title: Thrombelastography is better than PT, aPTT, and activated clotting time in detecting clinically relevant clotting abnormalities after hypothermia, hemorrhagic shock and resuscitation in pigs.
abstract: BACKGROUND
  Hypothermia and hemorrhagic shock contribute to coagulopathy after trauma. In this study, we investigated the independent and combined effects of hypothermia and hemorrhage with resuscitation on coagulation in swine and evaluated clinically relevant tests of coagulation.
  
  
  METHODS
  Pigs (n = 24) were randomized into four groups of six animals each: sham control, hypothermia, hemorrhage with resuscitation, and hypothermia, hemorrhage with resuscitation combined. Hypothermia to 32 degrees C was induced with a cold blanket. Hemorrhage was induced by bleeding 35% of total blood volume followed by resuscitation with lactated Ringer's solution. Coagulation was assessed by thrombin generation, prothrombin time (PT), activated partial thromboplastin time (aPTT), activated clotting time (ACT), and thrombelastography (TEG) from blood samples taken at baseline and 4 hour after hypothermia and/or hemorrhage with resuscitation. Data were compared with analysis of variance.
  
  
  RESULTS
  Baseline values were similar among groups. There were no changes in any measurements in the control group. Compared with baseline values, hemorrhage with resuscitation increased lactate to 140% +/- 15% (p < 0.05). Hypothermia decreased platelets to 73% +/- 3% (p < 0.05) with no effect on fibrinogen. Hemorrhage with resuscitation reduced platelets to 72% +/- 4% and fibrinogen to 71% +/- 3% (both p < 0.05), with similar decreases in platelets and fibrinogen observed in the combined group. Thrombin generation was decreased to 75% +/- 4% in hypothermia, 67% +/- 6% in hemorrhage with resuscitation, and 75% +/- 10% in the combined group (all p < 0.05). There were no significant changes in PT or aPTT by hemorrhage or hypothermia. ACT was prolonged to 122% +/- 1% in hypothermia, 111% +/- 4% in hemorrhage with resuscitation, and 127% +/- 3% in the combined group (all p < 0.05). Hypothermia prolonged the initial clotting time (R) and clot formation time (K), and decreased clotting rapidity (alpha) (all p < 0.05). Hemorrhage with resuscitation only decreased clot strength (maximum amplitude [MA], p < 0.05). TEG parameters in the combined group reflected the abnormal R, K, MA, and alpha observed in the other groups.
  
  
  CONCLUSIONS
  Hypothermia inhibited clotting times and clotting rate, whereas hemorrhage impaired clot strength. Combining hypothermia with hemorrhage impaired all these clotting parameters. PT, aPTT were not sensitive whereas ACT was not specific in detecting these coagulation defects. Only TEG differentiated mechanism related to clotting abnormalities, and thus may allow focused treatment of clotting alterations associated with hypothermia and hemorrhagic shock.
authors.affiliation: The US Army Institute of Surgical Research, 3400 Rawley E. Chambers Avenue, Ft. Sam Houston, TX 78234, USA. wenjun.martini@amedd.army.mil
authors.forename: Wenjun Z
authors.initials: WZ
authors.lastname: Martini
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Cortez
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dubick
authors.forename: Myung S
authors.initials: MS
authors.lastname: Park
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000378:metabolism; D004195:Disease Models, Animal; D007035:Hypothermia / Q000097:blood* / Q000209:etiology / Q000628:therapy*; D010976:Platelet Count; D011237:Predictive Value of Tests; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000209:etiology / Q000628:therapy*; D013552:Swine; D013916:Thrombelastography; D014947:Wounds and Injuries / Q000097:blood* / Q000150:complications / Q000628:therapy
chemical_list: D001779:Blood Coagulation Factors