Tranexamic acid in radical cystectomy: a systematic review and meta-analysis

Abstract

Background

Radical cystectomy is associated with substantial blood loss and transfusion requirements, raising the potential role of tranexamic acid (TXA) to mitigate these risks. However, its effectiveness and safety in this context remain to be fully established.

Methods

A comprehensive search of PubMed, Embase, Web of Science, and Scopus from inception to May 19, 2025, identified studies involving adult patients undergoing cystectomy (partial or radical) comparing TXA with placebo, no treatment, or alternative hemostatic agents.

Results

Four studies (1 RCT, 3 cohort studies) with sample sizes ranging from 64 to 936 patients were included. TXA significantly reduced estimated blood loss (SMD = –0.11; 95% CI: –0.21, –0.01; p = 0.03) and total transfusion volume (SMD = –0.28; 95% CI: –0.54, –0.02; p = 0.04). The odds of receiving any transfusion decreased by 52% (OR = 0.48; 95% CI: 0.30, 0.77; p = 0.002), with postoperative transfusion reduction particularly notable (OR = 0.32; 95% CI: 0.16, 0.63; p < 0.001). TXA showed no significant effect on intraoperative transfusion needs (OR = 0.95; p = 0.79) or perioperative hemoglobin change (SMD = 0.17; p = 0.08). Importantly, TXA did not increase VTE risk (OR = 1.49; p = 0.16) and was associated with a lower postoperative mortality in pooled analyses (OR = 0.62; 95% CI: 0.47, 0.82; p = 0.001).

Conclusions

Tranexamic acid appears effective in reducing blood loss and transfusion requirements during cystectomy, with no evidence of increased VTE risk and a potential survival benefit.

Introduction

Radical cystectomy (RC) is the gold standard treatment for muscle-invasive bladder cancer and certain cases of high-risk non-muscle invasive bladder cancer [1]. Despite recent improvements in surgical techniques, radical cystectomy causes significant intraoperative blood loss, and transfusion rates ranging from 30% to 60% [2]. This considerable blood loss and physiological stress can result in hemodynamic instability, increased risk of transfusion-related complications, prolonged hospital stay, and even higher postoperative morbidity and mortality [3].

Various strategies, including surgical dissection, the use of electrocautery and vessel-sealing devices, volume resuscitation with crystalloids, and the administration of allogeneic blood components such as packed red blood cells, fresh frozen plasma, and platelets, have been utilized to reduce intraoperative and postoperative bleeding. However, adverse effects such as transfusion-related acute lung injury (TRALI) [4], hemolytic reactions, immunosuppression, and increased postoperative infection rates have been reported [5]. In addition, blood transfusion has been associated with worse oncological outcomes in bladder cancer patients, after the radical cystectomy [6]. In recent years, antifibrinolytic agents such as tranexamic acid (TXA) have been considered as potential agents in reducing surgical blood loss and transfusion requirements. Tranexamic acid stabilizes blood clots, prevents the conversion of plasminogen to plasmin, and inhibits degradation of fibrin [7]. TXA has been widely used for controlling heavy menstrual bleeding, trauma-associated hemorrhage, and postpartum hemorrhage; and also reduced blood loss in various clinical settings such as cardiac, orthopedic, and gynecologic surgeries [7].

Despite the significant evidence supporting the use of TXA in major surgeries, its application in urologic oncology and radical cystectomy remains limited and controversial. Even though some studies suggest that intraoperative TXA administration during RC may reduce estimated blood loss and transfusion rates without significantly increasing thromboembolic complications [8], venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, has been reported in some articles studying traumatic TXA received patients [9]. Thus, the safety and efficacy of TXA in the setting of radical cystectomy require further investigations. Moreover, heterogeneity in dosing protocols and inclusion criteria among existing studies limits the generalizability of the findings. Additionally, patient populations vary in baseline comorbidities, tumor characteristics, and surgical approach (open vs. robotic-assisted), which can influence both bleeding risk and thrombotic events.

A comprehensive meta-analysis can evaluate the existing evidence on the use of tranexamic acid in radical cystectomy and investigate its impact on intraoperative blood loss, transfusion requirements, perioperative morbidity, length of hospital stay, and the incidence of thromboembolic complications. This systematic review will provide a clearer understanding of the potential benefits and risks of TXA employment in perioperative protocols for bladder cancer surgery and improve patient outcomes by optimizing hemostatic strategies in one of the most complex procedures in urologic oncology.

Method

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [10]. The protocol was registered in PROSPERO with the registration number: CRD420251061545

Eligibility criteria

Studies were eligible for inclusion if they involved adult patients undergoing cystectomy, regardless of surgical technique (partial or radical, open or minimally invasive), and they examined tranexamic acid administration via any route or dosage. Comparators included placebo, no treatment, or alternative hemostatic agents. Eligible studies reported at least one of the following outcomes: estimated blood loss, intraoperative transfusion, postoperative transfusion, total transfusion, mortality, hemoglobin change, or venous thromboembolism events such as pulmonary thromboembolism (PTE) and deep vein thrombosis (DVT). There were no restrictions on study design; however, case reports, letters to the editor, editorials, reviews, and studies lacking relevant outcomes were excluded.

Information sources and search strategy

A comprehensive search was conducted in PubMed (Embase), Web of Science (ISI), Scopus from inception to 19th May 2025, using combinations of keywords and MeSH terms related to the intervention and procedure of interest. The search terms included: (“Tranexamic Acid” OR tranexamic OR trane OR “tran exam” OR TXA OR “antifibrinolytic agents”) AND (“Radical Cystectomy” OR cystectomy OR cystectomies OR “bladder surgery” OR “bladder cancer surgery”), and the search was adapted for each database (Supplementary Table 1)

Study selection and data extraction

Two independent reviewers screened titles and abstracts for relevance. Full texts of potentially eligible studies were retrieved and assessed against the inclusion criteria. Discrepancies were resolved through discussion or by a third reviewer.

Data were extracted using a standardized form, including study characteristics (author, year, design, country), patient demographics, intervention details (dose, timing), and outcomes of interest. Authors were contacted for missing data when necessary.

The outcomes of this study are divided into two categories: primary outcomes, which include outcomes related to blood transfusion and bleeding, and secondary outcomes, which are related to post-surgical complications.

Risk of bias assessment

The Cochrane Risk of Bias 2.0 tool was used to assess RCTs, and the Newcastle Ottawa (NOS) [11] applied for Observational studies. Assessment was performed independently by two reviewers, and any disagreements were resolved through discussion or adjudicated by a third reviewer.

Data synthesis

Data synthesis was conducted using a random-effects meta-analysis model to account for potential heterogeneity across studies. Continuous outcomes such as hemoglobin change, blood loss, and transfusion volume were pooled using standardized mean differences (SMDs) with 95% confidence intervals. Dichotomous outcomes, including transfusion events, postoperative complications, mortality, and venous thromboembolism (VTE) were summarized using odds ratios (ORs) with 95% CIs.

Heterogeneity across studies was assessed using the I² statistic, τ², and Cochran’s Q test. An I² value greater than 50% was considered indicative of moderate to high heterogeneity. Where heterogeneity was present, potential sources were explored through subgroup analysis. Publication bias was not formally tested due to the limited number of studies per outcome.

All analyses were performed using a random-effects maximum likelihood (ML) model. Statistical significance was set at a two-sided p-value <0.05. Forest plots were generated to visualize individual and pooled effect sizes for each outcome.

Results

Following a systematic search, a total of 146 articles were identified and screened based on their titles and abstracts. Of these, 13 studies were selected for full-text assessment to evaluate eligibility. A total of 4 studies were included in the meta-analysis (Fig. 1), including both randomized controlled trials and cohort studies, which were published between 2016 and 2025. The sample size of the included studies ranged from 64 to 936 participants, including both women and men. Table 1 presents the characteristics of the included studies.

• A| Primary outcomes

• A.1| Estimated Blood Loss

Fig. 1.

PRISMA flow diagram.

Table 1.

Characteristics of included studies.

ID	Author	Year	Country	Study type	Population	Age	Female (%)	Sample size	Case (n)	Surgery	Dose	route of administration	duration of follow-up	QA
1	Egen, L [12]	2024	Germany	Cohort	Individuals undergoing RC	Case= 68 [10] Control= 72 [9]	Case= 16 Control= 34	64	32	Radical Cystectomy	1gr	Intravenous	30 days	9
2	Breau, R. H [13]	2024	Canada	RCT	Individuals undergoing RC for bladder cancer	Case= 69.43 (8.07) Control= 68.60 (10.17)	Case= 25.8 Control= 25.1	353	178	Open RC	10 mg/kg loading dose, followed by 5 mg/kg/h	Intravenous	30 days	low
3	Ahmed, M. E [14]	2025	USA	Cohort	Individuals undergoing RC for bladder cancer	Case= 68(8.18) Control= 65(8.92)	NR	936	468	RC	2 mg/kg/h	Intravenous	90 days	9
4	Zaid, H. B [15]	2016	USA	Cohort	Individuals undergoing open RC	Case= 68.33 Control= 10.38	Case= 11.7 Control= 19.5	303	103	Open RC	10 mg/kg loading dose, followed by 2 mg/kg/h	Intravenous	30 days	9
QA: Quality Assessment, RC: Radical Cystectomy

Pooled analysis demonstrated a statistically significant reduction in blood loss among patients receiving TXA compared to control (SMD = –0.11; 95% CI: –0.21, −0.01; p = 0.03). Heterogeneity was low (I² = 0%, τ² = 0.00, p = 0.39) (Fig. 2, Fig. 3).

• A.2| Hemoglobin Change

Fig. 2.

Forest Plots of the Effect of Tranexamic Acid on Blood Transfusion Rates in Cystectomy Patients. A) overall blood transfusion, B) Intraoperative blood transfusion, C) Postoperative blood transfusion.

Fig. 3.

Forest Plots of the Effect of Tranexamic Acid on Perioperative Blood Loss Outcomes in Cystectomy: A) Total and B) Intra/Postoperative Transfusion, C) Hemoglobin Change and D) Estimated Blood Loss.

Two studies reported perioperative hemoglobin change. The pooled estimate showed no statistically significant difference between TXA and control groups (SMD = 0.17; 95% CI: –0.02, 0.37; p = 0.08). Heterogeneity was absent (I² = 0%, p = 0.44), reflecting consistent findings.

• A.3| Total Transfusion Volume

Three studies evaluated total units of transfused blood. TXA was associated with a significant reduction in total transfusion volume (SMD = –0.28; 95% CI: –0.54, –0.02; p = 0.04). Heterogeneity was moderate (I² = 82.4%, τ² = 0.04). Moreover, four studies assessed transfusion as a binary outcome. TXA significantly reduced the odds of receiving any blood transfusion by 52% (OR = 0.48; 95% CI: 0.30, 0.77; p = 0.002). Heterogeneity was moderate (I² = 72.6%, τ² = 0.15), reflecting some variability among studies. Despite this, the effect remained robust and statistically significant.

• A.4| Intraoperative Blood Transfusion

Three studies showed no significant difference between TXA and control (OR = 0.95; 95% CI: 0.66, 1.38; p = 0.79; I² = 0%), indicating that TXA did not significantly affect transfusion needs during surgery. In addition, the pooled estimate showed a non-significant trend toward reduction (SMD = 0.14; 95% CI: –0.05, 0.34; p = 0.14; I² = 0%).

• A.5| Postoperative Blood Transfusion

Postoperative transfusion was significantly reduced in the TXA group, both in terms of risk (OR = 0.32; 95% CI: 0.16, 0.63; p < 0.001; I² = 0%) and volume (SMD = 0.54; 95% CI: 0.04, 1.03; p = 0.03; I² = 0%), suggesting a protective effect of TXA against delayed bleeding

• B| Secondary outcomes

• B.1|Mortality

Two studies reported postoperative mortality. The pooled OR favored TXA, with a statistically significant reduction (OR = 0.62; 95% CI: 0.47, 0.82; p = 0.001). No heterogeneity was observed (I² = 0%, p = 0.17), indicating consistent findings across studies (Fig. 4).

• B.2| Venous Thromboembolism (VTE)

Fig. 4.

Forest Plots of the Effect of Tranexamic Acid on Secondary Outcomes in Cystectomy: A) Mortality, B) VTE.

Four studies assessed the risk of VTE, including deep vein thrombosis and pulmonary embolism. Pooled analysis revealed no statistically significant increase in VTE risk in the TXA group (OR = 1.49; 95% CI: 0.86, 2.57; p = 0.16; I² = 0%). This suggests that TXA does not confer a heightened thrombotic risk in the context of cystectomy.

Quality assessment

The quality assessment of the included studies was evaluated using the Cochrane Risk of Bias and Newcastle Ottawa tool. Among the included studies, 1 was a randomized controlled trial, which was judged to have a low risk of bias. Other observational studies had a high quality. Detailed results of the quality assessment are presented in Supplementary Table 2.

Discussion

This systematic review and meta-analysis evaluated the efficacy and safety of TXA administration in patients undergoing radical cystectomy, a surgical procedure associated with considerable intraoperative and postoperative bleeding [16,17],. The findings of this study revealed that TXA injection before and during surgery significantly reduced the estimated bleeding rate (SMD = –0.11; 95% CI: –0.21, 0.01; p = 0.03). Moreover, the need for blood transfusions was generally lower in patients who received tranexamic acid (OR = 0.48; 95% CI: 0.30, 0.77; p = 0.002), with a more pronounced reduction observed in the postoperative period (OR = 0.32; 95% CI: 0.16, 0.63; p < 0.001). Several factors may explain why TXA was associated with a reduction in postoperative transfusion rates but not intraoperative transfusion rates. First, the antifibrinolytic effect of tranexamic acid may have a greater impact on postoperative bleeding than on intraoperative blood loss. Surgical bleeding during the procedure is often influenced by technical factors, extent of tissue dissection, and hemodynamic management, whereas postoperative bleeding is more closely related to ongoing fibrinolysis and microvascular oozing, processes that TXA is specifically designed to inhibit [18]. Second, intraoperative transfusion decisions are frequently guided by predefined institutional protocols, real-time hemodynamic status, and clinician judgment, which may reduce the ability to detect modest differences attributable to TXA. In contrast, postoperative transfusions are often administered in response to cumulative blood loss and postoperative hemoglobin decline, outcomes that may be more directly affected by the sustained antifibrinolytic action of TXA [19]. Third, the relatively low incidence of intraoperative transfusion events in several included studies may have limited the statistical power to detect significant differences between groups. Postoperative transfusions were generally more common and therefore may have provided greater sensitivity for identifying treatment effects. These findings are consistent with the known pharmacological mechanism of TXA, which inhibits fibrinolysis by blocking the activation of plasminogen by tissue-type plasminogen activator (tPA). TXA also reduces fibrin degradation by competitively inhibiting the binding of plasminogen and plasmin to fibrin, thereby stabilizing clot formation [20].

The results of this study are consistent with prior systematic reviews and clinical trials in other surgical settings, which have established TXA as an effective agent for reducing blood loss and transfusion rates [[21], [22], [23], [24]]. In orthopedic surgery, TXA administration reduced blood transfusion, blood loss, and Hb change [24]. Even in hip fracture surgery, characterized by a high risk of thrombosis, the use of local TXA was found to be associated with a significant reduction in blood transfusion and hemoglobin loss, without an increase in the incidence of thromboembolic events [21]. Similar trends have been reported in Otorhinolaryngologic surgeries [25,26], and gynecologic procedures [23,25,27],. Our findings are broadly consistent with those of Makabe et al. [28], as both analyses found no significant increase in VTE risk associated with TXA use, supporting its safety in radical cystectomy. However, our review provides a more comprehensive evaluation by examining additional outcomes, including estimated blood loss, total transfusion volume, perioperative hemoglobin change, intraoperative and postoperative transfusion requirements, and postoperative mortality. Unlike Makabe et al., who reported a non-significant reduction in perioperative transfusion risk, our analysis demonstrated significant reductions in estimated blood loss, total transfusion volume, and overall transfusion requirements. Furthermore, by separately assessing intraoperative and postoperative transfusions, we identified that the benefit of TXA was primarily driven by a reduction in postoperative transfusions. We also found a significant 38% reduction in postoperative mortality, an outcome not quantitatively synthesized in the previous review. Together, these findings extend the existing evidence by providing a more detailed assessment of the efficacy and safety of TXA in radical cystectomy.

Our findings align with those reported by Kim et al., who demonstrated that the administration of tranexamic acid significantly reduces estimated blood loss in various urologic procedures, including transurethral resection of the prostate (TURP), radical prostatectomy, and percutaneous nephrolithotomy [29]. Their study also identified significant reductions in hemoglobin change and transfusion rates among patients receiving tranexamic acid, supporting our results. However, in the present study, the association between tranexamic acid administration and hemoglobin change did not reach statistical significance, potentially due to the limited sample size.

Given that tranexamic acid is an anti-hemorrhagic agent, concerns have been raised regarding its potential to increase the risk of thrombotic events, such as pulmonary embolism or deep vein thrombosis. However, the findings of this study did not support this concern, demonstrating that tranexamic acid administration was not associated with a statistically significant increase in thromboembolic complications. This finding is consistent with the results reported by Kim et al., who found no significant association between tranexamic acid administration in urological surgeries and the occurrence of thromboembolic events [29]. In addition, no significant relationship was found in many studies that measured the effect of TXA on other surgeries’ outcomes [21,22,27,30],. However, careful patient selection is necessary, and caution should be exercised in individuals with a history of thromboembolic events or those with contraindications to antifibrinolytics.

In our study, TXA use was associated with lower postoperative mortality in pooled analyses; however, given the limited number of studies and the predominance of observational data, this finding should be considered exploratory and hypothesis-generating rather than evidence of a causal survival benefit. This suggests that TXA, by improving hemodynamic stability, reducing transfusion-related complications, and better controlling of perioperative bleeding, contributed to improved postoperative outcomes. This finding is in line with a study conducted by Arvind et al., which showed that mortality and morbidity rates in hysterectomy surgery were reduced after administration of TXA [31]. Adequately powered randomized controlled trials are required to determine whether the observed association reflects a true causal effect or is influenced by unmeasured confounding factors.

Limitation

This study has several limitations that should be considered when interpreting the findings. First, the included studies differed in design, comprising both randomized and observational studies, which may introduce variability related to patient selection, confounding control, and outcome ascertainment. Second, TXA dosing strategies varied across studies with respect to dose, timing of administration, and route of delivery, potentially affecting the magnitude of the antifibrinolytic effect. Third, differences in surgical approach, surgeon experience, and perioperative blood-conservation practices may have influenced baseline bleeding risk and transfusion requirements. Furthermore, transfusion thresholds and institutional transfusion protocols were not uniform across studies, which may have contributed to variability in transfusion-related outcomes independent of TXA administration. Finally, differences in perioperative management, including thromboprophylaxis regimens, fluid management strategies, and postoperative care pathways, may have affected both efficacy and safety outcomes. Additionally, formal assessment of publication bias was not feasible, raising the possibility that negative or null findings may be underrepresented. These factors underscore the need for further high-quality, prospective randomized controlled trials to confirm these findings and evaluate the long-term safety profile of tranexamic acid in this surgical context. Moreover, future studies should stratify outcomes based on surgical approach (open vs. minimally invasive), preoperative anticoagulant use, and patient-specific thrombotic risk, and economic evaluations examining the cost-effectiveness of TXA in RC are warranted, given the potential for significant reductions in transfusion-related costs.

Conclusion

In summary, this systematic review and meta-analysis demonstrate that tranexamic acid reduces perioperative blood loss and transfusion requirements in patients undergoing radical cystectomy without increasing the risk of venous thromboembolism. The consistent effect on postoperative transfusion highlights TXA’s utility as a hemostatic agent in urologic oncology. While further randomized trials are needed to confirm these findings and determine optimal protocols, current evidence supports the integration of TXA into perioperative management strategies for radical cystectomy.

Data availability statement

Not applicable.

Ethical approval

Not applicable.

Consent for publication

Not applicable.

Clinical trial number

Not applicable.

Consent to participate declaration

Not applicable.

Funding

This study did not receive funding, grant, or sponsorship from any individuals or organizations.

CRediT authorship contribution statement

Fatemeh Fereidooni: Writing – review & editing, Writing – original draft, Project administration, Data curation, Conceptualization. Masoud Dehbozorgi: Writing – review & editing, Writing – original draft, Supervision, Project administration, Methodology. Davoud Khalilzadeh Bonab: Writing – review & editing, Writing – original draft, Supervision, Project administration, Conceptualization. Arman Shafiee: Writing – review & editing, Writing – original draft, Supervision, Formal analysis, Data curation, Conceptualization. Fatemeh Mirhosseini: Writing – review & editing, Writing – original draft. Saba Goodarzi: Writing – review & editing, Writing – original draft, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.