title: Clinical and mechanistic drivers of acute traumatic coagulopathy.
abstract: BACKGROUND
  Acute traumatic coagulopathy (ATC) occurs after severe injury and shock and is associated with increased bleeding, morbidity, and mortality. The effects of ATC and hemostatic resuscitation on outcome are not well-explored. The PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study provided a unique opportunity to characterize coagulation and the effects of resuscitation on ATC after severe trauma.
  
  
  METHODS
  Blood samples were collected upon arrival on a subset of PROMMTT patients. Plasma clotting factor levels were prospectively assayed for coagulation factors. These data were analyzed with comprehensive PROMMTT clinical data.
  
  
  RESULTS
  There were 1,198 patients with laboratory results, of whom 41.6% were coagulopathic. Using international normalized ratio of 1.3 or greater, 41.6% of patients (448) were coagulopathic, while 20.5% (214) were coagulopathic using partial thromboplastin time of 35 or greater. Coagulopathy was primarily associated with a combination of an Injury Severity Score (ISS) of greater than 15 and a base deficit (BD) of less than -6 (p < 0.05). Regression modeling for international normalized ratio-based coagulopathy shows that prehospital crystalloid (odds ratio [OR], 1.05), ISS (OR, 1.03), Glasgow Coma Scale (GCS) score (OR, 0.93), heart rate (OR, 1.08), systolic blood pressure (OR, 0.96), BD (OR, 0.92), and temperature (OR, 0.84) were significant predictors of coagulopathy (all p < 0.03). A subset of 165 patients had blood samples collected and coagulation factor analysis performed. Elevated ISS and BD were associated with elevation of aPC and depletion of factors (all p < 0.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p < 0.04). Similar results were found for partial thromboplastin time-defined coagulopathy.
  
  
  CONCLUSIONS
  ATC is associated with the depletion of factors I, II, V, VII, VIII, IX, and X and is driven by the activation of the protein C system. These data provide additional mechanistic understanding of the drivers of coagulation abnormalities after injury. Further understanding of the drivers of ATC and the effects of resuscitation can guide factor-guided resuscitation and correction of coagulopathy after injury.
authors.affiliation: Division of General Surgery, Department of Surgery, School of Medicine, University of California San Francisco, San Francisco, California, USA. mcohen@sfghsurg.ucsf.edu
authors.forename: Mitchell Jay
authors.initials: MJ
authors.lastname: Cohen
authors.forename: Matt
authors.initials: M
authors.lastname: Kutcher
authors.forename: Britt
authors.initials: B
authors.lastname: Redick
authors.forename: Mary
authors.initials: M
authors.lastname: Nelson
authors.forename: Mariah
authors.initials: M
authors.lastname: Call
authors.forename: M Margaret
authors.initials: MM
authors.lastname: Knudson
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schreiber
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Bulger
authors.forename: Peter
authors.initials: P
authors.lastname: Muskat
authors.forename: Louis H
authors.initials: LH
authors.lastname: Alarcon
authors.forename: John G
authors.initials: JG
authors.lastname: Myers
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Rahbar
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Brasel
authors.forename: Herb A
authors.initials: HA
authors.lastname: Phelan
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: del Junco
authors.forename: Erin E
authors.initials: EE
authors.lastname: Fox
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wade
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Cotton
authors.forename: Nena
authors.initials: N
authors.lastname: Matijevic
mesh_terms: D000328:Adult; D001778:Blood Coagulation Disorders / Q000209:etiology* / Q000401:mortality; D001803:Blood Transfusion / Q000379:methods*; D005260:Female; D005440:Fluid Therapy / Q000009:adverse effects / Q000379:methods; D006470:Hemorrhage / Q000401:mortality / Q000628:therapy*; D017052:Hospital Mortality; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012044:Regression Analysis; D012151:Resuscitation / Q000379:methods; D018709:Statistics, Nonparametric; D015996:Survival Rate; D065227:Transfusion Reaction; D014193:Trauma Centers; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014947:Wounds and Injuries / Q000401:mortality / Q000628:therapy*