What is the role of tranexamic acid (TXA) in managing brain bleed?

From the Guidelines

Tranexamic acid (TXA) should be administered to patients with traumatic brain injury within 3 hours of injury, with a recommended dose of 1 gram given intravenously over 10 minutes, followed by another 1 gram infused over 8 hours. This is based on the most recent and highest quality evidence from the CRASH-3 trial 1, which demonstrated that early treatment with TXA reduced the risk of head injury-related death in patients with mild and moderate head injury. The European guideline on management of major bleeding and coagulopathy following trauma also recommends the use of TXA in traumatic brain injury, with a strong recommendation and high certainty of evidence 1.

The mechanism of action of TXA involves inhibiting the breakdown of blood clots, which can potentially limit hematoma expansion in brain bleeds. However, TXA is not routinely recommended for spontaneous intracerebral hemorrhage (ICH) as large clinical trials have shown no significant improvement in functional outcomes or mortality, despite some reduction in hematoma growth. The TICH-2 trial demonstrated that while TXA reduced early death and hematoma expansion in spontaneous ICH, it did not improve functional status at 90 days.

Some key points to consider when using TXA in traumatic brain injury include:

• Administration of TXA should not await results from viscoelastic assessment 1
• TXA should be given as soon as possible, if feasible en route to the hospital, and within 3 hours after injury 1
• The dose of TXA given should be a loading dose of 1 gram IV over 10 minutes, followed by 1 gram IV over 8 hours 1
• Early empiric use of the loading dose of TXA is recommended prior to point of care testing, as earlier administration of TXA may be more effective at reducing mortality 1

Overall, the use of TXA in traumatic brain injury is supported by high-quality evidence, and its administration within 3 hours of injury is recommended to reduce the risk of head injury-related death.

From the FDA Drug Label

In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by tranexamic acid in such patients.

The role of tranexamic acid (TXA) in managing brain bleed is contraindicated in patients with subarachnoid hemorrhage, as it may cause cerebral edema and cerebral infarction 2.

From the Research

Role of Tranexamic Acid in Managing Brain Bleed

• Tranexamic acid (TXA) is used to reduce bleeding and the need for volume replacement in neurosurgery, but its effectiveness and risks are controversial 3.
• In traumatic brain injury (TBI), early administration of TXA (<3h) can decrease mortality in mild-moderate TBI patients, without increasing thromboembolic complications 4.
• The CRASH-3 trial showed that TXA treatment can prevent deaths from post-traumatic intracranial bleeding, especially in patients with reactive pupils and mild to moderate Glasgow Coma Scale (GCS) 5.
• A meta-analysis of 14 randomized controlled trials found that TXA did not improve mortality or reduce poor functional outcomes in patients with cerebral hemorrhage, but it did reduce hematoma expansion and rebleeding 6.
• A study on the effect of intravenous TXA on traumatic intracerebral hemorrhage found that TXA reduced hematoma expansion and can be used to reduce morbidity and complications 7.

Benefits and Risks of Tranexamic Acid

• Benefits:
  • Reduces blood loss and the need for blood transfusion in trauma and spinal surgery 3.
  • Decreases mortality in mild-moderate TBI patients 4.
  • Reduces hematoma expansion and rebleeding in cerebral hemorrhage 6, 7.
• Risks:
  • Moderate-to-high doses of TXA are potentially associated with neurological complications (seizures, transient ischemic attack, delirium) in adults and children 3.
  • Increases the risk of combined ischemic events in cerebral hemorrhage 6.