Is Tranexamic acid (TXA) indicated for intracranial hemorrhage?

From the Guidelines

Tranexamic acid (TXA) is indicated for intracranial hemorrhage, particularly in traumatic brain injury (TBI) when administered within 3 hours of injury, as it has been shown to reduce head injury-related deaths in patients with mild to moderate TBI. The recommended dosage is 1 gram of TXA given intravenously over 10 minutes, followed by an infusion of 1 gram over 8 hours 1. This treatment approach is supported by the CRASH-3 trial, which demonstrated that early administration of TXA reduced head injury-related deaths in patients with mild to moderate TBI without increasing the risk of vascular occlusive events 1.

Key Considerations

• TXA works by inhibiting plasminogen activation, which prevents the breakdown of blood clots and reduces ongoing bleeding.
• The effectiveness of TXA appears to be limited in severe TBI or when given beyond the 3-hour window 1.
• When administering TXA, it is essential to monitor for potential side effects, including nausea, vomiting, hypotension with rapid infusion, and rarely, seizures or thrombotic complications.
• TXA should be used cautiously in patients with a history of thromboembolic disease, and dose adjustment is necessary in patients with renal impairment.

Clinical Decision-Making

The decision to use TXA in patients with intracranial hemorrhage should be based on the individual patient's risk factors, the severity of the injury, and the potential benefits and risks of treatment. As noted in the European guideline on management of major bleeding and coagulopathy following trauma, TXA has become one of the mainstays of therapy for the injured patient at risk of bleeding 1. However, the use of TXA may not result in a reduction in mortality or disability in all patients, and the clinical relevance of these findings is unclear 1.

Administration and Monitoring

The administration of TXA should be guided by the patient's clinical condition, and monitoring for potential side effects is crucial. The European Society of Intensive Care Medicine recommends the use of TXA in patients with mild to moderate TBI, given the demonstrated safety profile of TXA in this population, the possibility of concomitant non-head injuries for which TXA is indicated, and the low cost and acceptability and feasibility of the intervention 1.

From the FDA Drug Label

4 CONTRAINDICATIONS

Tranexamic acid is contraindicated: In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by tranexamic acid in such patients. In patients with active intravascular clotting [see WARNINGS AND PRECAUTIONS (5.1)].

Tranexamic acid (TXA) is not indicated for intracranial hemorrhage, and in fact, it is contraindicated in patients with subarachnoid hemorrhage due to the risk of cerebral edema and cerebral infarction 2.

From the Research

Indications for Tranexamic Acid in Intracranial Hemorrhage

• Tranexamic acid (TXA) is an antifibrinolytic with anti-inflammatory properties that has been studied for its potential to reduce mortality and morbidity in patients with intracranial hemorrhage (ICH) 3, 4, 5, 6.
• The evidence suggests that TXA may reduce hematoma expansion in spontaneous, nontraumatic intracranial hemorrhage, although it does not seem to improve functional outcomes 3, 4.
• In traumatic brain injury, TXA may reduce head injury-related mortality if treatment occurs within 1 hour of symptom onset, but the findings are inconsistent and more research is needed to determine its effectiveness 3, 5.
• TXA may also prevent rebleeding in aneurysmal subarachnoid hemorrhage, but its impact on outcomes and mortality is unclear 3, 4.

Efficacy and Safety of Tranexamic Acid

• A meta-analysis found that TXA significantly inhibited hematoma growth in ICH and traumatic brain injury patients, and reduced the risk of hydrocephalus and rebleeding in subarachnoid hemorrhage patients 4.
• Another study found that TXA was associated with a 22% decrease in mortality in patients with non-traumatic intracranial bleeding, particularly in those with subarachnoid hemorrhage 6.
• TXA is generally well tolerated, with most adverse reactions considered mild or moderate, although high doses have been associated with seizures and other adverse effects 7.

Clinical Use and Controversies

• The use of TXA in intracranial hemorrhage is still a topic of debate, with some studies suggesting its potential benefits and others raising concerns about its effectiveness and safety 3, 4, 5.
• More research is needed to determine the optimal dosage, route, and interval of administration of TXA, as well as its potential benefits and risks in different patient populations 7, 5.