Abstract Number: PB1761
Meeting: ISTH 2020 Congress
Background: Patients with liver disease suffer from bleeding complications and thrombocytopenia but also exhibit hypercoagulability suggesting a bivalent role of platelets in liver disease. Induced cholestatic liver disease through bile duct ligation in mice leads to impaired platelet activation and thrombus formation in vitro as well as bleeding complications in vivo. It is hypothesized that increased levels of bile acids in plasma affect platelet activation and hemostasis, whereas the underlying mechanisms are not well understood.
Aims: In this study we investigated the effect of bile acids on platelet activation and hemostasis
Methods: Human and murine platelets were analyzed in in vitro and ex vivo experiments regarding the effect of a variety of common bile acids on platelet activation.
Results: The incubation of isolated murine and human platelets with bile acids resulted in reduced adhesion on a fibrinogen matrix 5, 20 and 60 minutes after adhesion as well as reduced amount of fully spreaded platelets. Flow cytometric analysis of murine and human platelets revealed a reduced P-selectin expression as well as integrin ⍺IIbβ3 activation following preincubation with different bile acids whereas bile acids alone had no effect on platelet activation. In aggregation experiments no significant differences in platelet aggregation could be detected. However, diminished platelet activation resulted in reduced thrombus formation on a collagen matrix under arterial flow conditions using human and murine whole blood which were preincubated with different bile acids. Regarding the underlying mechanism, bile acids lead to platelet inhibition through phosphorylation of vasodilator activating phosphoprotein (VASP) on serine residue 157 in a time dependent manner as shown in western blot analysis of isolated murine and human platelets.
Conclusions: These results reveal that bile acids affect platelet activation negatively and impair thrombus formation, indicating a new class of negative regulators of primary hemostasis
To cite this abstract in AMA style:Reusswig F, Wienands L, Reich M, Keitel-Anselmino V, Elvers M. Influence of Bile Acids on Hemostasis and Arterial Thrombosis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/influence-of-bile-acids-on-hemostasis-and-arterial-thrombosis/. Accessed March 4, 2024.
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