Meta-Analysis

. 2025 Nov;135(5):1172-1192.

doi: 10.1016/j.bja.2025.07.079. Epub 2025 Sep 12.

Use of prothrombin complex concentrates in liver transplantation: a systematic review and meta-analysis

Isabella Kojundzic¹, Neeki Alavi², Austin Lam², Keyvan Karkouti³, Jeannie Callum⁴, Matthanja Bieze⁵, Carla Luzzi⁶, Chaya Shwaartz⁷, Marina Englesakis⁸, François Martin Carrier⁹, Jan-Willem Boldingh¹⁰, Jaap-Jan Vos¹⁰, Johannes P van den Berg¹⁰, Klaus Görlinger¹¹, Christopher Harle¹², Adrienne Carr¹³, Ton Lisman¹⁴, Wilton A van Klei¹⁵, Stuart A McCluskey¹⁶, Justyna Bartoszko¹⁷

Affiliations

¹ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; University of Ottawa Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
² Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada.
³ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁴ Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada; Sunnybrook Research Institute, Toronto, Ontario, Canada.
⁵ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Erasmus Medical Centre, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁶ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁷ Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada.
⁸ Library & Information Services, University Health Network, Toronto, ON, Canada.
⁹ Department of Anaesthesiology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada.
¹⁰ Department of Anaesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹¹ Department of Anaesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany; Tem Innovations, Munich, Germany.
¹² Department of Anaesthesia and Perioperative Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
¹³ Department of Anaesthesia, Pain Management, and Perioperative Medicine, Dalhousie University, Nova Scotia, Canada.
¹⁴ Faculty of Medical Sciences, University of Groningen, Groningen, The Netherlands; Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁵ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology, Intensive Care and Emergency Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁶ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
¹⁷ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada. Electronic address: justyna.bartoszko@uhn.ca.

PMID: 40945996
PMCID: PMC12597362
DOI: 10.1016/j.bja.2025.07.079

Meta-Analysis

Use of prothrombin complex concentrates in liver transplantation: a systematic review and meta-analysis

Isabella Kojundzic et al. Br J Anaesth. 2025 Nov.

. 2025 Nov;135(5):1172-1192.

doi: 10.1016/j.bja.2025.07.079. Epub 2025 Sep 12.

Authors

Affiliations

¹ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; University of Ottawa Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
² Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada.
³ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁴ Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada; Sunnybrook Research Institute, Toronto, Ontario, Canada.
⁵ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Erasmus Medical Centre, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁶ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁷ Ajmera Transplant Centre, Toronto General Hospital, University Health Network, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada.
⁸ Library & Information Services, University Health Network, Toronto, ON, Canada.
⁹ Department of Anaesthesiology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada.
¹⁰ Department of Anaesthesiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹¹ Department of Anaesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany; Tem Innovations, Munich, Germany.
¹² Department of Anaesthesia and Perioperative Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
¹³ Department of Anaesthesia, Pain Management, and Perioperative Medicine, Dalhousie University, Nova Scotia, Canada.
¹⁴ Faculty of Medical Sciences, University of Groningen, Groningen, The Netherlands; Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁵ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology, Intensive Care and Emergency Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁶ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
¹⁷ Department of Anaesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada; Department of Anaesthesiology and Pain Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada. Electronic address: justyna.bartoszko@uhn.ca.

PMID: 40945996
PMCID: PMC12597362
DOI: 10.1016/j.bja.2025.07.079

Abstract

Background: Liver transplantation (LT) can be a high transfusion procedure. Frozen plasma (FP) is widely used despite mixed efficacy and safety data. Several centres perform LT with no or low volume of FP by using prothrombin complex concentrate (PCC). This systematic review and meta-analysis characterises the existing efficacy and safety data of PCC use in LT.

Methods: This review was registered (PROSPERO CRD#42024561866). MEDLINE, Embase, Cochrane, and ClinicalTrials.gov were searched from inception to 30 May 2024. Studies in adults undergoing LT where PCC exposure was reported in relation to clinical outcomes were included. Random effects models were used to obtain pooled effect estimates.

Results: All studies were retrospective, with seven reporting the number of patients receiving PCC [392/1901 (21%)], and one grouping patients receiving different factor concentrates together [576/939 (61%)]. Patients receiving PCC had worse preoperative coagulopathy, model for end-stage liver disease scores, and comorbidities. Patients exposed to PCC had a comparable mean number of red blood cell (RBC), plasma, or platelet units transfused. Use of viscoelastic testing-based algorithms incorporating PCC compared with usual care was associated with reduced odds of RBC exposure (odds ratio [OR]: 0.53, 95% confidence interval [CI]: 0.32-0.86, I²=0%) and FP exposure (OR: 0.35, 95% CI: 0.13-0.92, I²=50%), but not platelets. Safety outcomes were driven by one large study using PCC as rescue therapy.

Conclusions: Although there are no randomised trials comparing use of PCC vs FP in LT, their efficacy and safety appear comparable. Higher-quality studies are needed to assess PCC use for coagulopathic bleeding in LT.

Keywords: blood coagulation disorders; blood transfusion; end-stage liver disease; liver transplantation; prothrombin complex concentrates.

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Conflict of interest statement

Declarations of interest JB was supported in part by a merit award from the Department of Anaesthesiology and Pain Medicine, University of Toronto; has received research funding or honoraria from Octapharma, Grifols, and Canadian Blood Services. KG works as the Medical Director of Tem Innovations, Munich, Germany, and received lecture fees from Octapharma, Lachen, Switzerland. KK was supported in part by a merit award from the Department of Anesthesiology and Pain Medicine, University of Toronto; has received research support, honoraria, or consultancy for speaking. JC has received research support from CSL Behring, Octapharma, and Canadian Blood Services. SM has received honoraria from Octapharma and Instrumentation Laboratory. All co-authors contributed to the critique, selection, and interpretation of included studies. All studies were reviewed by at least two individuals without disclosures or financial conflicts of interest (NA, IK). The other authors declare no conflict of interest.

Figures

**Fig 1**
PRISMA flow diagram. PCC, prothrombin complex concentrate.

**Fig 2**
Forest plots for transfusion outcomes and adverse events.^,, , ^,^, CI, confidence interval; OR, odds ratio; PCC, prothrombin complex concentrate.

See this image and copyright information in PMC

References

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Use of prothrombin complex concentrates in liver transplantation: a systematic review and meta-analysis

Affiliations

Use of prothrombin complex concentrates in liver transplantation: a systematic review and meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

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Medical