title: Evolving beyond the vicious triad: Differential mediation of traumatic coagulopathy by injury, shock, and resuscitation.
abstract: BACKGROUND
  A subset of trauma patients with critical injury present with coagulopathy, portending markedly worse outcomes. Clinical practice is evolving to treat the classical risk factors of hypothermia, hemodilution, and acidosis; however, coagulopathy persists even in the absence of these factors. We sought to determine the relative importance of injury- and shock-specific factors compared with resuscitation-associated factors in coagulopathy after trauma.
  
  
  METHODS
  Comprehensive demographic data, laboratory data, and outcomes data were prospectively collected from seven trauma centers over 8 years (November 2003 to August 2011) as part of the Inflammation and the Host Response to Injury Large-Scale Collaborative Program. A total of 1,537 critically injured patients with blunt trauma and hemorrhagic shock were analyzed to evaluate predictors of admission coagulopathy (international normalized ratio [INR] ≥ 1.3), multiorgan failure, and mortality.
  
  
  RESULTS
  Of 1,537 patients, 578 (37.6%) had admission INR of 1.3 or greater. Coagulopathic patients had more severe injury, more severe base deficit and lactate levels, as well as lower admission temperature, lower pH, and higher prehospital crystalloid volume (all p < 0.001). Coagulopathic patients required more blood products and mechanical ventilation and had higher rates of nosocomial infection, multiorgan failure, and mortality (all p < 0.02). Injury severity, temperature, and acidosis (all p < 0.02) independently predicted coagulopathy in multivariate analysis, with a significant interaction between lactate and prehospital crystalloid. In Cox regression models, however, coagulopathy itself remained an independent predictor of both multiorgan failure and mortality (p < 0.02) even when adjusted for injury severity, shock, and elements of the vicious triad.
  
  
  CONCLUSIONS
  Most patients with coagulopathy after trauma have mixed risk factors; however, coagulopathy has deleterious effects independent of injury severity, shock, and the vicious triad. Better understanding of the biochemical mechanisms of acute traumatic coagulopathy may facilitate biochemically targeted resuscitation strategies and improve outcomes.
  
  
  METHODS
  Prognostic and epidemiologic study, level II.
authors.affiliation: From the *Department of Surgery (M.E.K., B.M.H., M.J.C.), University of California, San Francisco, and San Francisco General Hospital, San Francisco; and Division of Biostatistics and School of Public Health (A.E.H., A.L.D.), University of California at Berkeley, Berkeley, California; Department of Surgery (J.L.S.), University of Pittsburgh Medical Center and Presbyterian University Hospital, Pittsburgh, Pennsylvania; Department of Surgery (J.C., R.V.M.), University of Washington School of Medicine and Harborview Medical Center, Seattle, Washington; Department of Surgery (J.P.M.), University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas, Texas; Department of Surgery (E.E.M.), University of Colorado Health Sciences Center and Denver Health Medical Center, Denver, Colorado; and Department of Surgery (B.H.B.), Washington University School of Medicine; St. Louis, Missouri.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Kutcher
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Howard
authors.forename: Jason L
authors.initials: JL
authors.lastname: Sperry
authors.forename: Alan E
authors.initials: AE
authors.lastname: Hubbard
authors.forename: Anna L
authors.initials: AL
authors.lastname: Decker
authors.forename: Joseph
authors.initials: J
authors.lastname: Cuschieri
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Minei
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Bernard H
authors.initials: BH
authors.lastname: Brownstein
authors.forename: Ronald V
authors.initials: RV
authors.lastname: Maier
authors.forename: Mitchell Jay
authors.initials: MJ
authors.lastname: Cohen
mesh_terms: D000328:Adult; D001778:Blood Coagulation Disorders / Q000209:etiology* / Q000401:mortality; D005260:Female; D006801:Humans; D015601:Injury Severity Score; D019934:International Normalized Ratio; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology / Q000401:mortality; D011446:Prospective Studies; D012151:Resuscitation / Q000009:adverse effects*; D012307:Risk Factors; D012771:Shock, Hemorrhagic / Q000209:etiology* / Q000401:mortality; D014949:Wounds, Nonpenetrating / Q000150:complications* / Q000401:mortality