A PSA on TXA: Updated recommendations for TXA in Trauma
/Tranexamic acid (TXA) is an anti-fibrinolytic agent that is often used to stop various types of hemorrhage. Guidelines on TXA administration particularly in trauma patients have been mixed due to inconsistent results and concerns about adverse effects from initial studies, but more recent studies demonstrate that TXA is safe and may even reduce mortality in certain trauma patients. Join Dr. Segev as he summarizes the prior major literature on TXA and discusses the recently updated Eastern Association for the Surgery of Trauma (EAST) guidelines regarding the pre-hospital and in-hospital use of TXA in trauma.
Dumas, R.P., Succar, B., Vella, M.A., Appelbaum, R.D., Neal, M.D., Dultz, L.A., Shah, K.H., Patel, N.J., Brito, A., Kornblith, L.Z., Murphy, P.B., Bankhead, B.K., Sleet, M.C., Molavi, I., Asfaw, S., Schreiber, M.A., Kutcher, M.E., Sperry, J.L., Yang, W., Cannon, J.C., & Martin, M.J. (2025). The use of tranexamic acid in the management of injured patients at risk of hemorrhage: a systematic review and meta-analysis and an Eastern Association for the Surgery of Trauma Practice Management Guideline. The journal of trauma and acute care surgery.
Background
Tranexamic acid, or “TXA,” is an anti-fibrinolytic agent that inhibits fibrinolysis by blocking the lysine binding site on plasminogen, preventing activation of plasminogen to plasmin thereby preventing plasmin from breaking down fibrin clots.
TXA is also theorized to have pleiotropic effects extending beyond its pro-coagulation effects, including possible anti-inflammatory and protective endothelial effects.
TXA likely benefits the subset of trauma patients who are prone to hyperfibrinolysis from tissue trauma and a dysregulated immune response.
In the last 2 decades, there have been 3 notable large, randomized-controlled trials (RCTs) examining TXA in the trauma patient at risk of hemorrhage.
Despite TXA’s promise, the primary outcomes from these RCTs appear to be mixed and inconclusive, which has lead to concerns about the benefits of TXA administration given the theoretical increased risk of vaso-occlusive events.
We will explore 3 RCTs before discussing EAST’s new meta-analysis and TXA guidelines as the best data from this meta-analysis is derived from these 3 studies.
CRASH-2 (2013)
STAAMP (2020)
PATCH-Trauma (2023)
1) CRASH-2 (2013) - The first randomized controlled trial studying TXA in trauma
Population: 20,000 adult trauma patients at risk of hemorrhagic shock were enrolled in-hospital across 274 hospitals over 40 countries from 2005 to 2010
Inclusion criteria: injury within 8 hours of enrollment + signs of hemorrhage (defined as HR > 110bpm OR SBP < 90 mmHg) OR clinical concern for risk of hemorrhage
Exclusion criteria: if clinician felt there was NOT clinical equipoise regarding TXA administration, meaning those patients felt to definitely benefit from TXA administration were excluded
Intervention: In-hospital administration of 1g bolus of TXA followed by 1g over 8 hours
Control: Saline administration
Outcomes: Primary outcome was mortality at 28 days with secondary outcomes including blood transfusions and vaso-occlusive events
Results:
Statistically significant improvement in 28 day mortality rate favoring TXA (relative risk 0.91; 14.5% vs 16%)
In subgroup analysis, this mortality benefit appeared concentrated in the <1hr and 1-3 groups compared with the >3 hr group where there did not appear to be any mortality benefit
No statistically significant difference in amount of blood products transfused, which may be confounded by survivorship bias as those that survived received more blood products over time
No statistically significant different in vaso-occlusive events
2) STAAMP (2020)
Population: 927 adult trauma patients with prehospital hemorrhage were enrolled before arrival to 4 different US level 1 trauma centers from 2015 to 2019
Inclusion criteria: injury occurred within 2 hours + signs of hemorrhage (HR > 110 or SBP < 90)
Intervention: Primary randomization to 1g of TXA over 10 minutes pre-hospital, with secondary randomization after hospital arrival to receive up to 2 additional TXA doses
Control: Saline administration
Outcomes: Primary outcome was 30 day all cause mortality with secondary outcomes including blood transfusions and vaso-occlusive events
Results:
No statistically significant in 30 day mortality between TXA and placebo, but there was a trend favoring TXA (RR 0.81; 8.1% in TXA vs. 9.9% in control)
In subgroup analysis, TXA administration within 1hr of injury did have a statistically significant decrease in mortality (RR 0.60; 4.6% in TXA vs 7.6% in control)
No statistically significant difference in amount of blood products transfused
No statistically significant difference in vaso-occlusive events
Limitation: Notably, this trial was heavily limited by a population which was significantly less sick than expected, as 24hr mortality in both groups was less than 4%, on average 0 patients in each group received a blood transfusion within 24 hours, and overall mortality in the placebo group was around half of what was expected
3) PATCH-Trauma (2023)
Population: 1310 adult trauma patients at risk of prehospital hemorrhage were enrolled before hospital arrival in Europe
Inclusion criteria: injury occurred within 3 hours + deemed to be at risk of traumatic coagulopathy based on the validated COAST score
Intervention: Pre-hospital administration of 1g bolus of TXA followed by 1g infusion
Control: Saline administration
Outcomes: Primary outcomes were the incidence of favorable functional outcomes at 6 months defined by a Glasglow Outcome Scale Extended score (GOS-E) of 5 or greater. Secondary outcomes included 28 day and 6-month mortality and vaso-occlusive events
Results:
No statistically significant in functional outcomes at 6 months (53.7% in TXA vs. 53.5% in control)
There was, however, a statistically significant decrease in 28-day (17.3% vs 21.8%) and 6-month mortality (19% vs 22.9%) favoring TXA
The increased survivorship in the TXA group appeared to be those patients with a GOS-E score of 2, indicating “vegetative state”
No statistically significant difference in vaso-occlusive events
Limitations: 13% lost to follow-up
Our journal article focus for today —> EAST Systematic Review and Meta-Analysis regarding TXA administration in adult trauma patients at risk for hemorrhage (2025)
EAST performed a systematic review and meta-analysis of existing literature examining TXA in trauma patients at risk of hemorrhage (defined as patients with signs of hemorrhage [SBP <= 90mmHg or HR >= 110bpm] or clinical suspicion for active hemorrhage) to answer four primary questions (noted below)
Question #1: Should you give TXA in-hospital to adults at risk of hemorrhage?
24-hour and 1-month mortality had statistically significant logarithmic risk-ratios favoring TXA (-0.38 and -0.24, respectively).
10 workgroup members strongly recommended TXA and the remaining 9 conditionally recommended it, leading to an overall conditional recommendation for in-hospital use of TXA in patients at risk of hemorrhage.
Question #2: Should you give TXA pre-hospital to adults at risk of hemorrhage?
24-hour and 1-month mortality had statistically significant logarithmic risk-ratios favoring TXA (-0.29 and -0.18, respectively).
Again, 10 workgroup members strongly recommended TXA and the remaining 9 conditionally recommended it, leading to an overall conditional recommendation for prehospital use of TXA in patients at risk of hemorrhage
Question #3: What dose of TXA should you give?
No recommendation was made regarding low dose (1-2g) versus high dose (3-4g) TXA administration due to a paucity of evidence
Question #4: Does severe hypotension change the recommendation?
No, the work-group made similar recommendations and conditionally recommended TXA
Notably, there were no statistically significant differences in vaso-occlusive events between groups
Meta analysis as a whole measured:
Primary outcomes of 24 hour mortality and 28/30-day mortality between TXA versus placebo groups in both pre-hospital and in-hospital settings
Safety outcomes such as vaso-occlusive events
Discussion
Although some of the individual RCTs did not reach impressive statistical significance, this meta-analysis DID demonstrated a statistically significant decrease in both 24-hour and 28/30-day mortality in trauma patients who received TXA, indicating there is likely a mortality benefit from TXA administration.
CRASH-2 and STAAMP indicate this mortality benefit is concentrated in the hyperacute window within 3 hours of injury, and more recent post-hoc analysis of PATCH suggests it may be further concentrated within 90 minutes of injury.
The functional outcomes of the survivors is questionable based on the results of PATCH which indicated that the patients who had a mortality benefit from TXA administration were those left in a vegetative state.
Importantly, this meta-analysis demonstrates that TXA is safe and does not cause any statistically significant increase in vaso-occlusive events.
Take-Aways
This meta-analysis provides support if you choose to administer TXA to trauma patients who you deem at risk of hemorrhage, although the recommendations remain conditional due to overall low evidence.
TXA likely provides some mortality benefit in trauma patients at risk of hemorrhage, but that effect is likely concentrated in the hyperacute period (<3 hours of injury, potentially <90 minutes of injury) and is likely only to benefit patients who experience a hyperfibrinolytic state, which is a small subset of trauma patients.
Additionally, the functional outcomes in those patients who benefit from TXA administration remain unclear based on the results of the PATCH RCT.
TXA has been proven to have an excellent safety profile without any statistically significant risk of vaso-occlusive events
Given the possible mortality benefit, low risk of harm, generally low cost of administration, and likely benefit only if given within the hyperacute window, I plan to more frequently call for TXA early on the resuscitation of a trauma patient who I am concerned may have clinically significant hemorrhage.
AUTHORSHIP
Written by: Eric Segev, MD, PGY-3 University of Cincinnati Department of Emergency Medicine
Editing, Posting, and Audio Editing by Anita Goel, MD Adjunct Associate Professor, University of Cincinnati Department of Emergency Medicine.
Cite as: Segev, E., Goel, A. A PSA on TXA: Updated recommendations for TXA in Trauma. TamingtheSRU.com. www.tamingthesru.com/blog/journal-club-updated-east-trauma-guidelines-for-txa-use. 11/26/2025.
