PCC Outperforms Frozen Plasma in Cardiac Surgery Bleeding Control

Use of 4-factor prothrombin complex concentrate (PCC) was safe and efficacious relative to frozen plasma for the treatment of coagulopathic bleeding in cardiac surgery, according to new data.

Presented at the American College of Cardiology (ACC) 2025 Annual Scientific Sessions, results of the FARES-II trial provide insight into the potential of PCC to mitigate bleeding risk and reduce need for frozen plasma in patients who experience excessive bleeding in cardiac surgery.1

“Patients randomly assigned to treatment with 4F-PCC needed significantly fewer interventions to stop their bleeding, lost less blood, received fewer blood transfusions and had fewer surgical complications than those who were randomly assigned to be treated with frozen plasma,” said prinicipal investigator Keyvan Karkouti, MD, professor of anesthesiology in the department of anesthesiology and pain medicine at the University of Toronto.2 “The results suggest that using 4F-PCC to manage excessive bleeding during cardiac surgery potentially has substantial benefits for patients and the health care system by relieving pressure on the blood supply and other hospital resources.”

An unblinded, randomized, noninferiority trial, FARES-II enrolled adult patients who had undergone cardiac surgery requiring coagulation factor replacement due to excessive bleeding after cardiopulmonary bypass surgery. Conducted at 12 sites in the US and Canada, the trial enrolled a total of 528 patients, with 265 randomized to receive PCC and 263 randomized to receive frozen plasma in the operating room. Per trial protocol, a second dose was allowed over the next 24 hours if indicated, but thereafter only frozen plasma could be used.1

The primary outcome of interest for the study was hemostatic response, which was defined as effective if no hemostatic interventions occurred from 60 minutes to 24 hours after treatment initiation. Secondary outcomes of interest included allogeneic blood transfusions and adverse events. Investigators assessed the noninferiority of PCC relative to frozen plasma using a 10% margin and a 1-sided α of .025, with subsequent testing for superiority if noninferiority was demonstrated.1

Among the 538 patients enrolled in the trial, 420 were included in the primary analysis. This cohort had a median age of 66 (IQR, 57 to 73) years, 74% were male patients, 65% were White, and 296 underwent complex surgeries.1

Results of the study suggested the PCC group had a greater rate of hemostatic effectiveness (166 [77.9%] vs 125 [60.4%]; difference, 17.6%; 95% CI, 8.7% to 26.4%; P < .001 for noninferiority and superiority) and received fewer transfusions including red blood cells, platelets, and noninvestigational frozen plasma units than their counterparts in the frozen plasma group (mean, 6.6 units; 95% CI, 5.7-7.7 vs 9.3 units; 95% CI, 8.0-10.8; difference, 2.7; 95% CI, 1.0 to 4.4; P=.002).1

Safety analyses suggested 36.2% of the PCC group and 47.3% of the frozen plasma group experienced serious adverse events (Relative Risk [RR], 0.76; 95% CI, 0.61 to 0.96; P=.02). Additional safety data indicated 10.3% in the PCC group and 18.8% in the frozen plasma group experienced acute kidney injury (RR, 0.55; 95% CI, 0.34 to 0.89; P = .02).1

“Using 4F-PCC instead of frozen plasma could significantly reduce the need for frozen plasma in cardiac surgery,” Karkouti said.2 “This would free up the supply for other therapies.”

In an editorial comment simultaneously published in JAMA, Ryan Wang, MD, of Icahn School of Medicine at Mount Sinai, and Elliott Bennett-Guerrero, MD, of the Renaissance School of Medicine at Stony Brook University, opined on the trial’s findings and how it could impact care decisions in the future.3

“Is it time to replace plasma with prothrombin complex concentrate in cardiac surgery? The FARES-II trial provides substantial evidence that PCC, when used with a structured algorithm and point-of-care INR testing, is more effective than thawed frozen plasma at treating bleeding after cardiac surgery due to factor deficiency,” wrote the pair.3 “Administration of PCC may be beneficial in coagulopathic patients who cannot receive a large volume of thawed frozen plasma or for whom rapid reversal is important. However, the differences in blood products administered were modest in the FARES-II trial, and no differences were observed in mortality or in ICU or hospital length-of-stay, which may argue against a major clinical benefit for most patients.”

References:

1. 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. Published online March 29, 2025. doi:10.1001/jama.2025.3501

2. American College of Cardiology. Prothrombin Concentrate Superior to Frozen Plasma in Controlling Bleeding During Heart Surgery - American College of Cardiology. American College of Cardiology. Published March 29, 2025. Accessed March 29, 2025. https://www.acc.org/About-ACC/Press-Releases/2025/03/29/15/27/Prothrombin-Concentrate-Superior.

3. Wang R, Bennett-Guerrero E. Is It Time to Replace Plasma With Prothrombin Complex Concentrate in Cardiac Surgery? JAMA. Published online March 29, 2025. doi:10.1001/jama.2025.3644