Early posttraumatic brain injury tranexamic acid prevents blood-brain barrier hyperpermeability and improves surrogates of neuroclinical recovery

Abstract

TXA after TBI, improves rodent BBB integrity and neurological recovery but only if administered early after injury. Late TXA administration increases rolling leukocyte mobilization to the penumbra.

Dose-Dependent Tranexamic Acid Blunting of Penumbral Leukocyte Mobilization and Blood–Brain Barrier Permeability Following Traumatic Brain Injury: An In Vivo Murine Study

“…Relatedly, TXA appears to demonstrate impact beyond bleeding reduction. A small but similar series of reports point to TXA-related reductions in post-tissue injury microvascular hyperpermeability but also occurring in sepsis and shock 12,19,20 . In evaluating any potential neuroprotective modulatory effects of TXA in brain injury, a clear understanding of the underpinning cellular processes occurring following TBI must rst be discussed to understand any impact on TBI outcome and recovery.…”

“…TXA dosing was derived from standard bodyweight dosing for a 70 kg human receiving a 1g (14.3 mg/kg) loading bolus, with augmented double and triple dosing aligned with other published reports 15 . The 1 hour post-TBI TXA administration was selected based on previous work demonstrating reduced BBB in ammation and augmented neuroclinical recovery 12,16 . Forty mice were assigned to one of ve groups (n = 8 for each): (1) sham craniotomy and NS (S + P); (2) CCI and placebo (I + P); (3) CCI and 15 mg/kg TXA (I + TXA15); (4) CCI and 30 mg/kg TXA (I + TXA30); (5) CCI and 60 mg/kg TXA (I + TXA60).…”

“…Most renowned, the CRASH-2 and CRASH-3 trials demonstrated improved survival and outcomes following multiple trauma or TBI in patients receiving early -but not late -TXA 9,10 . Recent intriguing reports suggest that plasmin formation after injury potentiates a pervasive microvascular in ammation that activates both the host innate response and complement suggesting that bene cial post-injury TXA effects may stem from blocking plasmin formation [11][12][13][14] . In these and other reports, post-TBI TXA administration demonstrated improved neurological outcomes associated with greater preservation of BBB integrity, particularly when given early.…”

“…Across multiple studies, only early post-injury TXA improves outcomes, while late TXA may engender harm. Relatedly, while optimal TXA dosing is less clear, improved outcomes may be secured across different dosing regimens 12,15,16 .…”

For patients with TBI-related ICH, a shorter mannitol and tranexamic acid administration interval may contribute to VTE risk

“…As an anti-brinolytic agent, Tranexamic acid (TXA) has long attracted the world's attention for it signi cantly promotes traumatic brain injury (TBI) patients' prognosis [1,2,3]. However, the drug-related potential VTE risk has also been noticed [4,5].…”