Hyperfibrinolysis and reduced functional fibrinogen in haemorrhagic caesarean delivery: a secondary analysis of the TRACES trial evaluating fibrinogen kinetics following fibrinogen concentrate or plasma infusion

Authors: Hureau, M; Lanoiselée, J; Ollier, E; Abraham, E; Denys, B; Bouthors, A-S

Affiliations: Anesthesia and Intensive Care Department, Jeanne de Flandre Academic Women Hospital, Centre Hospitalier Universitaire, FR59 Lille, France; Lille University, GRITA Research Group, ULR 7365, FR59 Lille, France, CHU St Etienne, Dysfonction Vasculaire et Hémostase, INSERM, U1059, 42023 Saint‑Étienne, France.

Publication: International journal of obstetric anesthesia; 2026; 66. 104846

ABSTRACT: INTRODUCTION: Postpartum haemorrhage-induced coagulopathy is marked by early fibrinogen depletion and, in acute obstetric coagulopathy, by hyperfibrinolysis and fibrinogenolysis. It remains unclear that exogenous fibrinogen concentrate is similarly susceptible to plasmin-mediated degradation. This secondary analysis of the TRACES trial assessed fibrinogen restoration kinetics after fibrinogen concentrate administration during postpartum hemorrhage. METHODS: The TRACES trial was a multicentre, randomised, double-blind, placebo-controlled study investigating tranexamic acid dosing in haemorrhagic caesarean delivery. For this analysis, only patients receiving fibrinogen concentrate were included. All laboratory and clinical data were re-timestamped relative to the first fibrinogen concentrate administration. Hyperfibrinolysis (HF) was defined by fibrinogen < 300 mg/dL, D-dimer ≥ 50,000 ng/mL and plasmin-antiplasmin complexes ≥ 2,000 ng/mL at any time point. Fibrinogen restoration trajectories were compared between cases with HF and No HF. RESULTS: Among 151 patients, 34 received fibrinogen concentrate. Five met HF criteria. Despite receiving higher fibrinogen concentrate doses, HF patients showed significantly impaired fibrinogen restoration (p < 0.01), with an initial rise followed by early decline. HF status was also associated with increased blood loss during postpartum hemorrhage. DISCUSSION: These exploratory findings support the hypothesis that exogenous fibrinogen may undergo plasmin-mediated cleavage in acute obstetric coagulopathy, leading to restoration failure and highlight the hypothesis of fibrinogenolysis. CONCLUSION: Hyperfibrinolysis markedly impairs fibrinogen concentrate-mediated fibrinogenrestoration during postpartum haemorrhage. Dedicated pharmacokinetic-pharmacodynamic studies are needed to optimise fibrinogen supplementation and hemostatic strategies.