title: The acute coagulopathy of trauma is due to impaired initial thrombin generation but not clot formation or clot strength.
abstract: BACKGROUND
  Acute coagulopathy of trauma (ACOT) has been described as a very early hypocoagulable state, but the mechanism remains controversial. One proposed mechanism is tissue hypoperfusion leading to protein C activation, with subsequent inhibition of Factors V and VIII. Variability in trauma has impeded the use of clinical data towards the elucidation of the mechanisms of ACOT, but thrombelastography (TEG) may provide insight by assessing hemostatic function from initial thrombin activation to fibrinolysis. We hypothesized that in a controlled animal model of trauma/hemorrhagic shock, clotting factor dysfunction is the predominant mechanism in early ACOT.
  
  
  METHODS
  Rats anesthetized by inhaled isoflurane (n = 6) underwent laparotomy, and hemorrhage was induced to maintain a MAP of 35 mm Hg for 30 min. Rats were then resuscitated with twice their shed blood volume in normal saline. TEG was performed at baseline, shock, and post-resuscitation periods. No heparin was given. Statistical analysis was performed by ANOVA with post-hoc Fisher's test.
  
  
  RESULTS
  Coagulation factor function was significantly impaired in the early stages of trauma/hemorrhagic shock. TEG R and SP-values were significantly increased from baseline to shock (P < 0.001) and from shock to post-resuscitation periods (P < 0.05). Delta (R-SP), a measure of thrombin generation, showed a significant increase (P < 0.05) from baseline to shock. No significant changes were found in K, Angle, MA, and LY30 values.
  
  
  CONCLUSIONS
  Clotting factor derangement leading to impaired thrombin generation is the principle etiology of ACOT in this model and not the dynamics of clot formation, fibrin cross-linking, clot strength/platelet function, or fibrinolysis.
authors.affiliation: Department of Surgery, University of Colorado Denver, Aurora, Colorado, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Harr
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Max V
authors.initials: MV
authors.lastname: Wohlauer
authors.forename: Nathan
authors.initials: N
authors.lastname: Droz
authors.forename: Miguel
authors.initials: M
authors.lastname: Fragoso
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D000208:Acute Disease; D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000209:etiology*; D005342:Fibrinolysis / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000097:blood / Q000150:complications; D013916:Thrombelastography; D013917:Thrombin / Q000096:biosynthesis* / Q000378:metabolism; D014947:Wounds and Injuries / Q000097:blood* / Q000150:complications*
chemical_list: D013917:Thrombin