title: Tranexamic acid corrects fibrinolysis in the presence of acidemia in a swine model of severe ischemic reperfusion.
abstract: BACKGROUND
  Tranexamic acid (TXA) is an antifibrinolytic with anti-inflammatory properties associated with improved outcomes when administered to trauma patients at risk for bleeding; however, its efficacy is unknown in acidemia. We evaluated the efficacy of TXA on hyperfibrinolysis using an established porcine traumatic hemorrhage ischemic shock model.
  
  
  METHODS
  Ten Yorkshire swine underwent a controlled hemorrhage followed by supraceliac aortic cross-clamping. During standard resuscitation, control animals received recombinant tissue plasminogen activator (rtPA) after cross-clamp removal, and experimental animals received rtPA followed by TXA. Rotational thromboelastometry analysis was performed at baseline, 5 minutes and 15 minutes after rtPA dosing, and 4 hours after cross-clamp removal.
  
  
  RESULTS
  Control and experimental animals had similar hemodynamics and routine laboratory values at baseline and throughout resuscitation. At the time of TXA administration, average pH was 7.2. Clot formation time was prolonged from baseline and all resuscitation time points in both groups, with no difference at any time point. Maximum clot firmness decreased from baseline at all resuscitation time points in both groups. Maximum lysis increased from baseline (9% control vs. 9% TXA) after tissue plasminogen activator administration in both groups (100% control vs. 99% TXA). In experimental animals, maximum lysis returned to baseline 10 minutes after TXA administration (92% vs. 9%, p < 0.001).
  
  
  CONCLUSIONS
  TXA rapidly and fully reverses hyperfibrinolysis despite severe acidemia in a porcine trauma model. TXA is a promising adjunct to trauma resuscitation that is easily administered in austere or prehospital settings.
authors.affiliation: From the Department of Surgery (M.D., Q.H., C.R.P., S.S., M.E., M.M.), Madigan Army Medical Center, Tacoma, Washington; Legacy Emanuel Medical Center (S.I.), Portland, Oregon; and Baltimore Shock-Trauma Institute (J.D.), Baltimore, Maryland.
authors.forename: Mia
authors.initials: M
authors.lastname: DeBarros
authors.forename: Quinton
authors.initials: Q
authors.lastname: Hatch
authors.forename: Christopher Rees
authors.initials: CR
authors.lastname: Porta
authors.forename: Shashikumar
authors.initials: S
authors.lastname: Salgar
authors.forename: Seth
authors.initials: S
authors.lastname: Izenberg
authors.forename: Joseph
authors.initials: J
authors.lastname: DuBose
authors.forename: Matthew
authors.initials: M
authors.lastname: Eckert
authors.forename: Matthew
authors.initials: M
authors.lastname: Martin
mesh_terms: D000818:Animals; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005342:Fibrinolysis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000188:drug therapy; D013552:Swine; D013916:Thrombelastography; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D014148:Tranexamic Acid / Q000627:therapeutic use*; D014883:Water-Electrolyte Imbalance / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000933:Antifibrinolytic Agents; D011994:Recombinant Proteins; D014148:Tranexamic Acid; D010959:Tissue Plasminogen Activator