title: Evaluation of coagulation during treatment with directly acting antivirals in patients with hepatitis C virus related cirrhosis.
abstract: The effect of direct-acting-antivirals (DAA) on coagulation of hepatitis-C-virus (HCV)-related cirrhosis is unknown.
  
  
  
  We investigated 28 patients on DAA treatment and performed prothrombin-time, thrombin generation with and without thrombomodulin, whole-blood thromboelastometry, as well as the individual procoagulants (II, VIII, XIII, von Willebrand) and anticoagulants, antithrombin and protein-C.
  
  
  
  Patients had undetectable HCV-RNA at the end-of- treatment and at 12-weeks after end-of-treatment (sustained virological response). Transaminases were significantly decreased at both end-of-treatment and at 12-weeks. Prothrombin-time declined at 12-weeks, but did not reach statistical significance. Factor-II, protein-C and antithrombin increased significantly at end-of-treatment (P<.001) and persisted at 12-weeks. Factor-VIII decreased at end-of-treatment and to a greater extent at 12-weeks when reached statistical significance (P<.05). Factor-VIII/protein-C ratio decreased sharply, reached statistical significance at end-of-treatment (P<.01) and persisted at 12-weeks. Von-Willebrand decreased at end-of-treatment and reached statistical significance at 12-weeks (P<.001). Endogenous-thrombin-potential without thrombomodulin increased significantly at end-of-treatment (P<.01) and persisted at 12-weeks. No changes were observed after addition of thrombomodulin. Endogenous-thrombin-potential ratio (with/without thrombomodulin) decreased and reached statistical significance at 12-weeks (P<.05). Thromboelastometry clotting time decreased sharply, reached statistical significance at end-of treatment (P<.001) and persisted at 12-weeks.
  
  
  
  Treatment with DAAs in HCV-related cirrhosis results in improvement of the individual pro- and anticoagulants. It can be hypothesised that the net effect does not substantially modify their balance (as shown by the unchanged thrombin generation in the presence of thrombomodulin) but makes it more stable and less amenable to be perturbed as presumably occurs before treatment when there is a partial deficiency for both.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy.|Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milano, Italy.|IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.
authors.forename: Armando
authors.identifier: 0000-0003-1602-2776
authors.initials: A
authors.lastname: Tripodi
authors.affiliation: IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.|Division of Gastroenterology and Hepatology, Milano, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: D'Ambrosio
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy.|IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Padovan
authors.affiliation: IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.|Division of Gastroenterology and Hepatology, Milano, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Tosetti
authors.affiliation: IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.|Division of Gastroenterology and Hepatology, Milano, Italy.|Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.affiliation: IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.|Division of Gastroenterology and Hepatology, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Primignani
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy.
authors.forename: Veena
authors.initials: V
authors.lastname: Chantarangkul
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy.|IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.|Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy.
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
authors.affiliation: IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.|Division of Gastroenterology and Hepatology, Milano, Italy.|Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy.|Humanitas Clinical and Research Center, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D005260:Female; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D011517:Prothrombin Time; D000072230:Sustained Virologic Response; D013917:Thrombin / Q000032:analysis
chemical_list: D000998:Antiviral Agents; D011486:Protein C; D011516:Prothrombin; D013917:Thrombin
keywords: antithrombin; factor II; factor VIII; protein C; prothrombin time