Efficacy and safety of tranexamic acid in non-haemophilia bleeding disorders: A systematic review of randomized controlled trials

Abstract BACKGROUND Tranexamic acid (TXA) is a synthetic antifibrinolytic agent widely used to reduce bleeding in surgical procedures, trauma, and bleeding disorders. While its efficacy is well-documented in hemophilic patients and perioperative bleeding, data on its use in non-hemophilic bleeding, such as von Willebrand disease, platelet function disorders, HHT and other inherited or acquired coagulopathies– are comparatively limited. Objectives To systematically evaluate the efficacy and safety of TXA compared to placebo or standard care in patients with non-hemophilia bleeding disorders using evidence from randomized controlled trials (RCTs). Methods A comprehensive searches of PubMed, Embase, CENTRAL and clinicaltrial.gov were performed through June 2025. Eligible studies were randomised controlled trials (RCTs) comparing TXA (oral, intravenous, or topical) to placebo or standard care in patients with non-haemophilia bleeding disorders. After deduplication, 645 records were screened using Rayyan software by two independent reviewers. Eligible studies reported on bleeding outcomes such as menstrual blood loss or epistaxis frequency and safety measures and quality of life (QoL). Risk of bias was assessed independently using the Cochrane RoB 2.0 tool. Due to limited trial numbers and heterogeneity, results were synthesized narratively. Results Out of 645 studies, two RCTs (n=69 patients receiving TXA) met the inclusion criteria. In a phase 3 crossover RCT of 36 women with mild to moderate von Willebrand disease (vWF) and heavy menstrual bleeding, TXA significantly reduced menstrual blood loss compared to recombinant von Willebrand factor (rVWF): mean PBAC score 110.5 vs. 180.4 (mean difference: -69.9, p< 0.0001). No significant differences were found in QoL measures. Rescue use of rVWF did not provide added bleeding reduction (PBAC 308 vs 267; p= 0.591). In a parallel-arm RCT of 121 patients with hereditary hemorrhagic telangiectasis (HHT), 33 participants received topical intranasal TXA. After 12 weeks, the median weekly epistaxis frequency was 7.5 (IQR: 3.0-11.0) with TXA vs. 8.0 (IQR: 3.0-14.0) with placebo (p= 0.97), indicating no statistically significant difference. Secondary outcomes, including epistaxis severity and QoL, were also not significantly different between groups. Both studies reported no thromboembolic events. Mild adverse events (e.g., gastrointestinal discomfort, nasal irritation) were self-limited. Conclusion TXA exhibits encouraging but preliminary evidence of safety and effectiveness in non hemophilic bleeding disorders. TXA is well tolerated and considerably lowers menstrual blood loss in patients with vWF. Its usefulness in managing epistaxis in patients with hereditary hemorrhagic telangiectasia, however, seems to be limited. While recent trials show good safety results and no thromboembolic events, the body of evidence is still small, inconsistent, and condition-specific. In order to more clearly define the therapeutic role, best use, and long-term safety of TXA across a wider range of non-hemophilic bleeding disorders, larger, methodologically rigorous randomized controlled trials are required.