In vitro effects of different sources of fibrinogen supplementation on clot initiation and stability in a model of dilutional coagulopathy

Abstract

Objectives: To analyse which fibrinogen source may improve coagulation using an in vitro 33% dilutional coagulopathy model.

Background: Uncritical volume resuscitation in the context of trauma haemorrhage contributes to the iatrogenic arm of the acute trauma-induced coagulopathy through dilution and depletion of coagulation factors, with fibrinogen reaching critical levels first.

Materials and methods: By using an experimental model of 33% dilutional coagulopathy, we have analysed which fibrinogen source may exert superior effects on improving haemocoagulative capacities and correcting depleted fibrinogen levels. As fibrinogen sources, we supplemented (i) fresh frozen plasma (FFP), (ii) fibrinogen concentrate low-dose (Fib_low ) and (iii) fibrinogen concentrate high-dose (Fib_high ), the latter both in the presence and absence of additional FXIII.

Results: The dilution was associated with decreased haemoglobin and haematocrit levels. Fibrinogen supplementation with fibrinogen-containing formulations led to increased fibrinogen levels (FFP: 172·2 ± 17·4 mg dL^-1 ; Fib_low : 211·5 ± 20·61 mg dL^-1 ; Fib_high : 255·8 ± 21·4 mg dL^-1 ) than in a diluted-only sample (155·5 ± 19·7 mg dL^-1 ). Extrinsically activated assay with tissue factor (EXTEM) clot formation times, α-angles and maximum clot firmness significantly improved in the groups of Fib_low + FXIII (79 ± 12·2 s; 74·3 ± 2·4°; 62 ± 2·3 mm), Fib_high (70·8 ± 10·6 s; 76·2 ± 2·7°; 64·3 ± 2·3 mm) and Fib_high + FXIII (69·8 ± 11·5 s; 77·5 ± 2·7°; 64·33 ± 2·5 mm) compared with the dilution groups (104·2 ± 19 s; 69·7 ± 2·9°; 56·5 ± 3·1 mm). In contrast, rotational thromboelastometric trace (ROTEM) measures of samples supplemented with FFP largely remained unchanged.

Conclusion: Fibrinogen concentrates corrected and improved haemodilution-induced changes in blood clotting in vitro. High-dose fibrinogen supplementation was associated with correction and improvement in clot dynamics and stability.

Keywords: coagulopathy; factor XIII; fibrinogen; fresh frozen plasma; haemocoagulative capacity; haemorrhage; haemostatic potential; trauma-induced coagulopathy.