title: Fibrinogen concentrate does not suppress endogenous fibrinogen synthesis in a 24-hour porcine trauma model.
abstract: BACKGROUND
  Fibrinogen concentrate may reduce blood loss after trauma. However, its effect on endogenous fibrinogen synthesis is unknown. The authors investigated the effect of exogenous human fibrinogen on endogenous fibrinogen metabolism in a 24-h porcine trauma model.
  
  
  METHODS
  Coagulopathy was induced in 20 German Landrace pigs by hemodilution and blunt liver injury. Animals were randomized to receive fibrinogen concentrate (100 mg/kg; infusion beginning 20 min postinjury and lasting approximately 10 min) or saline. Fibrinogen concentration, thromboelastometry, and quantitative reverse transcriptase polymerase chain reaction of fibrinogen genes in liver tissue samples were recorded. Internal organs were examined histologically for emboli.
  
  
  RESULTS
  Coagulation parameters were impaired and plasma fibrinogen concentrations were reduced before starting infusion of fibrinogen concentrate/saline. Twenty minutes after starting infusion, exogenous fibrinogen supplementation had increased plasma fibrinogen concentration versus controls (171 ± 19 vs. 63 ± 10 mg/dl [mean ± SD for Multifibren U]; 185 ± 30 vs. 41 ± 4 mg/dl [Thrombin reagent]; P < 0.05 for both comparisons). The between-group difference in plasma fibrinogen concentration diminished thereafter, with maximum concentrations in both groups observed at approximately 24 h, that is, during the acute-phase reaction after trauma. Fibrinogen supplementation did not down-regulate endogenous fibrinogen synthesis (no between-group differences in fibrinogen messenger RNA). Total postinjury blood loss was significantly lower in the fibrinogen group (1,062 ± 216 vs. 1,643 ± 244 ml; P < 0.001). No signs of thromboembolism were observed.
  
  
  CONCLUSIONS
  Administration of human fibrinogen concentrate did not down-regulate endogenous porcine fibrinogen synthesis. The effect on plasma fibrinogen concentration was most pronounced at 20 min but nonsignificant at approximately 24 h.
authors.affiliation: From the Department of Anesthesiology (C.Z., J.S., R.R., O.G.), Institute for Laboratory Animal Science (C.Z.), and Department of Pathology (T.B., M.R.), RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Zentai
authors.forename: Till
authors.initials: T
authors.lastname: Braunschweig
authors.forename: Jonas
authors.initials: J
authors.lastname: Schnabel
authors.forename: Michael
authors.initials: M
authors.lastname: Rose
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Oliver
authors.initials: O
authors.lastname: Grottke
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism*; D008297:Male; D011897:Random Allocation; D013552:Swine; D013997:Time Factors; D014949:Wounds, Nonpenetrating / Q000378:metabolism*
chemical_list: D005340:Fibrinogen