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

PLoS One. 2019 Oct 23;14(10):e0222840. doi: 10.1371/journal.pone.0222840. eCollection 2019.

Abstract

Background: 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: Therefore, 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.

Results: 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 (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).

Conclusions: Elevated portal venous thromboxane B2 concentrations are possibly associated with the extent of thrombogenic potential in patients with decompensated liver cirrhosis.

Trial registration: ClinicalTrials.gov identifier: NCT03584204.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Coagulation / drug effects*
  • Female
  • Humans
  • Liver Cirrhosis / blood*
  • Liver Cirrhosis / physiopathology*
  • Male
  • Middle Aged
  • Portal Pressure / drug effects
  • Portal Vein / drug effects
  • Portal Vein / physiopathology*
  • Portasystemic Shunt, Transjugular Intrahepatic
  • Prostaglandins / blood*
  • Regression Analysis
  • Survival Analysis

Substances

  • Prostaglandins

Associated data

  • ClinicalTrials.gov/NCT03584204

Grant support

This study was supported by Deutsche Forschungsgemeinschaft SFB TRR57 P18 to Jonel Trebicka; Deutsche Forschungsgemeinschaft CRC1382 to Jonel Trebicka; H2020 European Institute of Innovation and Technology 668031 to Jonel Trebicka; H2020 European Institute of Innovation and Technology 825694 to Jonel Trebicka; H2020 Societal Challenges 731875 to Jonel Trebicka; CELLEX Foundation PREDICT to Jonel Trebicka; Deutsche Forschungsgemeinschaft LA 2806/2-1 to Christian Markus Lange; Deutsche Forschungsgemeinschaft LA 2806/5-1 to Christian Markus Lange; Deutsche Forschungsgemeinschaft SFB 1039/Z01 to Gerd Geisslinger. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.