Pathophysiological role of prostanoids in coagulation of the portal venous system in liver cirrhosis.

Alexander Queck,Sabrina Rüschenbaum,Carsten Meyer,Katharina Maria Schwarzkopf,Frank Erhard Uschner,Robert Schierwagen,Marcus Maximilian Mücke,Joan Clària,Michael Praktiknjo,Christian Markus Lange,Christian Jansen,Jonel Trebicka,Yannick Schreiber,Stefan Zeuzem,Dominique Thomas,Gerd Geisslinger

doi:10.1371/journal.pone.0222840

Abstract

BackgroundProstanoids are important regulators of platelet aggregation and thrombotic arterial diseases. Their involvement in the development of portal vein thrombosis, frequent in decompensated liver cirrhosis, is still not investigated.MethodsTherefore, we used pro-thrombotic venous milieu generation by bare metal stent transjugular intrahepatic portosystemic shunt insertion, to study the role of prostanoids in decompensated liver cirrhosis. Here, 89 patients receiving transjugular intrahepatic portosystemic shunt insertion were included in the study, and baseline levels of thromboxane B2, prostaglandin D2 and prostaglandin E2 were measured in the portal and the hepatic vein.ResultsWhile the hepatic vein contained higher levels of thromboxane B2 than the portal vein, levels of prostaglandin E2 and D2 were higher in the portal vein (all P<0.0001). Baseline concentrations of thromboxane B2 in the portal vein were independently associated with an increase of portal hepatic venous pressure gradient during short term follow-up, as an indirect sign of thrombogenic potential (multivariable P = 0.004). Moreover, severity of liver disease was inversely correlated with portal as well as hepatic vein levels of prostaglandin D2 and E2 (all P<0.0001).ConclusionsElevated portal venous thromboxane B2 concentrations are possibly associated with the extent of thrombogenic potential in patients with decompensated liver cirrhosis.Trial registrationClinicalTrials.gov identifier: NCT03584204.

Highlights

Cirrhosis has been shown to be a pro- as well as an anticoagulatory condition[1]
89 patients receiving transjugular intrahepatic portosystemic shunt insertion were included in the study, and baseline levels of thromboxane B2, prostaglandin D2 and prostaglandin E2 were measured in the portal and the hepatic vein
While the hepatic vein contained higher levels of thromboxane B2 than the portal vein, levels of prostaglandin E2 and D2 were higher in the portal vein

Summary

Introduction

Cirrhosis has been shown to be a pro- as well as an anticoagulatory condition[1]. Portal vein thrombosis (PVT), in particular, has been described as a sign of progression in disease stage [2]. Little is known about the role of TXA2 in the portal vein and thrombosis in the portal compartment. One reason for this lack of information is that access to this compartment is difficult. Before the use of PTFE stents, bare metal stent insertion was associated with early TIPS dysfunction, mainly due to pro-thrombotic milieu generation. Blood samples were collected at first puncture of the portal vein during TIPS insertion and certain prostanoids, namely TXB2, a stable metabolite of TXA2, PGD2 and PGE2 were measured. Prostanoids are important regulators of platelet aggregation and thrombotic arterial diseases. Their involvement in the development of portal vein thrombosis, frequent in decompensated liver cirrhosis, is still not investigated

Methods

Results

Conclusion