title: Thrombin generation and fibrin clot formation under hypothermic conditions: an in vitro evaluation of tissue factor initiated whole blood coagulation.
abstract: BACKGROUND
  Despite trauma-induced hypothermic coagulopathy being familiar in the clinical setting, empirical experimentation concerning this phenomenon is lacking. In this study, we investigated the effects of hypothermia on thrombin generation, clot formation, and global hemostatic functions in an in vitro environment using a whole blood model and thromboelastography, which can recapitulate hypothermia.
  
  
  METHODS
  Blood was collected from healthy individuals through venipuncture and treated with corn trypsin inhibitor, to block the contact pathway. Coagulation was initiated with 5pM tissue factor at temperatures 37°C, 32°C, and 27°C. Reactions were quenched over time, with soluble and insoluble components analyzed for thrombin generation, fibrinogen consumption, factor (f)XIII activation, and fibrin deposition. Global coagulation potential was evaluated through thromboelastography.
  
  
  RESULTS
  Data showed that thrombin generation in samples at 37°C and 32°C had comparable rates, whereas 27°C had a much lower rate (39.2 ± 1.1 and 43 ± 2.4 nM/min vs 28.6 ± 4.4 nM/min, respectively). Fibrinogen consumption and fXIII activation were highest at 37°C, followed by 32°C and 27°C. Fibrin formation as seen through clot weights also followed this trend. Thromboelastography data showed that clot formation was fastest in samples at 37°C and lowest at 27°C. Maximum clot strength was similar for each temperature. Also, percent lysis of clots was highest at 37°C followed by 32°C and then 27°C.
  
  
  CONCLUSIONS
  Induced hypothermic conditions directly affect the rate of thrombin generation and clot formation, whereas global clot stability remains intact.
authors: Departments of Biochemistry and Surgery, College of Medicine, University of Vermont, Burlington, VT. Electronic address: Matthew.whelihan@uvm.edu.
authors: Matthew F
authors: MF
authors: Whelihan
authors: Departments of Biochemistry and Surgery, College of Medicine, University of Vermont, Burlington, VT. Electronic address: Armin.Kiankhooy@vtmednet.org.
authors: Armin
authors: A
authors: Kiankhooy
authors: Departments of Biochemistry and Surgery, College of Medicine, University of Vermont, Burlington, VT. Electronic address: Kathleen.brummel@uvm.edu.
authors: Kathleen E
authors: KE
authors: Brummel-Ziedins
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000502:physiology*; D001780:Blood Coagulation Tests; D005176:Factor XIII / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000096:biosynthesis*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007035:Hypothermia / Q000097:blood / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D013696:Temperature; D013916:Thrombelastography; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; D013917:Thrombin
keywords: Fibrin formation; Hypothermia; Lysis; Thrombin generation; Trauma