with reactive pupils at baseline 5
• Time to treatment appears critical, with greater benefit when administered within 1 hour of injury in mild-moderate TBI 4, 2

Clinical Implementation Considerations

• Early administration (within 3 hours of symptom onset, ideally within 1 hour) is essential if TXA is to be used 1, 4
• Patient selection is crucial - those with very large hemorrhages are unlikely to benefit as reduction of further bleeding would have minimal impact 1
• Location of hemorrhage should be considered, as deep bleeds have higher risk of early expansion compared to lobar hemorrhages 1
• The risk-benefit profile differs by hemorrhage type:
  • In SAH: Reduced rebleeding must be weighed against increased stroke risk 1
  • In ICH: Modest reduction in hematoma growth has not translated to clinical benefit 1
  • In TBI: Potential benefit in mild-moderate injury with early treatment, but not in severe TBI 4

Safety Considerations

• TXA has not shown significant increases in thromboembolic events across studies of intracranial hemorrhage 1, 2
• Rates of deep vein thrombosis, pulmonary embolism, and myocardial infarction are similar between TXA and placebo groups 3, 4
• The increased risk of cerebral ischemia in SAH patients is a notable exception to the otherwise favorable safety profile 1

Future Directions

• Ongoing trials are investigating TXA in specific contexts:
  • Treatment of ICH in patients on direct oral anticoagulants 1
  • Ultra-early administration via mobile stroke units 1
  • Combined approaches with other hemostatic agents 1
• Further research is needed to identify specific patient subgroups most likely to benefit from TXA and to establish optimal dosing and timing strategies 2, 6