Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Intracranial hemorrhage progression is a major driver of poor outcomes, and tranexamic acid (TXA), an antifibrinolytic agent, has been proposed to mitigate this by inhibiting clot breakdown. While effective in traumatic extracranial bleeding, its efficacy in TBI remains a subject of debate. This systematic review aimed to critically evaluate evidence from randomized controlled trials (RCTs) on the efficacy and safety of TXA in improving outcomes for patients with traumatic brain injury. A systematic literature search was conducted for RCTs published within the last five years. Adult patients with TBI receiving TXA compared to placebo or standard care were included. Outcomes of interest were mortality, functional neurological status, hemorrhage progression, and adverse events. Seven RCTs were included, with the CRASH-3 trial (n=9,127) being the largest. CRASH-3 found that TXA administered within 3 hours reduced head injury-related mortality in patients with mild to moderate TBI (GCS 9-15) but not in those with severe TBI. Conversely, the prehospital trial found no improvement in 6-month functional outcomes or mortality. Smaller RCTs consistently demonstrated a significant reduction in radiological hemorrhage progression with TXA. The large trials reported no increased risk of thromboembolic events, but several smaller studies did not report safety outcomes. TXA appears to be a safe and effective intervention for reducing mortality in a specific subset of patients with mild to moderate TBI when administered early (

Key words: Tranexamic acid, traumatic brain injury, intracranial hemorrhage, antifibrinolytic agents, mortality, systematic review