title: Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes.
abstract: BACKGROUND
  Low fibrinogen levels are known to occur in trauma. However, the extent of fibrinogen depletion during trauma hemorrhage, the response to replacement therapy and association with patient outcomes remain unclear.
  
  
  OBJECTIVE
  The study aims were to: characterize admission fibrinogen level and correlate it with factors associated with injury; describe the time course of fibrinogen depletion and response to replacement therapy; determine the correlation of fibrinogen level with rotational thromboelastography (ROTEM) parameters; evaluate the effect of fibrinogen supplementation ex vivo; and establish the association between fibrinogen level and clinical outcomes.
  
  
  METHODS
  This was a prospective cohort study of 517 patients. Blood samples were drawn on admission and after admistration of every 4 units of packed red blood cells. Fibrinogen levels were determined with the Clauss method, and global hemostatic competence was assessed with thromboelastometry. The effect of fibrinogen supplementation was assessed in a subgroup of coagulopathic patients.
  
  
  RESULTS
  Low admission fibrinogen level was independently associated with injury severity score (P < 0.01), shock (P < 0.001), and prehospital fluid volume (P < 0.001). Fibrinogen supplementation during transfusion maintained but did not augment fibrinogen levels. Administration of cryoprecipitate was associated with improved survival. ROTEM parameters correlated with fibrinogen level, and ex vivo fibrinogen administration reversed coagulopathic ROTEM parameters. Fibrinogen level was an independent predictor of mortality at 24 h and 28 days (P < 0.001).
  
  
  CONCLUSIONS
  Fibrinogen level is decreased in injured patients on admission and is associated with poor outcomes. ROTEM is a rapid means of assessing hypofibrinogenemia. Earlier administration of specific fibrinogen replacement may improve outcomes, and prospective controlled trials are urgently needed.
authors.affiliation: Trauma Sciences, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Rourke
authors.forename: N
authors.initials: N
authors.lastname: Curry
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: R
authors.initials: R
authors.lastname: Taylor
authors.forename: I
authors.initials: I
authors.lastname: Raza
authors.forename: R
authors.initials: R
authors.lastname: Davenport
authors.forename: S
authors.initials: S
authors.lastname: Stanworth
authors.forename: K
authors.initials: K
authors.lastname: Brohi
mesh_terms: D000328:Adult; D017707:Erythrocyte Transfusion; D005260:Female; D005340:Fibrinogen / Q000378:metabolism* / Q000627:therapeutic use; D006470:Hemorrhage / Q000097:blood* / Q000188:drug therapy / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000097:blood* / Q000188:drug therapy / Q000628:therapy
chemical_list: D005340:Fibrinogen