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

Vincenzo La Mura, Armando Tripodi, Giulia Tosetti, Flaminia Cavallaro, Veena Chantarangkul, Massimo Colombo, Massimo Primignani

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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.

Original languageEnglish
JournalLiver International
Publication statusAccepted/In press - 2016


  • Cirrhosis
  • Coagulation
  • Portal hypertension
  • Portal vein thrombosis
  • Survival

ASJC Scopus subject areas

  • Hepatology


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