Shock releases bile acidinducing platelet inhibition and fibrinolysis

摘要: 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 promotes fibrinolysis. Methods was exogenously added obtained from volunteers. A titration 250 μM–750 μM used due biologic relevance. Whole mixtures were assayed using thrombelastography strength (maximum amplitude [MA]) fibrinolysis (LY30) quantification. Tranexamic block plasmin-mediated Platelet microfluidics performed. proteomic analysis completed citrated plasma shock resuscitation rat model. Results Fibrinolysis increased when 750-μM (median LY30 0.08–5.7, P = 0.010) decreased MA of 53.3–43.8, P = 0.010). The addition tranexamic titration, partially reversed the induced (LY30: without 7.7 versus with 2.7) decrease in (MA: 48.2 53.2), but did not reverse effects levels. function reduced by 50% presence 100-μM TUCA. Rats had median 52-fold increase TUCA, after state stayed elevated resuscitation. Conclusions reduces reduction is attributable platelet inhibition. This metabolic coagulation warrants further investigation, as localized areas body, high levels may be at risk postoperative bleeding.