Fibrinogen concentrate does not suppress endogenous fibrinogen synthesis in a 24-hour porcine trauma model.

Fibrinogen concentrate is increasingly used for the management of major bleeding in a variety of clinical settings. One of the safety issues is the extent to which exogenous fibrinogen could affect the normal acute-phase reaction. Although studies that compared fibrinogen concentrate with other standard therapies did not report any difference in plasma fibrinogen levels at 24 hours, the underlying mechanisms are not understood. In this study, Zentai et al. hypothesized that the lack of difference between patients treated with fibrinogen concentrate and those treated with allogeneic blood products could be explained by one or more of the following reasons: (i) downregulation of endogenous fibrinogen synthesis, (ii) increased consumption or metabolism of fibrinogen in circulation, or (iii) a shift to the extravascular space.

The authors used a porcine trauma model in which coagulopathy was induced by haemodilution and blunt liver injury. The animals were randomised to receive either fibrinogen concentrate (100 mg/kg) or normal saline. Rotational thromboelastometry and quantitative reverse transcriptase polymerase chain reaction were used to assess the relationship between fibrinogen infusion and both endogenous and exogenous fibrinogen kinetics. The authors report that administration of fibrinogen concentrates increased plasma concentrations of total fibrinogen but had no impact on concentrations of endogenous porcine fibrinogen. The difference between both groups was maximal 20 minutes after infusion but the difference became nonsignificant within the first 24 hours. Finally, total blood loss after injury was significantly decreased in the treatment group compared with the control group.

In this animal study, the authors report that the absence of difference in fibrinogen levels between animals treated with fibrinogen concentrates and controls could not be explained by a downregulation of endogenous fibrinogen synthesis. Further studies are needed to better assess whether this pharmacokinetic observation could be explained by an increased consumption or metabolism of fibrinogen in circulation.

– David Faraoni

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