title: Recombinant factor VIIa and fibrinogen display additive effect during in vitro haemodilution with crystalloids.
abstract: BACKGROUND
  Major blood loss requires fluid resuscitation for maintaining hemodynamic stability. Excessive volume infusions predispose to dilutional coagulopathy through loss, consumption and dilution of cells and proteins involved in haemostasis. Further treatment with fibrinogen concentrate and/or recombinant activated factor VII (rFVIIa) may be initiated, although the haemostatic effects in a situation with haemodilution are not fully detailed. The present study evaluates haemostatic effect of fibrinogen and rFVIIa and their combination in an in vitro model of haemodiluted whole blood with two commonly used crystalloids.
  
  
  METHODS
  Eight healthy, male volunteers were enrolled. Outcome variables were clot initiation, propagation and strength assessed by thrombelastographic parameters: clotting time, clot formation time, maximum velocity, time until maximum velocity, maximum clot firmness evaluated at dilution levels of 0% (control), 10%, 30% and 50% with isotonic saline and Ringer's lactate in a model of tissue factor-activated whole blood. Fibrinogen and rFVIIa were additional final reaction concentrations, reflecting commonly used clinically therapeutic dosages.
  
  
  RESULTS
  Dose-dependent coagulopathy developed following haemodilution with isotonic saline and Ringer's lactate, characterised by a prolonged clot initiation, reduced clot propagation and reduced clot strength. Fibrinogen improved clot strength and propagation phase while rFVIIa shortened clot initiation, both with a positive dose dependency.
  
  
  CONCLUSIONS
  The combination of fibrinogen and rFVIIa displays an additive effect and improves overall in vitro whole blood clot formation in a model of in vitro crystalloid-induced haemodilution.
authors.affiliation: Department of Anesthesiology, Center for Haemophilia and Thrombosis, Aarhus University Hospital, Aarhus, Denmark. chfen@dadlnet.dk
authors.forename: C
authors.initials: C
authors.lastname: Fenger-Eriksen
authors.forename: E
authors.initials: E
authors.lastname: Tønnesen
authors.forename: J
authors.initials: J
authors.lastname: Ingerslev
authors.forename: B
authors.initials: B
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D000077324:Crystalloid Solutions; D015942:Factor VIIa / Q000494:pharmacology*; D005340:Fibrinogen / Q000494:pharmacology*; D006438:Hemodilution; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D007552:Isotonic Solutions; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D017186:Titrimetry
chemical_list: D000077324:Crystalloid Solutions; D006490:Hemostatics; D007552:Isotonic Solutions; D011994:Recombinant Proteins; D005340:Fibrinogen; C103587:recombinant FVIIa; D015942:Factor VIIa