Patients who receive 4-factor prothrombin complex concentrate (PCC) for bleeding complications during cardiac surgery have superior hemostatic and safety outcomes compared with patients who receive frozen plasma, a new analysis shows. These data were reported by Keyvan Karkouti, MD, of the University of Toronto, and colleagues, in a manuscript published online in the Journal of the American Medical Association. Bleeding is a common complication that increases morbidity and mortality in patients undergoing cardiac surgery, with up to 15% of patients experiencing excessive bleeding. Frozen plasma is the most utilized therapy for bleeding related to coagulation factor deficiencies, but some trials show that PCC might be an alternate management strategy. “Point of care testing and algorithmic transfusion protocols in addition to PCC may also contribute to the better treatment of bleeding after cardiac surgery,” Thomas MacGillivray, MD, Physician Executive Director and Chairman of Cardiac Surgery at MedStar Washington Hospital Center, Washington, DC, told CRTonline. The investigators in this unblinded, randomized, noninferiority trial, FARES-II (Factor Replacement in Surgery II), examined the safety and efficacy of PCC versus frozen plasma in this patient population. Adults who underwent surgery and experienced bleeding related to coagulation factor deficiencies post-termination of cardiopulmonary bypass were included. The primary outcome of this study was hemostatic response if no hemostatic interventions took place from 60 minutes through 24 hours post-treatment. Adverse events and allogeneic blood transfusions were analyzed as secondary outcomes. A total of 265 patients from 12 hospitals in Canada and the U.S. were randomized to receive PCC, and 263 were randomized to receive frozen plasma. If needed, a second dose was provided within 24 hours, in which only frozen plasma could be used. Patients were followed for 30 days. A total of 420 patients (plasma n=207, PCC n=213) were included in the final analysis (median age=66 years, 74% male; 65% white, 10% Asian, 1% Black), and 70% of this patient group underwent complex surgeries. Patients in the PCC group had higher overall hemostatic effectiveness compared with the plasma group (77.9% versus 60.4%; 95% confidence interval [CI]=8.7-26.4, p<0.001 for noninferiority and superiority). Fewer transfusions — red blood cells, platelets and noninvestigational frozen plasma units — were performed in the PCC group (mean=6.6 units, 95% CI=5.7-7.7) versus the plasma group (mean=9.3 units, 95% CI=8.0-10.8) (difference=17.6%, 95% CI=0.61-0.96, p=0.02). Acute kidney injury was observed in 10.3% of patients in the PCC group and 18.8% of patients in the plasma group (95% CI=0.34-0.89, p=0.02). Overall, patients who received PCC had better hemostatic efficiency and safety outcomes compared with patients who received frozen plasma in those who underwent cardiac surgery and required coagulation factor replacement for bleeding complications. In an accompanying editorial, Ryan Wang, MD, of the Icahn School of Medicine at Mount Sinai, New York, and Elliott Bennett-Guerrero, MD, of the Renaissance School of Medicine at Stony Brook University, New York, discussed the replacement of plasma with PCC to treat bleeding during cardiac surgery. The editorialists wrote that institutional constraints may prevent clinicians from using PCC, particularly the high costs of PCC compared with plasma. But this could be examined in future research, especially if fewer follow-up treatments are needed in patients who receive PCC. “This study’s findings make a compelling case for the benefits of prothrombin complex concentrates (PCC) over fresh frozen plasma (FFP) to treat bleeding due to coagulation factor deficiency after cardiac surgery,” said Dr. MacGillivray. “PCC appears to be faster, more effective and safer to control coagulopathic bleeding after heart surgery. Perhaps the cost savings of less time spent in the operating room will than offset the higher expense of PCC compared with FFP.” Sources: Karkouti K, Callum JL, Bartoszko J, et al. Prothrombin complex concentrate vs frozen plasma for coagulopathic bleeding in cardiac surgery: The FARES-II multicenter randomized clinical trial. JAMA. 2025 April 16 (Article in press). Wang R, Bennett-Guerrero E. Is it time to replace plasma with prothrombin complex concentrate in cardiac surgery? JAMA. 2025 April 16 (Article in press). Image Credit: Paul– stock.adobe.com