Effects of Fibrinogen Concentrate on Thrombin Generation, Thromboelastometry Parameters, and Laboratory Coagulation Testing in a 24-Hour Porcine Trauma Model

Clin Appl Thromb Hemost. 2016 Nov;22(8):749-759. doi: 10.1177/1076029615584662. Epub 2015 May 6.

Abstract

Introduction: In a 24-hour porcine model of liver injury, we showed that fibrinogen supplementation does not downregulate endogenous fibrinogen synthesis. Here we report data from the same study showing the impact of fibrinogen on coagulation variables.

Materials and methods: Coagulopathy was induced in 20 German land race pigs by hemodilution and blunt liver injury. Animals randomly received fibrinogen concentrate (100 mg/kg) or saline. Coagulation parameters were assessed and thromboelastometry (ROTEM) was performed.

Results: Fibrinogen concentrate significantly reduced the prolongations of EXTEM clotting time, EXTEM clot formation time, and prothrombin time induced by hemodilution and liver injury. A decrease in clot strength was also ameliorated. Endogenous thrombin potential was significantly higher in the fibrinogen group than in the control group, 20 minutes (353 ± 24 vs 289 ± 22 nmol/L·min; P < .05) and 100 minutes (315 ± 40 vs 263 ± 38 nmol/L·min; P < .05) after the start of infusion. However, no significant between-group differences were seen in other thrombin generation parameters or in d-dimer or thrombin-antithrombin levels. Fibrinogen-platelet binding was reduced following liver injury, with no significant differences between groups. No significant between-group differences were observed in any parameter at ∼12 and ∼24 hours.

Conclusion: This study suggests that, in trauma, fibrinogen supplementation may shorten some measurements of the speed of coagulation initiation and produce a short-lived increase in endogenous thrombin potential, potentially through increased clotting substrate availability. Approximately 12 and 24 hours after starting fibrinogen concentrate/saline infusion, all parameters measured in this study were comparable in the 2 study groups.

Keywords: bleeding; blood coagulation factors; hemostasis.

MeSH terms

  • Animals
  • Blood Coagulation Tests / methods*
  • Disease Models, Animal
  • Down-Regulation
  • Fibrinogen / biosynthesis
  • Fibrinogen / metabolism
  • Fibrinogen / pharmacology*
  • Hemodilution
  • Hemostasis
  • Humans
  • Liver / injuries
  • Male
  • Random Allocation
  • Swine
  • Thrombelastography / methods*
  • Thrombin / metabolism*
  • Wounds, Nonpenetrating / blood*

Substances

  • Fibrinogen
  • Thrombin