Resistance to thrombomodulin is associated with de novo portal vein thrombosis and low survival in patients with cirrhosis

Liver Int. 2016 Sep;36(9):1322-30. doi: 10.1111/liv.13087. Epub 2016 Mar 31.

Abstract

Background & aims: Portal vein thrombosis (PVT) is frequently observed in cirrhosis and may be a clinically important complication. In vitro assays for endogenous thrombin potential (ETP) demonstrated that in cirrhosis plasma has intrinsic resistance to the anticoagulant action of thrombomodulin (TM-R). This study retrospectively explores the association of TM-R with de novo PVT and its clinical impact on cirrhosis.

Methods: Fifty-three patients with cirrhosis were tested for ETP-ratio with/without thrombomodulin. Clinical, endoscopic variables, presence/absence of PVT by Doppler-US and/or CT examination were collected at baseline and up to 4 years from baseline. The de novo PVT was the primary clinical end-point. Portal hypertension (PHT)-related complications and transplantation free survival were secondary end-points. ETP-ratio higher than the 95° percentile of the distribution in 173 healthy controls defined TM-R.

Results: During 48 months of follow-up, 11 patients developed de novo PVT, with preference for the 36 patients with TM-R after adjusting for Child-Pugh class (HR: 8.354; 90%CI:1.475 - 47.305; P = 0.009). Seventeen patients experienced PHT-related complications, 23 either died or underwent liver transplantation. PHT complications and transplantation free survival were associated with TM-R, but were independently predicted by Child-Pugh class, only. Same results were obtained by considering the MELD score.

Conclusions: Owing to PVT results from the pro-coagulant imbalance occurring in patients with advanced cirrhosis, TM-R might serve as a predictor and could possibly be a biological mediator of adverse outcome in patients with advanced cirrhosis.

Keywords: cirrhosis; coagulation; portal hypertension; portal vein thrombosis; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Coagulation Tests
  • Case-Control Studies
  • Cross-Sectional Studies
  • Drug Resistance*
  • Female
  • Humans
  • Hypertension, Portal / epidemiology*
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / surgery
  • Liver Transplantation
  • Male
  • Middle Aged
  • Portal Vein / physiopathology
  • Retrospective Studies
  • Survival Analysis
  • Thrombin / analysis
  • Thrombomodulin / therapeutic use*
  • Tomography, X-Ray Computed
  • Ultrasonography, Doppler, Color
  • Venous Thrombosis / blood
  • Venous Thrombosis / etiology*

Substances

  • Biomarkers
  • Thrombomodulin
  • Thrombin