Prothrombin complex concentrate versus plasma for coagulopathic bleeding after cardiac surgery with cardiopulmonary bypass: a systematic review and meta-analysis

Abstract

Introduction: Coagulopathic bleeding after cardiac surgery with cardiopulmonary bypass is a frequent complication associated with increased transfusion requirements, surgical re-exploration, organ injury, and mortality. Fresh frozen plasma has traditionally been the cornerstone of treatment; however, its use requires large-volume administration and results in variable hemostatic response. Prothrombin complex concentrate (PCC) has emerged as a potentially effective alternative, although concerns remain regarding its clinical effectiveness and safety. Objective: To evaluate the effectiveness and safety of three- or four-factor PCC compared with plasma-based standard care strategies for managing clinically relevant coagulopathic bleeding after cardiac surgery with cardiopulmonary bypass. Methods: A systematic review and meta-analysis of randomized controlled trials and comparative observational studies was conducted. Searches were performed in PubMed, Embase, and LILACS, from inception to February 11, 2026; manual screening of reference lists of included studies and relevant reviews was also performed. No gray literature, trial registries, or conference proceedings were searched. The primary outcome was clinically relevant hemostatic failure. Secondary outcomes included acute kidney injury, thromboembolic events, and mortality. Randomized trials were considered primary evidence, while observational studies were synthesized exploratorily. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence using GRADE. Results: Five studies (two randomized controlled trials and three observational studies) were included. In randomized trials, PCC reduced clinically relevant hemostatic failure (RR 0.55; 95% CI 0.42-0.70; p < 0.001; I² = 0%) as well as acute kidney injury (RR 0.57; 95% CI 0.35-0.91; p = 0.017; I² = 0%) when compared with plasma. No statistically significant differences were observed for thromboembolic events (RR 1.22; 95% CI 0.57-2.60; p = 0.615; I² = 0%) or mortality (RR 0.66; 95% CI 0.21-2.03; p = 0.469; I² = 0%). Certainty of evidence was moderate for clinically relevant hemostatic failure and acute kidney injury, and low for thromboembolic events and mortality. The wide confidence intervals for thromboembolic events and mortality indicate that clinically important harm cannot be excluded. Conclusions: Among adults undergoing cardiac surgery with cardiopulmonary bypass who develop clinically relevant coagulopathic bleeding, PCC may improve hemostatic control and reduce acute kidney injury compared with plasma-based strategies. However, the evidence is limited by the small number of open-label randomized trials and by imprecision for thromboembolic events and mortality; therefore, safety conclusions should be considered provisional.