title: Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation.
abstract: BACKGROUND
  We developed a hemorrhagic shock animal model to replicate an urban prehospital setting where resuscitation fluids are limited to assess the effect of saline versus plasma in coagulopathic patients. An in vitro model of whole blood dilution with saline exacerbated tissue plasminogen activator (tPA)-mediated fibrinolysis, while plasma dilution did not change fibrinolysis. We hypothesize that shock-induced hyperfibrinolysis can be attenuated by resuscitation with plasma while exacerbated by saline.
  
  
  METHODS
  Sprague-Dawley rats were hemorrhaged to a mean arterial pressure of 25 mm Hg and maintained in shock for 30 minutes. Animals were resuscitated with either normal saline (NS) or platelet-free plasma (PFP) with a 10% total blood volume bolus, followed by an additional 5 minutes of resuscitation with NS to increase blood pressure to a mean arterial pressure of 30 mm Hg. Animals were observed for 15 minutes for the assessment of hemodynamic response and survival. Blood samples were analyzed with thrombelastography paired with protein analysis.
  
  
  RESULTS
  The median percentage of total blood volume shed per group were similar (NS, 52.5% vs. PFP, 55.7; p = 0.065). Survival was 50% in NS compared with 100% in PFP. The change in LY30 and tPA levels from baseline to shock was similar between groups (LY30 PFP, 10; interquartile range [IQR], 4.3-11.2; NS, 4.5; IQR, 4.1-14.2; p = 1.00; tPA PFP, 16.6 ng/mL; IQR, 13.7-27.8; NS, 22.4; IQR, 20.1-25.5; p = 0.240). After resuscitation, the median change in LY30 was greater in the NS group (13.5; IQR, 3.5-19.9) compared with PFP (-4.9%; IQR, -9.22 to 0.25 p = 0.004), but tPA levels did not significantly change (NS, 1.4; IQR, -6.2 to 7.1 vs. PFP, 1.7; IQR, -5.2 to 6.8; p = 0.699).
  
  
  CONCLUSIONS
  Systemic hyperfibrinolysis is driven by hypoperfusion and associated with increased levels of tPA. Plasma is a superior resuscitation fluid to NS in a prehospital model of severe hemorrhagic shock as it attenuates hyperfibrinolysis and improves systemic perfusion.
authors.affiliation: From the Department of Surgery (H.B.M., E.E.M., A.P.M., E.G., M.F., M.P.C., M.D., K.C.H., A.B., A.S., C.C.S.), University of Colorado Denver, Denver Health Medical Center (H.B.M., E.E.M., A.P.M., E.G., M.F., M.P.C.), and Bonfils Blood Center (C.C.S.), Denver, Colorado.
authors.forename: Hunter B
authors.initials: HB
authors.lastname: Moore
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Morton
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gonzalez
authors.forename: Miguel
authors.initials: M
authors.lastname: Fragoso
authors.forename: Michael P
authors.initials: MP
authors.lastname: Chapman
authors.forename: Monika
authors.initials: M
authors.lastname: Dzieciatkowska
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Hansen
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.forename: Angela
authors.initials: A
authors.lastname: Sauaia
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology*; D006439:Hemodynamics; D008297:Male; D010949:Plasma / Q000502:physiology*; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy*; D012965:Sodium Chloride / Q000494:pharmacology*; D013916:Thrombelastography
chemical_list: D012965:Sodium Chloride