Tranexamic acid to prevent bleeding in general surgery
POISE-3 analysis homes in on general surgery patients
Tranexamic acid (TXA) is a synthetic molecule derived from the amino acid lysine. TXA helps induce coagulation through antifibrinolytic effects by reversibly blocking lysine-plasminogen binding sites. This slows plasminogen’s clot-dissolving activity.
A related compound, epsilon-aminocaproic acid (EACA), has similar effects but at ~10% the potency of TXA.
Prophylactic tranexamic acid has been shown to reduce bleeding in multiple surgical and trauma settings, although the effects have been small and less than perfectly consistent across multiple randomized trials.
There is a general belief among surgeons that tranexamic acid (TXA) can reduce perioperative bleeding in some surgeries, but TXA is not a standard preventive treatment in all operations. Among surgeons, the adoption and enthusiasm for TXA depend on the type of surgery, institutional protocols, and concerns about potential thrombotic risks.
A subgroup analysis of a recent trial may convince at least some surgeons to extend the indications for tranexamic acid into general surgery settings.
The POISE-3 Trial
The POISE-3 trial (Devereaux et al NEJM 2022) tested 1 gram of prophylactic TXA vs placebo in a large population (n=9,535) undergoing noncardiac surgery in 22 countries.
TXA has been suspected of causing seizures, so patients with a history of seizures were excluded.
The trial included a mix of surgical indications and sites: general surgery (37%); orthopedic (23%); vascular (15%); urologic (13%); and spinal, gynecologic, thoracic, low-risk, or plastic surgery (12% combined).
POISE-3 was positive overall, with a relative 22% fewer (absolute 2.6% fewer, 9.1% vs 11.7%) TXA patients experiencing serious perioperative bleeding (life-threatening bleeding, major bleeding, or bleeding into a critical organ), compared to placebo-treated patients.
Fewer TXA-treated patients required blood transfusion: the number needed to treat with a 1-gram bolus of TXA to prevent major bleeding was 38.
However, it wasn’t clear if the observed benefits extended to all surgical patients or were concentrated in any particular subgroup.
TXA for All General Surgery Patients?
A new subgroup analysis of POISE-3 (Park et al JAMA Surgery 2025) examined only its general surgery patients, who made up 37% of the total randomized trial sample (n=3,260).
Among this subgroup of general surgery patients, similar benefits of TXA were observed as in the entire POISE-3 population:
8.0% of TXA patients vs. 10.5% placebo patients had major bleeding (hazard ratio 0.74; 95% CI, 0.59-0.93; P = .01), a 2.5% absolute risk reduction (near-identical to the 2.6% absolute reduction seen overall).
No greater numbers of TXA patients experienced a composite of thromboembolic and cardiovascular events.
TXA might have decreased bleeding most in the 332 patients undergoing hepatopancreaticobiliary surgery (HR, 0.55; 95% CI, 0.34-0.91) and the 940 patients receiving colorectal surgery (HR, 0.67; 95% CI, 0.45-0.98). However, the test for interaction across subtypes suggested this may have been due to chance.
Hard to Rule Out All Risks
TXA’s benefits at preventing bleeding and the need for transfusion have been shown consistently enough that they seem highly likely to be real (though not necessarily universal to all surgical patients).
It’s much harder to prove the absence of cardiovascular events, which occur less often but are potentially more dangerous than bleeding events.
To illustrate the challenge, consider a meta-analysis (Tsan et al, Anaesthesia 2023) that combined 191 randomized trials enrolling 40,621 patients testing TXA in surgical settings.
While publication bias was a concern, this meta-analysis found a significant reduction in blood transfusion rates with TXA (9.9% vs. 19.4%).
Although the analysis did not show any association between TXA and cardiovascular events, even a sample this large was considered to have only two-thirds the power needed to confidently rule out excess cardiovascular risk.
POISE-3 enrolled patients at elevated cardiovascular risk, and could not rule out a 0.3% absolute increased risk for cardiovascular events. This is obviously small, but represents a number needed to harm of only 333, which would be quite significant if TXA were to be given routinely for the 300 million surgeries performed annually around the world.
Conclusion
Prophylactic tranexamic acid probably reduces major bleeding in general surgery and many other surgical patients.
It seems safe, and there’s no good evidence that TXA causes cardiovascular events. Due to the infrequency of these events, though, massive trials would be needed to fully disprove any connection.
The American Association of Orthopedic Surgeons strongly recommends TXA be considered for patients undergoing hip or knee arthroplasties, and TXA is widely used.
The American College of Surgeons and the American Surgical Association have not issued formal guidelines recommending the use of tranexamic acid.
Thank you for this review. This is one of the best Medical Substacks around.
Thanks again. Potentially useful recommendation. The safety is likely reassuring. Last weekend had 88yo guy bad gi bleed - got scoped had duodenal ulcer a visible type of vessel - and gi intervened sprayed and he was momentarily better. Bled again dropped 4gm hgb and needed pressors and more blood - ir said can’t embolize, surgery was stating no proecedure due to potential mets from renal cancer near pancreas and that he would need a Whipple. Got family ready to say goodbye at least got the dni/dnr - and gave vitamin k (inr was 1.36 but why not he was dying) and transaxemic for the first instance in like years - more like a least we are doing something (gi also said why rescope - you can’t so quickly after spray?) - guy freakin lived and stopped bleeding! N=1 for sure and did a couple things and he has lived his life and did something likely safe (especially after reading your piece feel it likely is). The kicker - he was on prophylactic aspirin to prevent that first mace - at 88 and despite having cancer too.