Clinical Trial

. 2024 Oct 1;332(13):1080-1089.

doi: 10.1001/jama.2024.11783.

Tranexamic Acid in Patients Undergoing Liver Resection: The HeLiX Randomized Clinical Trial

Paul J Karanicolas^{1

2

3}, Yulia Lin^{4

5}, Stuart A McCluskey^{6

7}, Jordan Tarshis⁸, Kevin E Thorpe⁹, Alice Wei¹⁰, Elijah Dixon^{11

12}, Geoff Porter^{13

14}, Prosanto Chaudhury^{15

16}, Sulaiman Nanji^{17

18}, Leyo Ruo^{19

20}, Melanie E Tsang^{2

21

22}, Anton Skaro^{23

24}, Gareth Eeson^{25

26}, Sean Cleary^{2

27}, Carol-Anne Moulton^{2

27}, Chad G Ball^{11

12}, Julie Hallet^{1

2

3}, Natalie Coburn^{1

2

3}, Pablo E Serrano^{20

28}, Shiva Jayaraman^{2

21

22}, Calvin Law^{1

2

3}, Ved Tandan^{19

20}, Gonzalo Sapisochin^{2

27}, David Nagorney²⁹, Douglas Quan^{23

24}, Rory Smoot²⁹, Steven Gallinger^{2

27}, Peter Metrakos^{15

16}, Trevor W Reichman^{2

27}, Diederick Jalink^{17

18}, Sean Bennett^{17

30}, Francis Sutherland^{11

12}, Edward Solano²⁵, Michele Molinari^{13

31}, Ephraim S Tang^{23

24}, Susanne G Warner²⁹, Oliver F Bathe³², Jeffrey Barkun^{15

16}, Michael L Kendrick²⁹, Mark Truty²⁹, Rachel Roke³, Grace Xu³, Myriam Lafreniere-Roula³³, Gordon Guyatt^{34

35}; HPB CONCEPT Team

Affiliations

¹ Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
² Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
³ Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
⁴ Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
⁵ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Anesthesia and Pain Management, University Health Network, Toronto, Ontario, Canada.
⁷ Department of Anesthesia and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Anesthesia, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
⁹ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Memorial Sloan Kettering Cancer Center, New York, New York.
¹¹ Foothills Medical Centre, Calgary, Alberta, Canada.
¹² Department of Surgery, University of Calgary, Calgary, Alberta, Canada.
¹³ Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
¹⁴ Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
¹⁵ McGill University Health Centre, Montreal, Quebec, Canada.
¹⁶ Department of Surgery, McGill University, Montreal, Quebec, Canada.
¹⁷ Department of Surgery, Queen's University, Kingston, Ontario, Canada.
¹⁸ Kingston Health Sciences Centre, Kingston, Ontario, Canada.
¹⁹ Juravinski Hospital, Hamilton, Ontario, Canada.
²⁰ Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
²¹ Department of Surgery, Unity Health Toronto-St Joseph's Health Centre, Toronto, Ontario, Canada.
²² Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada.
²³ London Health Sciences Centre, London, Ontario, Canada.
²⁴ Department of Surgery, Western University, London, Ontario, Canada.
²⁵ Kelowna General Hospital, Kelowna, British Columbia, Canada.
²⁶ Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
²⁷ University Health Network, Toronto, Ontario, Canada.
²⁸ Department of Surgery, Juravinski Hospital, Hamilton, Ontario, Canada.
²⁹ Department of Surgery, Mayo Clinic, Rochester, Minnesota.
³⁰ Department of Surgery, Kingston Health Sciences Centre, Kingston, Ontario, Canada.
³¹ Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
³² Department of Surgery and Oncology, University of Calgary, Calgary, Alberta, Canada.
³³ Unity Health Toronto, Toronto, Ontario, Canada.
³⁴ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
³⁵ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

PMID: 39158894
PMCID: PMC11334013
DOI: 10.1001/jama.2024.11783

Clinical Trial

Tranexamic Acid in Patients Undergoing Liver Resection: The HeLiX Randomized Clinical Trial

Paul J Karanicolas et al. JAMA. 2024.

. 2024 Oct 1;332(13):1080-1089.

doi: 10.1001/jama.2024.11783.

Authors

Affiliations

¹ Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
² Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
³ Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
⁴ Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
⁵ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁶ Department of Anesthesia and Pain Management, University Health Network, Toronto, Ontario, Canada.
⁷ Department of Anesthesia and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Anesthesia, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
⁹ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Memorial Sloan Kettering Cancer Center, New York, New York.
¹¹ Foothills Medical Centre, Calgary, Alberta, Canada.
¹² Department of Surgery, University of Calgary, Calgary, Alberta, Canada.
¹³ Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
¹⁴ Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
¹⁵ McGill University Health Centre, Montreal, Quebec, Canada.
¹⁶ Department of Surgery, McGill University, Montreal, Quebec, Canada.
¹⁷ Department of Surgery, Queen's University, Kingston, Ontario, Canada.
¹⁸ Kingston Health Sciences Centre, Kingston, Ontario, Canada.
¹⁹ Juravinski Hospital, Hamilton, Ontario, Canada.
²⁰ Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
²¹ Department of Surgery, Unity Health Toronto-St Joseph's Health Centre, Toronto, Ontario, Canada.
²² Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada.
²³ London Health Sciences Centre, London, Ontario, Canada.
²⁴ Department of Surgery, Western University, London, Ontario, Canada.
²⁵ Kelowna General Hospital, Kelowna, British Columbia, Canada.
²⁶ Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
²⁷ University Health Network, Toronto, Ontario, Canada.
²⁸ Department of Surgery, Juravinski Hospital, Hamilton, Ontario, Canada.
²⁹ Department of Surgery, Mayo Clinic, Rochester, Minnesota.
³⁰ Department of Surgery, Kingston Health Sciences Centre, Kingston, Ontario, Canada.
³¹ Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
³² Department of Surgery and Oncology, University of Calgary, Calgary, Alberta, Canada.
³³ Unity Health Toronto, Toronto, Ontario, Canada.
³⁴ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
³⁵ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

PMID: 39158894
PMCID: PMC11334013
DOI: 10.1001/jama.2024.11783

Abstract

Importance: Tranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear.

Objective: To determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection.

Design, setting, and participants: Multicenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization.

Interventions: Tranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia.

Main outcomes and measures: The primary outcome was receipt of red blood cell transfusion within 7 days of surgery.

Results: 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. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (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%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08).

Conclusions and relevance: Among patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications.

Trial registration: ClinicalTrials.gov Identifier: NCT02261415.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Lin reported receipt of grants from Canadian Blood Services and Octapharma and personal fees from Choosing Wisely Canada. Dr Wei reported receipt of personal fees from Histosonics and grants from Ipsen. Dr Chaudhury reported receipt of honoraria for participation in advisory boards from AstraZeneca, Merck, and Paladin. Dr Serrano reported receipt of consulting fees from Incyte Biosciences Canada and Hoffmann–La Roche. Dr Law reported receipt of personal fees from Ipsen Canada and Amgen Canada. Dr Sapisochin reported receipt of personal fees from AstraZeneca, Roche, Integra, HepaRegeniX, Natera, and Eisai and research support from AstraZeneca, Roche, Stryker, and Natera. Dr Reichman reported receipt of clinical trial support from Vertex Pharmaceuticals. No other disclosures were reported.

Figures

**Figure 1.. Flow of Participants Through the HeLiX Trial**
^aOther reasons included participation in another study and/or scheduling problems. ^bParticipants may have undergone laparotomy with or without biopsy and/or resection of a different organ.

**Figure 2.. Subgroup-Specific Odds Ratios of Treatment Effects**
Risk differences are expressed in proportions.

See this image and copyright information in PMC

Comment in

The value of tranexamic acid in liver resection should not be exaggerated or ignored.
Ge P, Wu Y. Ge P, et al. Hepatobiliary Surg Nutr. 2025 Aug 1;14(4):689-691. doi: 10.21037/hbsn-2025-502. Epub 2025 Jul 24. Hepatobiliary Surg Nutr. 2025. PMID: 40893751 Free PMC article. No abstract available.

References

1. Dhar VK, Wima K, Lee TC, et al. Perioperative blood transfusions following hepatic lobectomy: a national analysis of academic medical centers in the modern era. HPB (Oxford). 2019;21(6):748-756. doi: 10.1016/j.hpb.2018.10.022 - DOI - PubMed
1. Kim S, Jung YK, Lee KG, et al. A systematic review and meta-analysis of blood transfusion rates during liver resection by country. Ann Surg Treat Res. 2023;105(6):404-416. doi: 10.4174/astr.2023.105.6.404 - DOI - PMC - PubMed
1. Bui LL, Smith AJ, Bercovici M, Szalai JP, Hanna SS. Minimising blood loss and transfusion requirements in hepatic resection. HPB (Oxford). 2002;4(1):5-10. doi: 10.1080/136518202753598672 - DOI - PMC - PubMed
1. Katz SC, Shia J, Liau KH, et al. Operative blood loss independently predicts recurrence and survival after resection of hepatocellular carcinoma. Ann Surg. 2009;249(4):617-623. doi: 10.1097/SLA.0b013e31819ed22f - DOI - PubMed
1. Kusano T, Sasaki A, Kai S, et al. Predictors and prognostic significance of operative complications in patients with hepatocellular carcinoma who underwent hepatic resection. Eur J Surg Oncol. 2009;35(11):1179-1185. doi: 10.1016/j.ejso.2009.04.008 - DOI - PubMed

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Tranexamic Acid in Patients Undergoing Liver Resection: The HeLiX Randomized Clinical Trial

Affiliations

Tranexamic Acid in Patients Undergoing Liver Resection: The HeLiX Randomized Clinical Trial

Authors

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Abstract

Conflict of interest statement

Figures

Comment in

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Publication types

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Associated data

Grants and funding

LinkOut - more resources

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