Potentially practice-changing formulation for cardiac surgery-related bleeding?

A 4-factor prothrombin complex concentrate (PCC) demonstrated superiority over frozen plasma (FP) among cardiac surgery patients with coagulopathy who displayed bleeding. Haemostatic responses were improved in the PCC arm, and PCC may have safety advantages over FP.

Dr Keyvan Karkouti (University of Toronto, Canada) presented the results of the phase 3 FARES-II (LEX-211) trial (NCT05523297), in which adult cardiac surgery patients with coagulopathy who had bleeding or were anticipated to bleed were randomised 1:1 to the standard-of-care of FP or to PCC [1]. PCC is a purified, concentrated, and pathogen-reduced derivative of plasma that contains a subset of pro-coagulant factors but does not require thawing or ABO blood type matching. In total, 213 trial participants were treated with PCC and 207 were treated with FP. The primary endpoint was ‘effective haemostatic treatment response’, defined as not needing additional haemostatic interventions from 60 minutes to 24 hours after administration of the first dose.

An effective haemostatic treatment response was reported for 77.9% of the participants in the PCC arm and for 60.4% of those in the FP arm, a significant difference (Δ17.55; 95% CI 8.70–26.40; P<0.001). The corresponding relative risk of haemostatic failure was RR 0.56 (95% CI 0.41–0.75), in favour of the PCC arm. Furthermore, the safety profile of PCC appeared to be more acceptable than that of FP; the rate of serious adverse events was lower in the PCC arm than in the FP arm (36.2% vs 47.3%; RR 0.76; 95% CI 0.61–0.96; P=0.02). For example, acute kidney injury was less common in the PCC arm (10.3% vs 18.8%; RR 0.55; 95% CI 0.34–0.89; P=0.02; see Table).

Table: Safety within 30 days after surgery [1]



AE, adverse events; FP, frozen plasma; ICU, intensive care unit; IQR, interquartile range; PCC, prothrombin complex concentrate.

“PCC proved superior to FP for haemostatic response in the management of excessive bleeding related to coagulation factor deficiency in patients undergoing cardiac surgery,” concluded Dr Karkouti. “Together with the observed safety advantages of PCC over FP, this may be a practice-changing study for bleeding management in cardiac surgery.”

1. Karkouti K, et al. Four-factor prothrombin complex concentrate is superior to frozen plasma in bleeding adult cardiac surgery patients with coagulopathy: results from a phase 3 randomized, active-control study. Late-breaking Clinical Trials II, ACC 2025 Scientific Session, 29–31 March, Chicago, USA.

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Posted on 22 May 202522 May 2025