title: High-dose fibrinogen versus a clinically recommended dose of fresh frozen plasma for reversal of dilutional coagulopathy in an in vitro model of severe hemodilution.
abstract: BACKGROUND
  Volume substitution using colloids and crystalloids dose-dependently induces dilutional coagulopathy. For treatment, fibrinogen concentrate and fresh frozen plasma are options, though the effective dosage of either agent is unclear. The objective of this study was to evaluate, whether high-dose fibrinogen or recommended doses of fresh frozen plasma are equally effective in reversing profound dilutional coagulopathy in vitro.
  
  
  METHODS
  Blood samples of ten healthy volunteers were diluted by 60% with normal saline, balanced 4% gelatin, or balanced 6% hydroxyethyl starch 130/0.42, and supplemented with either 85mg/kg fibrinogen concentrate or 20mL/kg fresh frozen plasma. Conventional coagulation assays (prothrombin time, activated partial thromboplastin time, plasma fibrinogen, factors V and VIII), and activated rotational thromboelastometry (EXTEM: clotting time, clot formation time,
  maximum clot firmness) were performed in all samples.
  
  
  RESULTS
  For saline and gelatin dilutions, plasma fibrinogen and thromboelastometry parameters normalized by fibrinogen concentrate, while conventional coagulation assays and factors V and VIII remained unaffectedly impaired. Fresh frozen plasma improved both conventional coagulation assays, coagulation factors, and thromboelastometry parameters in saline and gelatin dilutions. For hydroxyethyl starch dilutions, plasma fibrinogen increased by fresh frozen plasma, and even normalized by fibrinogen concentrate. Conventional coagulation assays and factors V and VIII improved by fresh frozen plasma only. Thromboelastometry parameters remained mainly unaffected impaired by both fibrinogen concentrate and fresh frozen plasma.
  
  
  CONCLUSIONS
  High-dose fibrinogen concentrate and clinically recommended doses of fresh frozen plasma are equally effective and can partially restore viscoelastic coagulation assays in profound saline and gelatin dilutions, but only fresh frozen plasma improves conventional coagulation assays. Hydroxyethyl starch-induced disturbance of fibrin polymerization is neither restored by fibrinogen concentrate nor fresh frozen plasma.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-University Medicine Berlin, Berlin, Germany - christoph.rosenthal@charite.de.
authors.forename: C
authors.initials: C
authors.lastname: Rosenthal
authors.forename: J
authors.initials: J
authors.lastname: Rau
authors.forename: T
authors.initials: T
authors.lastname: Volk
authors.forename: M
authors.initials: M
authors.lastname: Sander
authors.forename: S
authors.initials: S
authors.lastname: Ziemer
authors.forename: C
authors.initials: C
authors.lastname: Von Heymann
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000209:etiology*; D001780:Blood Coagulation Tests; D005340:Fibrinogen / Q000627:therapeutic use*; D006438:Hemodilution / Q000009:adverse effects*; D006801:Humans; D010949:Plasma
chemical_list: D005340:Fibrinogen