G. D. Wiener1, H. B. Moore1, P. Lawson1, E. Gonzalez1, M. P. Chapman1, A. P. Morton1, A. Sauaia1, A. Banerjee1, E. E. Moore2 1University Of Colorado Denver,Aurora, CO, USA 2Denver Health Medical Center,Aurora, CO, USA
Introduction: Recently it has been appreciated that bile acids can promote degradation of fibrin sealant. The concept of metabolites changing coagulation may explain persistent localized bleeding from the liver despite normalization of systemic coagulation. We hypothesize that bile acid impairs whole blood clot formation and promotes fibrinolysis.
Methods: Blood was collected from healthy volunteers (n=6) into citrated tubes. Taurcholic acid (TUCA) was titrated in vitro into whole blood with a range from 250 µM to 1000 µM. This range was selected as previous literature indicated that systemic TUCA levels could exceed 600 µM. Whole blood mixtures were assayed using thrombelastography (TEG) to quantify clot strength (MA) and degree of fibrinolysis (LY30). Tranexamic acid (TXA) was used to block plasmin mediated fibrinolysis. Statistical analysis used SPSS software. Correlations between TEG parameters and concentration of TUCA were analyzed using Spearman's Rho Test, and the Wilcoxon test was used for pair-wise comparisons.
Results: Clot strength had a negative correlation to dose of TUCA (Spearman’s Rho = -0.677, p<0.001). Median whole blood MA was 56.25 (IQR 53.25-58.50), which decreased to a median MA of 42.00 (IQR 38.00-48.50) at the highest dose of TUCA. Ly30 had a positive correlation to dose of TUCA (Spearman’s Rho = 0.702, p<0.001). Median whole blood Ly30 was 1.35 (IQR 0.8-1.73), which increased to a median Ly30 of 4.0 (IQR 2.85-10.3) at the highest dose of TUCA. At a dose of 750 µM TUCA, TXA reduced Ly30 from 7.7 (IQR 5.7-14.8) to 2.9 (IQR 1.9-3.3), p=0.028, but did not have a significant effect on MA (p=0.249). At the highest dose of 1000 µM TUCA, TXA did not significantly reduce Ly30 (p=0.658) and MA was unchanged by TXA at this dose (p=0.144).
Conclusion: Bile acid has a dose response in reducing clot strength and promoting fibrinolysis. This is consistent with previous literature that bile has clot degradation properties. The reduction in clot strength also suggests platelet inhibition, which is not correctable by TXA. This metabolic effect on coagulation warrants further investigation, as localized areas of the body, particularly the liver, with high levels of bile acid may be at risk for post-operative bleeding.
