Shock releases bile acid inducing platelet inhibition and fibrinolysis

The Journal of Surgical Research
Gregory WienerAnirban Banerjee

Abstract

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. 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. 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 10...Continue Reading

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Citations

Oct 21, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Leonardo A MoraesJonathan M Gibbins
Apr 2, 2019·Annals of the American Thoracic Society·Camille R PetriAsha Anandaiah
Apr 16, 2019·Journal of Thrombosis and Haemostasis : JTH·Lucy Z KornblithMitchell J Cohen
May 4, 2017·The Journal of Trauma and Acute Care Surgery·Nathan ClendenenAngelo DʼAlessandro
Oct 26, 2018·The Journal of Trauma and Acute Care Surgery·Ernest E Moore
Dec 8, 2020·Biomedical Chromatography : BMC·Ping XuXinru Liu
Jul 9, 2021·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Pijun YanRan Liu

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