title: Resistance to thrombomodulin is associated with de novo portal vein thrombosis and low survival in patients with cirrhosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Division of Gastroenterology and Hepatology, IRCCS Ca' Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy.|Internal Medicine, IRCCS San Donato, Department of Biomedical Sciences for Health, University of Milan, Italy.
authors: Vincenzo
authors: V
authors: La Mura
authors: Department of Clinical Sciences and Community Health, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy.
authors: Armando
authors: A
authors: Tripodi
authors: Division of Gastroenterology and Hepatology, IRCCS Ca' Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy.
authors: Giulia
authors: G
authors: Tosetti
authors: Division of Gastroenterology and Hepatology, IRCCS Ca' Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy.
authors: Flaminia
authors: F
authors: Cavallaro
authors: Department of Clinical Sciences and Community Health, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy.
authors: Veena
authors: V
authors: Chantarangkul
authors: Division of Gastroenterology and Hepatology, IRCCS Ca' Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy.
authors: Massimo
authors: M
authors: Colombo
authors: Division of Gastroenterology and Hepatology, IRCCS Ca' Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy.
authors: Massimo
authors: M
authors: Primignani
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000453:epidemiology*; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011169:Portal Vein / Q000503:physiopathology; D012189:Retrospective Studies; D016019:Survival Analysis; D013917:Thrombin / Q000032:analysis; D018180:Thrombomodulin / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D018615:Ultrasonography, Doppler, Color; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology*
chemical_list: D015415:Biomarkers; D018180:Thrombomodulin; D013917:Thrombin
keywords: cirrhosis; coagulation; portal hypertension; portal vein thrombosis; survival