Liver and Bile
Hepatology. 2024;80(2):376–88
Tranexamic acid in upper gastrointestinal bleed in patients with cirrhosis: A randomized controlled trial
Background and aims: Patients with Child-Turcotte-Pugh class B and C cirrhosis with upper gastrointestinal bleeding (UGIB) have systemic as well as localized (in the mucosa of the esophagus and stomach) fibrinolysis. The aim of this study was to evaluate the efficacy and safety of tranexamic acid in the treatment of acute UGIB in patients with cirrhosis. Approach and results: A total of 600 patients with advanced liver cirrhosis (Child-Turcotte-Pugh class B or C) presenting with UGIB were randomly allocated to either the tranexamic acid (n = 300) or the placebo group (n = 300). The primary outcome measure was the proportion of patients developing 5-day treatment failure. Failure to control bleeding by day 5 was seen in 19/300 (6.3%) patients in the tranexamic acid group and 40/300 (13.3%) patients in the placebo group (p = 0.006). Esophageal endoscopic variceal ligation (EVL) site as a source of failure to control bleeding by day 5 among patients undergoing first-time esophageal EVL (excluding patients with a previous post-EVL ulcer as a source of bleed) was seen in 11/222 (4.9%) patients in the tranexamic acid group and 27/225 (12.0%) patients in the placebo group (p = 0.005). However, 5-day and 6-week mortality was similar in the tranexamic acid and placebo groups.
Conclusions: Tranexamic acid significantly reduces the failure to control bleeding by day 5 and failure to prevent rebleeding after day 5 to 6 weeks in patients with advanced liver cirrhosis (Child-Turcotte-Pugh class B or C) presenting with upper gastrointestinal bleeding, by preventing bleeding from the endoscopic variceal ligation site.
DOI: 10.1097/hep.0000000000000817
PD Dr. Michael Schultheiß
Head of the Interdisciplinary Ultrasound Center and Clinical Head of the TIPS Section, Department of Internal Medicine II, University Medical Center Freiburg (Germany)
Should tranexamic acid be included in the therapeutic algorithm for variceal bleeding?
Patients with liver cirrhosis frequently experience gastrointestinal bleeding. Although the summary of product characteristics (SMPC) for tranexamic acid injectable solution lists „gastrointestinal bleeding“ as a potential indication, there is limited data on its use in patients with liver cirrhosis. The recent study by Kumar et al. addresses this gap by evaluating tranexamic acid in patients with upper gastrointestinal bleeding and Child-Pugh class B and C liver cirrhosis, providing significant insights into its potential clinical utility.
The study outcomes, while encouraging, align with existing expectations. In the tranexamic acid group, higher and statistically significant bleeding control was achieved by day 5 (6.3% vs. 13.3%; p = 0.006) and after day 5 (12% vs. 21.3%; p = 0.002). One study focus was on variceal bleeding, which was the cause of bleeding in > 85% in both groups. Patients experiencing rebleeding from esophageal endoscopic variceal ligation (EVL) sites also benefited from the use of tranexamic acid by day 5 (4.9% vs. 12%; p = 0.005) and after day 5 (8.5% vs. 16.4%; p = 0.007). However, no statistically significant survival benefit was achieved with tranexamic acid over a follow-up period of up to 6 weeks.
Despite the clinical relevance of these findings, the study has several obvious weaknesses. The fact that liver cirrhosis disproportionately affects men in India as well, where the study was conducted, is understandable; however, the nearly 9:1 male-to-female ratio is astonishing. In addition, very few of the patients in either group underwent preemptive transjugular intrahepatic portosystemic shunt (TIPS; 1.6% and 1.3%) – despite Baveno guidelines recommending TIPS for variceal bleeding in this particular patient cohort. It would be interesting to evaluate the risk of TIPS occlusions due to thrombosis in the context of tranexamic acid use. It is also notable that while portal vein thrombosis (PVT) was an exclusion criterion, a significant percentage of patients with hepatocellular carcinoma (HCC) and malignant PVT were included (7% and 9%, respectively).
Prokinetics, antibiotics, and vasoactive drugs are essential medications for treating patients with liver cirrhosis and variceal bleeding. Further studies are required to determine whether tranexamic acid should be considered a similarly essential therapeutic in this setting.