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

ObjectivesTo analyse which fibrinogen source may improve coagulation using an in vitro 33% dilutional coagulopathy model. BackgroundUncritical 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 MethodsBy 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. ResultsThe dilution was associated with decreased haemoglobin and haematocrit levels. Fibrinogen supplementation with fibrinogen-containing formulations led to increased fibrinogen levels (FFP: 1722 174 mg dL(-1); Fib(low): 2115 +/- 2061 mg dL(-1); Fib(high): 2558 +/- 214 mg dL(-1)) than in a diluted-only sample (1555 +/- 197 mg dL(-1)). Extrinsically activated assay with tissue factor (EXTEM) clot formation times, -angles and maximum clot firmness significantly improved in the groups of Fib(low) + FXIII (79 +/- 122 s; 743 +/- 24 degrees; 62 +/- 23 mm), Fib(high) (708 +/- 106 s; 762 +/- 27 degrees; 643 +/- 23 mm) and Fib(high) + FXIII (698 +/- 115 s; 775 +/- 27 degrees; 6433 +/- 25 mm) compared with the dilution groups (1042 +/- 19 s; 697 +/- 29 degrees; 565 +/- 31 mm). In contrast, rotational thromboelastometric trace (ROTEM) measures of samples supplemented with FFP largely remained unchanged. ConclusionFibrinogen 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.