Tranexamic Acid Increases Complications Without Reducing Blood Transfusions in Liver Resection, HeLiX Trial Finds

The study, published in JAMA, revealed that tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications among patients undergoing liver resection for a cancer-related indication.

"Within seven days of surgery, 16.3% of participants who received tranexamic acid required red blood cell (RBC) transfusions, compared to 14.5% of those who received a placebo. Additionally, the group treated with tranexamic acid experienced notably higher rates of perioperative complications compared to the placebo group, with an odds ratio of 1.28 indicating a significantly increased risk," the researchers reported.

Tranexamic acid is known for its antifibrinolytic properties, which help prevent excessive bleeding by inhibiting the breakdown of blood clots. It is known to reduce bleeding and the need for blood transfusions in various types of surgery, but its effectiveness in patients undergoing liver resection for cancer-related conditions remains uncertain. To fill this knowledge gap, Paul J. Karanicolas, Department of Surgery, University of Toronto, Toronto, Ontario, Canada, and colleagues aimed to investigate whether tranexamic acid reduces RBC transfusion within 7 days of liver resection.

For this purpose, the researchers conducted a multicenter randomized clinical trial from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and one site in the United States, with a 90-day follow-up. The study included a volunteer sample of 1,384 patients undergoing liver resection for cancer-related conditions, who met eligibility criteria and consented to randomization. Participants, clinicians, and data collectors were blinded to the treatment allocation.

The trial compared the effects of tranexamic acid, administered as a 1-gram bolus followed by a 1-gram infusion over 8 hours, with a matching placebo. 619 participants received tranexamic acid, while 626 received the placebo, starting at the anesthesia induction.

The primary outcome measure was the incidence of red blood cell transfusion within seven days of surgery.

The study revealed the following findings:

• The primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases).
• Perioperative characteristics were similar between groups.
• RBC transfusion occurred in 16.3% of participants in the tranexamic acid group and 14.5% in the placebo group (odds ratio, 1.15).
• Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL) and total estimated blood loss over seven days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL) were similar between groups.
• Participants receiving tranexamic acid experienced significantly more complications than placebo (odds ratio, 1.28), with no significant difference in venous thromboembolism (odds ratio, 1.68).

Other trials that found no impact of tranexamic acid on RBC transfusion suggest that varying sources of bleeding may explain the differing results observed in previous studies. For example, the HALT-IT trial, which included 12,009 patients with acute gastrointestinal bleeding, found no effect of TXA on bleeding-related mortality. Additionally, a recent trial evaluating prophylactic TXA to prevent obstetrical hemorrhage following Cesarean delivery revealed no significant impact on maternal death or the need for blood transfusion.

Reference:

Karanicolas PJ, Lin Y, McCluskey SA, et al. Tranexamic Acid in Patients Undergoing Liver Resection: The HeLiX Randomized Clinical Trial. JAMA. Published online August 19, 2024. doi:10.1001/jama.2024.11783