Tranexamic acid is associated with improved intestinal barrier function in traumatic hemorrhagic shock: A clinical prospective cohort study

Abstract

Tranexamic acid (TXA) is widely used as a hemostatic agent in emergency settings, particularly for traumatic hemorrhagic shock (THS) [1]. In 2010, the large-scale randomized controlled trial CRASH-2 demonstrated that TXA administration in patients with THS significantly reduced 28-day mortality, especially when given within 3 h post-injury [2]. However, clinical observations indicate that even after effectively controlling the primary cause of THS, many patients may still succumb to later complications, with intestinal source infections resulting from intestinal barrier dysfunction being a critical factor. This is because THS leads to decreased perfusion pressure, prompting selective vasoconstriction of the mesenteric arterioles to maintain perfusion of vital organs, but at the expense of intestinal ischemia [3].

Recent studies have shown that TXA, as a serine protease inhibitor, can protect the intestinal barrier during THS. In 2015, Diebel et al. [4] first observed in vitro that early infusion of TXA protects intestinal Caco-2 cells from ischemia-reperfusion injury, alleviating mucosal degradation following THS and promoting the recovery of intestinal barrier function. Furthermore, our group’s previous investigations have revealed significant upregulation of CitH3 and MPO expression in the gut following THS, indicating elevated inflammation levels and reduced expression of tight junction proteins. TXA has been shown to alleviate intestinal barrier damage by inhibiting neutrophil extracellular traps formation [5].

Despite these findings, there is a lack of clinical prospective studies focusing on TXA’s potential to improve intestinal barrier function. We therefore conducted a pilot prospective cohort study to evaluate the protective effects of TXA on the intestinal barrier in patients with THS. We prospectively observed and analyzed clinical data from a cohort of 61 patients with THS admitted to the Jinling hospital and Sir Run hospital affiliated to Nanjing Medical University between August 2021 and August 2022. Serial plasma samples were collected at multiple time points(DAY1, DAY3, DAY5, and DAY7). The detailed study design and methodology are available in the supplementary materials.We compared intestinal injury markers and clinical outcomes between the TXA treatment group (n = 33) and the control group (n = 28)(Suppl. Table 1).The baseline clinical and demographic characteristics were well balanced between the two groups, including age, time from injury to admission, injury causes and site, as well as injury severity scores(ISS, APACHE II, GCS, SOFA).

Extensive research has established that intestinal fatty acid-binding protein (I-FABP) and D-lactate (D-LA) serve as crucial markers for intestinal injury. The analysis revealed that the level of I-FABP significantly changed over time (P < 0.001). The mean I-FABP level in the TXA group was lower than that in the control group at all four time points, and the difference was significant on DAY 3 (P < 0.05). In addition, the treatment group was divided into early TXA (within 3 h post-injury, n = 19) and delayed TXA (over 3 h post-injury, n = 14) subgroups. The results showed that the level of I-FABP in the early TXA group was significantly lower than in the control group (P = 0.018), while there was no significant difference in the delayed TXA group (Fig. 1 A-C). The D-LA level increased to DAY 3 and reached its peak, and there was a significant difference between the groups at this time point. TXA treatment reduced the D-LA level (P = 0.032) (Fig. 1 D-F). Damage to the endothelial glycocalyx is another vascular injury associated with THS. Syndecan-1 (SDC-1) is a widely recognized marker of endothelial damage. The level of SDC-1 was significantly lower than that of the control group at DAY1 and DAY7 (P < 0.05), suggesting the protective effect of TXA on systemic vascular endothelium (Fig. 1 G-I). Abdullah et al. [6] found that glycocalyx damage after hemorrhagic shock is most severe in the lungs and intestines. Thus, although SDC-1 is not specific to the intestine, its elevated levels may partly indicate intestinal vascular injury due to the gut’s vulnerability to hypoperfusion and shock. TXA acts as a competitive inhibitor of plasminogen activation, thereby reducing fibrinolysis and stabilizing blood clots. In this study, patients treated with TXA showed higher fibrinogen levels and lower fibrin degradation products compared to controls, while other coagulation parameters such as platelet count, PT, APTT, and D-dimer showed no significant differences. These findings suggest that TXA effectively inhibits fibrinogen breakdown, contributing to improved clot stability and reduced blood loss, which is crucial for trauma patients(Suppl. Table 2). Enteral nutrition was identified as a confounding factor; however, in this pilot study with a small sample size, multivariable linear regression analysis adjusting for enteral nutrition did not alter the significant group differences in D-lactate (DAY3) and SDC1 (DAY1), while the IFABP result was affected but did not change our overall conclusions. TXA treatment did not yield significant results regarding clinical outcomes and related prognoses (such as blood transfusion rate, 28-day mortality rates, length of ICU stay, length of hospital), likely due to the limited sample size (Suppl. Table 3).

The pilot study provides evidence from a prospective cohort analysis suggesting that administration of TXA within three hours of injury has a protective effect on intestinal barrier function in patients with THS. The findings align with existing clinical research that emphasizes the hemostatic properties of TXA. Notably, early administration of TXA demonstrates a significant benefit in preserving intestine compared to delayed administration. However, the study also has several limitations. As a prospective cohort study conducted across two hospitals, there were instances of missing clinical data, which may have impacted the results. Additionally, the sample size was relatively small, highlighting the exploratory nature of this investigation. Future research with a larger sample size is necessary to further analyze the impact of TXA on intestinal barrier function. Including clinical symptom assessments related to gastrointestinal function or the application and compliance of enteral nutrition would also provide a more comprehensive evaluation of patient outcomes.

In summary, early application of TXA following THS was associated with lower plasma IFABP, D-LA, SDC-1, suggesting possible protective effects on intestinal barrier function and endothelial status. These findings support the necessity and importance of early TXA use in clinical practice for patients experiencing THS.

Fig. 1

The levels of intestinal injury and vascular endothelium indicators (I-FABP, D-LA, and SDC-1) decreased after TXA treatment. (A, D and G) Overall changes in I-FABP, D-LA and SDC-1 levels at different time points in THS patients; (B, E and H) TXA treatment reduces I-FABP, D-LA and SDC-1 levels compared with the control group; (C, F and I) Layered analysis of the changes in I-FABP, D-LA and SDC-1 levels at different time points in the early TXA group, delayed TXA group, and control group. (*P < 0.05, **P < 0.01, ***P<0.001, ns no significance)

Full size image

The datasets used and analyzed during the current study are available from the corresponding author in response to reasonable requests.

TXA:

Tranexamic acid

THS:

Traumatic hemorrhagic shock

I- FABP:

Intestinal fatty acid-binding protein

D-LA:

D-lactate

SDC-1:

Syndecan-1

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We are very grateful for the help and care provided by the staff of the department of emergency medicine, division of trauma and surgical intensive care unit, and clinical pathology and laboratory center at both Jinling Hospital and Sir Run Hospital affiliated with Nanjing Medical University.

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Authors and Affiliations

1. Division of Trauma and Surgical Intensive Care Unit, Department of Emergency Medicine, Jinling Hospital, School of Medicine, Southeast University, Nanjing, 210002, Jiangsu Province, P.R. China

   Fang Chen & Weiwei Ding

2. Division of Trauma and Surgical Intensive Care Unit, Department of Emergency Medicine, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, 210002, Jiangsu Province, P.R. China

   Chengnan Chu, Xinyu Wang & Weiwei Ding

3. Department of Emergency Medicine, Sir Run hospital affiliated to Nanjing medical university, Nanjing, 210002, Jiangsu Province, P.R. China

   Qianjin Shen & Danbing Shao

4. Laboratory Center, Sir Run hospital affiliated to Nanjing medical university, Nanjing, 210002, Jiangsu Province, P.R. China

   Anfang Wang

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Contributions

FC and WD contributed in the literature search. FC, CC, XW and WD contributed in the study design. FC, QS and AW contributed in the data collection. FC, QS and CC contributed in the data analysis. FC, CC, XW, DS and WD contributed in the data interpretation. FC, XW and WD contributed in the writing of the article. FC, DS and WD contributed in the critical revision.

Corresponding author

Correspondence to Weiwei Ding.

Ethics approval and consent to participate

The Institutional Review Board of Jinling hospital and Sir Run hospital affiliated to Nanjing medical university approved the clinical trial (2021NZKY-043-01), which was registered online (chictr.org.cn) (ChiCTR2000032407).

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Not applicable.

Competing interests

The authors declare no competing interests.

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Chen, F., Chu, C., Wang, X. et al. Tranexamic acid is associated with improved intestinal barrier function in traumatic hemorrhagic shock: A clinical prospective cohort study. Crit Care 29, 353 (2025). https://doi.org/10.1186/s13054-025-05605-2

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• Received: 11 June 2025

• Accepted: 05 August 2025

• Published: 12 August 2025

• DOI: https://doi.org/10.1186/s13054-025-05605-2

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