Is tranexamic acid (TXA) indicated in patients with non-traumatic head injury, such as spontaneous intracranial hemorrhage?

Tranexamic Acid is NOT Indicated in Non-Traumatic Head Injury

Tranexamic acid should not be routinely used in patients with non-traumatic intracranial hemorrhage, as it does not improve functional outcomes or reduce mortality despite reducing hematoma expansion. 1

Critical FDA Contraindication

• Tranexamic acid is absolutely contraindicated in patients with subarachnoid hemorrhage due to risk of cerebral edema and cerebral infarction 2
• This FDA contraindication applies specifically to the non-traumatic setting 2

Evidence for Non-Traumatic Intracerebral Hemorrhage (ICH)

Lack of Clinical Benefit Despite Radiographic Improvement

• The American Heart Association/American Stroke Association and European Stroke Organisation do not recommend routine use of TXA for spontaneous ICH 1
• While TXA reduces hematoma expansion (mean difference -1.76 mL, 95% CI -2.78 to -0.79), this does not translate to improved outcomes 3
• 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

Why the Disconnect Between Imaging and Outcomes?

• Many factors beyond hematoma expansion determine clinical outcome after ICH, including baseline hemorrhage volume, level of consciousness, intraventricular hemorrhage presence, age, and comorbidities 4
• Patients with very large hemorrhages are unlikely to benefit, as reduction of further bleeding has minimal impact on overall outcome 1

Evidence for Subarachnoid Hemorrhage (SAH)

Harm Outweighs Benefit

• TXA reduces rebleeding risk in SAH (RR 0.6,95% CI 0.44-0.8) 1
• However, TXA increases the risk of cerebral ischemia/stroke (RR 1.29,95% CI 1.01-1.67) 1
• This increased ischemic risk negates any benefit from reduced rebleeding 1
• TXA may prevent rebleeding but has not led to improved outcomes or reduced mortality in SAH 5

Contrast with Traumatic Brain Injury

• In traumatic brain injury (TBI), TXA shows potential benefit in mild-to-moderate injury when given within 3 hours (RR 0.78,95% CI 0.64-0.95) 6
• This benefit does NOT extend to non-traumatic hemorrhage 1
• The pathophysiology differs between traumatic and non-traumatic bleeding, explaining the divergent results 5

Safety Profile

• TXA has not shown significant increases in thromboembolic events across studies of intracranial hemorrhage 1
• The exception is the increased cerebral ischemia risk specifically in SAH patients 1

Clinical Decision Algorithm

For non-traumatic intracranial hemorrhage:

1. If subarachnoid hemorrhage → Do NOT give TXA (FDA contraindication) 2
2. If spontaneous ICH → Do NOT give TXA routinely (no clinical benefit despite radiographic improvement) 1
3. Consider enrollment in ongoing clinical trials investigating TXA in specific contexts (e.g., ICH in patients on direct oral anticoagulants) 1

Common Pitfalls to Avoid

• Do not extrapolate TBI data to non-traumatic hemorrhage - the evidence showing benefit in mild-to-moderate TBI does not apply to spontaneous ICH 1, 6
• Do not use TXA based solely on radiographic endpoints - hematoma expansion reduction does not equal improved patient outcomes in non-traumatic hemorrhage 4, 1
• Do not ignore the FDA contraindication in SAH - the risk of cerebral edema and infarction is real 2