Tranexamic Acid in Patients Undergoing Liver Resection: The HeLiX Randomized Clinical Trial
Tranexamic acid reduces bleeding and transfusion in range of surgical procedures, such as cardiac and orthopaedic surgery, however in cancer-related liver resection, mechanisms of bleeding and thrombotic risk factors differ.
The HeLiX (Hemorrhage During Liver Resection: Tranexamic Acid) trial was a multicentre, placebo-controlled, parallel, pragmatic randomised clinical trial that assessed the effect of tranexamic acid on bleeding, blood transfusion, and perioperative complications in patients undergoing liver resection for a cancer-related indication.
In this study, adult patients (aged ≥ 18 years) scheduled to undergo liver resection (open or minimally invasive) for a cancer-related indication (including colorectal liver metastases) were randomised in a 1:1 ratio to receive tranexamic acid (1 g bolus followed by 1 g infusion over 8 hours) or matching placebo (normal saline) following induction of anaesthesia and prior to surgical incision. The primary outcome was receipt of red cell transfusion from start of surgery until postoperative day 7, reported as the percentage of participants receiving transfusion. Transfusion guidelines were provided to participating sites, with the decision to transfuse left to the discretion of the medical teams.
A total of 3,768 patients were assessed for eligibility, with 1,245 participants included in the primary outcome analysis (tranexamic acid group, n = 619 versus placebo group, n = 626). With respect to the primary outcome, red cell transfusion within 7 days of surgery occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% of participants (n = 91) in the placebo group (odds ratio, 1.15 [95%CI,0.84-1.56]; P = .38; absolute difference, 2% [95%CI, −2% to 6%]). The measured intraoperative blood loss and the total estimated blood loss over 7 days were similar between groups, as was transfusion of other blood products and median number of red cell units transfused. Notably, participants in the tranexamic acid group experienced more perioperative complications compared with placebo (odds ratio, 1.28 [95%CI, 1.02-1.60]; P = .03). There was no significant difference in venous thromboembolism (odds ratio, 1.68 [95%CI, 0.95-3.07]; P = .08).
Overall, the findings from this study showed that in adult patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce blood transfusion within 7 days of surgery, intraoperative bleeding, or total blood loss over 7 days, with perioperative complications significantly more common in the tranexamic acid group.
Limitations of the trial include its ability to determine differences between specific complications postoperatively (heterogeneous in nature) and it lacked power to detect a difference in VTE rates or between sub-groups (including a subgroup who may have benefited from tranexamic acid). The authors highlight that an increase in complications observed in the current trial ‘warrants a cautious approach to adoption of tranexamic acid in surgical procedures in which it has not clearly been shown to be effective’.
The authors also note that it is ‘plausible that tranexamic acid is effective in areas of microvascular bleeding or general ooze but ineffective in areas in which bleeding occurs from major blood vessels’ (as it tends to be in liver resection, compared with many other surgical sites).
- Karanicolas PJ et al. Tranexamic Acid in Patients Undergoing Liver Resection: The HeLiX Randomized Clinical Trial. JAMA. Published online August 19, 2024. https://jamanetwork.com/journals/jama/article-abstract/2822555
