title: Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event.
abstract: BACKGROUND
  In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.
  
  
  METHODS
  We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n=47), Budd-Chiari syndrome (BCS, n=15) and cirrhosis (n=24) and compared the results to those obtained from healthy controls (n=21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].
  
  
  RESULTS
  There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p=0.006 for endogenous thrombin potential (ETP) and p<0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p=0.001, p=0.006, p<0.001, p<0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p=0.044) and peak (p=0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p=0.001).
  
  
  CONCLUSIONS
  Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Medicine, Division of Haematology, Coagulation Unit, Karolinska University Hospital, Stockholm, Sweden. Electronic address: roza.chaireti@karolinska.se.
authors.forename: Roza
authors.initials: R
authors.lastname: Chaireti
authors.affiliation: Center for Digestive Diseases, Division of Hepatology, Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Department of Medicine, Solna, Sweden.
authors.forename: Rupesh
authors.initials: R
authors.lastname: Rajani
authors.affiliation: Center for Digestive Diseases, Division of Hepatology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Bergquist
authors.affiliation: Division of Gastroenterology & Hepatology, University Hospital, Lund, Sweden.
authors.forename: Tor
authors.initials: T
authors.lastname: Melin
authors.affiliation: Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Inga-Lill
authors.initials: IL
authors.lastname: Friis-Liby
authors.affiliation: Karolinska Institutet, Department of Clinical Sciences Danderyd Hospital, Division of Medicine, Stockholm, Sweden.
authors.forename: Marjo
authors.initials: M
authors.lastname: Kapraali
authors.affiliation: Department of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden; Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Stergios
authors.initials: S
authors.lastname: Kechagias
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Tomas L
authors.initials: TL
authors.lastname: Lindahl
authors.affiliation: Karolinska Institutet, Department of Medicine, Solna, Sweden; Center for Digestive Diseases, Division of Gastroenterology, Karolinska University hospital, Stockholm, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Almer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D001780:Blood Coagulation Tests; D006502:Budd-Chiari Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006487:Hemostasis; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013152:Splanchnic Circulation; D013917:Thrombin / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism; D020246:Venous Thrombosis / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D014859:Warfarin / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D018180:Thrombomodulin; D014859:Warfarin; D013917:Thrombin
keywords: Budd-Chiari syndrome; Cirrhosis; Portal vein thrombosis; Thrombin generation; Thrombomodulin