title: Effects of In vitro hemodilution, hypothermia and rFVIIa addition on coagulation in human blood.
abstract: BACKGROUND
  Coagulopathy can occur after hemorrhage, trauma and resuscitation, and has been associated with dilution of coagulation factors and hypothermia. Recombinant activated Factor VII (rFVIIa) has been used, often as a last resort, to improve hemostasis in trauma/hemorrhage patients with coagulopathy. The aim of this study was to further characterize the effects of rFVIIa on various coagulation parameters and the influence of temperature and hemodilution.
  
  
  METHODS
  WHOLE BLOOD FROM HEALTHY HUMAN VOLUNTEERS WAS INCUBATED IN A COMBINATION OF THREE CONDITIONS: undiluted or diluted 40% with either lactated Ringer's solution or Hextend, at 37°C or 34°C, and with and without rFVIIa (1.26 μg/ml, final concentration). Blood or plasma, as appropriate, was measured for coagulation by thrombin generation, thromboelastography (TEG), prothrombin Time (PT) and activated partial thromboplastin (aPTT).
  
  
  RESULTS
  Incubation of plasma at 34°C significantly elevated thrombin generation, and prolonged PT and aPTT. Dilution of blood or plasma with 40% Hextend, but not lactated Ringer's, had a significant effect on TEG parameters, and prolonged PT and aPTT. In control conditions (37°C, 0 dilution), the addition of rFVIIa to human plasma or whole blood led to a significant change in all TEG parameters, and Lagtime for thrombin generation, but not to PT or aPTT.
  
  
  CONCLUSIONS
  Theses data show that thrombin generation is affected by hypothermia, but not 40% dilution. TEG is affected by 40% dilution with Hextend, but not by hypothermia. PT and aPTT are significantly affected by both hypothermia and dilution. Recombinant FVIIa caused a greater change in thrombin generation at 34°C as compared to 37°C, and a greater change in PT at 40% dilution, suggesting that the effect of rFVIIa on coagulation is both temperature and dilution dependant.
authors.affiliation: US Army Institute of Surgical Research Fort Sam Houston, Texas 78234, USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Darlington
authors.forename: Igor
authors.initials: I
authors.lastname: Kremenevskiy
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pusateri
authors.forename: Michael R
authors.initials: MR
authors.lastname: Scherer
authors.forename: Chriselda G
authors.initials: CG
authors.lastname: Fedyk
authors.forename: Bijan S
authors.initials: BS
authors.lastname: Kheirabaldi
authors.forename: Angel V
authors.initials: AV
authors.lastname: Delgado
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dubick