title: The resuscitative fluid you choose may potentiate bleeding.
abstract: BACKGROUND
  Trauma is the leading cause of death in the younger population in the United States, frequently from the development of hemorrhagic shock. Controversy exists over the type of volume resuscitation for restoring hemodynamic stability that should be used in hemorrhagic shock. Little is known about how various resuscitative paradigms affect the coagulation cascade, which is essential to controlling hemorrhagic shock.
  
  
  METHODS
  We studied the effect of various resuscitative formulas on blood coagulation using a new model of whole blood in a controlled setting with corn trypsin inhibitor and a 5-pM stimulus of tissue factor. We investigated thrombin generation, fibrin formation, and platelet activation with four diluents: 0.9% NaCl (NS), lactated Ringer's solution (LR), 6% hydroxyethyl starch (HES), and 3% NaCl (HS), each from 0% to 75% blood dilution. Thrombin generation was measured periodically during a time course of 20 minutes in its complex with antithrombin III. Platelet activation and fibrinopeptide A (FPA) release were monitored in serum at a 20-minute time point. Fibrin clots were collected and weighed.
  
  
  RESULTS
  The coagulation markers (thrombin generation, platelet activation, and FPA release) were significantly different by dilution (p < 0.001 in all) and diluent by dilution (p < 0.001 in all). Thrombin generation, platelet activation, and FPA release decreased the least with the diluents NS and LR. LR caused the least amount of variation in thrombin generation over the dilution course. HS produced the most dramatic change in all of the markers; no coagulation was seen between 30% to 75% dilution (p < 0.05). HES produced greater decreases in thrombin generation and FPA release than NS and LR. Fibrin clot mass decreased with a 10% to 20% dilution for NS and LR, whereas stable fibrin mass did not decrease with the diluents HES and HS at 10% to 20% dilutions. At >30% dilutions, HS produced no stable clots and HES dramatically decreased clot formation by 61% and maintained this level.
  
  
  CONCLUSIONS
  LR and NS had the least effect on thrombin generation, clot formation, and platelet activation at various concentrations compared with HES and HS. This observational data suggests that volume expanders such as HES and HS may be detrimental in treatment of hemorrhagic shock.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Vermont, Burlington, Vermont 05405, USA. kathleen.brummel@uvm.edu
authors.forename: Kathleen
authors.initials: K
authors.lastname: Brummel-Ziedins
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Whelihan
authors.forename: Eduards G
authors.initials: EG
authors.lastname: Ziedins
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Mann
mesh_terms: D000328:Adult; D005344:Fibrinopeptide A / Q000378:metabolism*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology*; D008875:Middle Aged; D010952:Plasma Substitutes / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D012151:Resuscitation; D000077325:Ringer's Lactate; D012965:Sodium Chloride / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism*
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D010952:Plasma Substitutes; D000077325:Ringer's Lactate; D005344:Fibrinopeptide A; D012965:Sodium Chloride; D013917:Thrombin