Excessive bleeding is a common complication of cardiac surgery that can increase the risk of mortality. In a recent clinical trial, researchers at the Toronto General Hospital Research Institute (TGHRI) found that a drug called prothrombin complex concentrate (PCC, which goes by the brand name Octaplex®/Balfaxar®) is more effective at treating this complication than current treatments.
One important contributor to excessive bleeding after cardiac surgery is the depletion of enzymes that help blood clot. The standard treatment for this complication is the transfusion of frozen plasma (FP)—the liquid part of blood that contains clotting factors and is frozen for later use.
However, data on FP's effectiveness is limited, and it can cause life-threatening complications such as serious allergic reactions, transfusion-related acute lung injury, and transfusion-associated circulatory overload.
Recent preliminary data suggests that PCC, which is derived from large plasma pools and contains blood clotting factors and other proteins, may be a safer alternative to FP. A recent pilot study by a research team, led by Dr. Keyvan Karkouti, Senior Scientist at TGHRI, found that PCC may be more effective than FP in treating bleeding without increasing risk.
To confirm these results and determine PCC’s safety and efficacy in a larger, randomized trial, Dr. Karkouti’s team studied 420 adult cardiac surgery patients who required clotting factor replacement due to excessive bleeding after their procedure. They found that PCC was better than FP at stopping bleeding (77.9% versus 60.4% effectiveness). Serious adverse events were also less common (36.2% versus 47.3%), as was acute kidney injury (10.3% versus 18.8%).
“These findings indicate that PCC is a potential new treatment for managing bleeding in cardiac surgery. PCC benefits both patients and the health care system by reducing bleeding and the need for transfusions,” says Dr. Karkouti, co-lead of the study. "However, the clinical and financial impacts of this change need to be assessed in future studies.”
Dr. Keyvan Karkouti, Senior Scientist at the Toronto General Hospital Research Institute (TGHRI) and Professor in the Department of Anesthesiology and Pain Medicine at the University of Toronto (U of T), is the corresponding and co-first author of the study.
Dr. Jeannie L. Callum, Professor in the Department of Pathology and Molecular Medicine at Queen’s University and Associate Scientist at Sunnybrook Health Sciences Centre, is a co-first author of the study.
Authorship for this study also includes the FARES-II study group.
This work was supported by Octapharma AG, the Canadian Institutes of Health Research, the Department of Anesthesiology and Pain Medicine at the University of Toronto, and UHN Foundation.
The trial was conducted jointly by Octapharma AG (the sponsor), the Department of Anesthesia and Pain Management Clinical Trials Unit (ACTU) at UHN, and Ozmosis Research Inc.
Karkouti K, Callum JL, Bartoszko J, Tanaka KA, Knaub S, Brar S, Ghadimi K, Rochon A, Mullane D, Couture EJ, Lin Y, Harle C, Zeller M, Tran DTT, Solomon C, Rao V, Law M, Butt AL, Chen EP, Martins MR, Saha T, Shih AW, Vézina MC, Moussa F, Pereira Cezar Zamper R, Syed S, Buyukdere H, Werner S, Grewal D, Wong D, Vandyck KB, Tanzola R, Hughes B, Royer O, Wong S, Levy JH; FARES-II Study Group. Prothrombin Complex Concentrate vs Frozen Plasma for Coagulopathic Bleeding in Cardiac Surgery: The FARES-II Multicenter Randomized Clinical Trial. JAMA. 2025 Mar 29. doi: 10.1001/jama.2025.3501.