title: Shock releases bile acid inducing platelet inhibition and fibrinolysis.
abstract: BACKGROUND
  Metabolites are underappreciated for their effect on coagulation. Taurocholic acid (TUCA), a bile acid, has been shown to regulate cellular activity and promote fibrin sealant degradation. We hypothesize that TUCA impairs whole blood clot formation and promotes fibrinolysis.
  
  
  METHODS
  TUCA was exogenously added to whole blood obtained from volunteers. A titration from 250 μM-750 μM was used due to biologic relevance. Whole blood mixtures were assayed using thrombelastography for clot strength (maximum amplitude [MA]) and fibrinolysis (LY30) quantification. Tranexamic acid was used to block plasmin-mediated fibrinolysis. Platelet microfluidics were performed. A proteomic analysis was completed on citrated plasma obtained from a shock and resuscitation rat model.
  
  
  RESULTS
  Fibrinolysis increased when 750-μM TUCA was added to whole blood (median LY30 0.08-5.7, P = 0.010) and clot strength decreased (median MA of 53.3-43.8, P = 0.010). The addition of tranexamic acid, to a 750-μM TUCA titration, partially reversed the induced fibrinolysis (LY30: without 7.7 versus with 2.7) and the decrease in clot strength (MA: without 48.2 versus with 53.2), but did not reverse the effects to whole blood levels. Platelet function reduced by 50% in the presence of 100-μM TUCA. Rats had a median 52-fold increase in TUCA, after a shock state that stayed elevated after resuscitation.
  
  
  CONCLUSIONS
  TUCA reduces clot strength and promotes fibrinolysis. The clot strength reduction is attributable to platelet inhibition. This metabolic effect on coagulation warrants further investigation, as localized areas of the body, with high levels of bile acid, may be at risk for postoperative bleeding.
authors.affiliation: Department of Surgery, University of Colorado Denver, Aurora, Colorado.
authors.forename: Gregory
authors.initials: G
authors.lastname: Wiener
authors.affiliation: Department of Surgery, University of Colorado Denver, Aurora, Colorado. Electronic address: hunter.moore@ucdenver.edu.
authors.forename: Hunter B
authors.initials: HB
authors.lastname: Moore
authors.affiliation: Department of Surgery, University of Colorado Denver, Aurora, Colorado; Department of Surgery, Denver Health Medical Center, Denver, Colorado.
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.affiliation: Department of Surgery, University of Colorado Denver, Aurora, Colorado.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gonzalez
authors.affiliation: Institute for Medicine & Engineering, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Scott
authors.initials: S
authors.lastname: Diamond
authors.affiliation: Institute for Medicine & Engineering, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Surgery, University of Colorado Denver, Aurora, Colorado.
authors.forename: Angelo
authors.initials: A
authors.lastname: D'Alessandro
authors.affiliation: Department of Surgery, University of Colorado Denver, Aurora, Colorado.
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
mesh_terms: D000328:Adult; D000818:Animals; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000494:pharmacology*; D014148:Tranexamic Acid / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D013656:Taurocholic Acid; D014148:Tranexamic Acid
keywords: Bile salt; Clot strength; Fibrinolysis; Platelet dysfunction; Taurocholic acid; Thrombelastography