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.

Tranexamic acid for prevention of surgical bleeding: Review

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.

Since 2022, major UK surgical and anesthesia societies have called for routine consideration of tranexamic acid in most adult inpatient surgeries.

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.

References

Park LJ, Marcucci M, Ofori SN, Borges FK, Nenshi R, Kanstrup CTB, Rosen M, Landoni G, Lomivorotov V, Painter TW, Xavier D, Martinez-Zapata MJ, Szczeklik W, Meyhoff CS, Chan MTV, Simunovic M, Bogach J, Serrano PE, Balasubramanian K, Cadeddu M, Yang I, Kim WH, Devereaux PJ. Safety and Efficacy of Tranexamic Acid in General Surgery. JAMA Surg. 2025 Mar 1;160(3):267-274. doi: 10.1001/jamasurg.2024.6048. PMID: 39813061; PMCID: PMC11904705.

Tsan SEH, Viknaswaran NL, Cheong CC, Cheah S, Ng KT, Mong SXY, Wang CY. Prophylactic intravenous tranexamic acid and thromboembolism in non-cardiac surgery: a systematic review, meta-analysis and trial sequential analysis. Anaesthesia. 2023 Sep;78(9):1153-1161. doi: 10.1111/anae.16058. Epub 2023 Jun 14. PMID: 37314744.