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.

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 fibrinogen restoration during postpartum haemorrhage. Dedicated pharmacokinetic-pharmacodynamic studies are needed to optimise fibrinogen supplementation and hemostatic strategies.