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A comprehensive meta-analysis of 6,976 patients confirms that prophylactic tranexamic acid (TXA) reduces the risk of major bleeding by 28% and the need for blood transfusions by 25% across general surgical procedures.
Crucially, the administration of TXA was not associated with a statistically significant increase in venous thromboembolism (VTE) or overall mortality, addressing a long-standing safety concern in non-cardiac surgery.
Subgroup analyses reveal significant heterogeneity in efficacy; while hepatobiliary surgeries showed clear benefits in reducing major bleeding, the advantages were less pronounced in general abdominal procedures.
Background: The Evolution of TXA in Perioperative Care
Tranexamic acid (TXA), a synthetic derivative of the amino acid lysine, has long been a cornerstone in the management of trauma-induced hemorrhage and blood loss in orthopedic and cardiac surgeries. By competitively inhibiting the activation of plasminogen to plasmin, TXA effectively stabilizes fibrin clots and mitigates hyperfibrinolysis. However, its adoption in general surgery—a broad field encompassing everything from minor abdominal wall repairs to complex visceral resections—has been slower and more controversial.
The primary hesitation among surgeons and anesthesiologists has been twofold: the uncertainty regarding its actual efficacy in elective abdominal procedures where bleeding may be less predictable, and the theoretical risk of inducing a pro-thrombotic state. Given the high-stakes nature of perioperative care, clinicians require robust, evidence-based data to justify the routine use of TXA. The recent study by Delgado et al., published in JAMA Surgery, seeks to provide this clarity by synthesizing the current body of randomized controlled trial (RCT) evidence.
Study Design: A Methodological Overview
This systematic review and meta-analysis involved a rigorous search of PubMed, Embase, and the Cochrane Library, covering data from inception through early April 2025. The researchers focused exclusively on RCTs that compared prophylactic TXA against placebos in adult patients undergoing general surgery.
A total of 26 RCTs, encompassing 6,976 patients, met the inclusion criteria. The primary endpoints analyzed were intraoperative blood loss, the requirement for blood transfusions, and the incidence of major bleeding. Safety endpoints included mortality and the occurrence of venous thromboembolic events (VTE), such as deep vein thrombosis and pulmonary embolism. Data synthesis utilized random-effects models to account for potential variations in study populations and surgical techniques.
Key Findings: Efficacy and Safety Profile
Intraoperative Blood Loss and Transfusion Requirements
The meta-analysis demonstrated that TXA use was associated with a statistically significant reduction in intraoperative blood loss, with a mean difference (MD) of -35.85 mL (95% CI, -57.20 to -14.51 mL; P = .001). While the absolute volume reduction appears modest, the impact on transfusion requirements was more clinically substantial. Patients receiving TXA had a 25% lower risk of needing a blood transfusion compared to those in the placebo group (RR, 0.75; 95% CI, 0.60-0.94; P = .01).
Major Bleeding and Safety Endpoints
One of the most compelling findings was the reduction in major bleeding events. TXA was associated with a 28% reduction in the risk of major hemorrhage (RR, 0.72; 95% CI, 0.59-0.89; P = .002). This result was remarkably consistent across studies, as indicated by an I2 statistic of 0%, suggesting low heterogeneity for this specific outcome.
From a safety perspective, the data were reassuring. There was no significant difference in the risk of VTE (RR, 1.09; 95% CI, 0.62-1.92; P = .75) or mortality (RR, 1.08; 95% CI, 0.72-1.61; P = .71) between the groups. Furthermore, TXA did not significantly impact the length of hospital stay (MD, -0.54 days; P = .08), though a slight trend toward shorter stays was noted.
The Nuance of Subgroup Analysis: Abdominal vs. Hepatobiliary
The study provides essential insights through subgroup analysis, suggesting that the benefits of TXA are not uniform across all types of general surgery. In the subgroup restricted to abdominal procedures, the overall benefits seen in blood loss and transfusion needs were no longer statistically significant. This suggests that in standard abdominal surgeries—where bleeding is often controlled through direct visualization and cautery—the incremental benefit of systemic TXA may be minimal.
In contrast, the hepatobiliary subgroup showed a distinct advantage. In these often highly vascular and complex procedures, TXA was associated with a significant reduction in major bleeding (RR, 0.59; 95% CI, 0.39-0.90; P = .01). This finding aligns with the biological understanding of the liver’s role in coagulation and the high risk of fibrinolysis during hepatic resection.
Clinical Implications and Expert Commentary
The findings by Delgado et al. support the integration of TXA into the perioperative toolkit for general surgery, but with a caveat of clinical judgment. The high heterogeneity (I2 = 91%) observed in the intraoperative blood loss data suggests that the surgical context matters immensely. Factors such as the patient’s baseline coagulation status, the specific surgical technique (e.g., laparoscopic vs. open), and the inherent vascularity of the target organ must be considered.
Expert clinicians suggest that while TXA is safe, its routine use in low-risk abdominal procedures might not be necessary. However, in cases where significant blood loss is anticipated or in patients with borderline hemoglobin levels where avoiding a transfusion is a priority, TXA offers a low-cost, high-safety intervention. The lack of increased VTE risk is particularly important, as it may alleviate the concerns of surgeons who have historically been hesitant to use antifibrinolytics in patients with cancer or other pro-thrombotic risk factors.
Conclusion: Moving Toward Precision Prophylaxis
This systematic review and meta-analysis provide strong evidence that prophylactic TXA is an effective and safe strategy for reducing bleeding complications in general surgery. The reduction in major bleeding and transfusion requirements represents a significant improvement in patient outcomes and a potential reduction in healthcare costs associated with blood products.
Ultimately, the decision to administer TXA should be individualized. As the surgical community moves toward more personalized medicine, the focus should shift from ‘should we use TXA?’ to ‘for which patient and which procedure is TXA most beneficial?’ Future research should aim to define optimal dosing strategies and identify specific patient biomarkers that predict a superior response to antifibrinolytic therapy.
References
Delgado LM, Pompeu BF, Martins GHA, Azevedo ML, Pasqualotto E, Chulam TC, de Figueiredo SMP. Perioperative Use of Tranexamic Acid in General Surgery: A Systematic Review and Meta-Analysis. JAMA Surg. 2025 Dec 17:e255498. doi: 10.1001/jamasurg.2025.5498. Epub ahead of print. PMID: 41405985; PMCID: PMC12712826.