title: Independent contributions of hypothermia and acidosis to coagulopathy in swine.
abstract: BACKGROUND
  Clinical coagulopathy occurs frequently in the presence of acidosis and hypothermia. The purpose of this study was to determine the relative contributions of acidosis and hypothermia to coagulopathy, as measured by current standard bedside and clinical laboratory analyses (i.e., bleeding time and prothrombin time). In addition, we investigated possible mechanisms of these effects using a modified prothrombin time test, thromboelastography, and thrombin kinetics analyses. An improved understanding of coagulopathy should facilitate hemorrhage control.
  
  
  METHODS
  Twenty-four pigs were randomly allocated into normal (pH, 7.4; 39 degrees C), acidotic (pH, 7.1; 39 degrees C), hypothermic (pH, 7.4; 32 degrees C), and acidotic and hypothermic (pH, 7.1; 32 degrees C) combined groups. Acidosis was induced by the infusion of 0.2N hydrochloric acid in lactated Ringer's solution. Hypothermia was induced by using a blanket with circulating water at 4 degrees C. Development of a clinical coagulopathy was defined as a significant increase in splenic bleeding time. Measurements were compared before (pre) and 10 minutes after (post) the target condition was achieved.
  
  
  RESULTS
  Acidosis, hypothermia, or both caused the development of coagulopathy, as indicated by 47%, 57%, and 72% increases in splenic bleeding time (p < 0.05, pre vs. post). Plasma fibrinogen concentration was decreased by 18% and 17% in the acidotic and combined groups, respectively, but not in the hypothermic group. Hypothermia caused a delay in the onset of thrombin generation, whereas acidosis primarily caused a decrease in thrombin generation rates. At 4 minutes' quench time, thrombin generation in the acidotic, hypothermic, and combined groups were 47.0%, 12.5%, and 5.7%, respectively, of the value in the control group. There were no changes in serum tumor necrosis factor-alpha and interleukin-6 in any group during the study.
  
  
  CONCLUSIONS
  Acidosis and hypothermia cause a clinical coagulopathy with different thrombin generation kinetics. These results confirm the need to prevent or correct hypothermia and acidosis and indicate the need for improved techniques to monitor coagulopathy in the trauma population.
authors.affiliation: U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas 78234, USA.
authors.forename: Wenjun Z
authors.initials: WZ
authors.lastname: Martini
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pusateri
authors.forename: John M
authors.initials: JM
authors.lastname: Uscilowicz
authors.forename: Angel V
authors.initials: AV
authors.lastname: Delgado
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
mesh_terms: D000138:Acidosis / Q000097:blood* / Q000150:complications* / Q000503:physiopathology; D000818:Animals; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology; D001794:Blood Pressure; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000032:analysis; D006339:Heart Rate; D007035:Hypothermia / Q000097:blood* / Q000150:complications* / Q000503:physiopathology; D010976:Platelet Count; D012016:Reference Values; D013552:Swine; D013917:Thrombin / Q000378:metabolism; D014914:Whole Blood Coagulation Time
chemical_list: D005340:Fibrinogen; D013917:Thrombin