title: Short- and long-term effects of therapy with interferon-alpha and pegylated interferon-alpha/ribavirin on platelet plug formation and von Willebrand factor release in patients with chronic hepatitis C.
abstract: BACKGROUND
  A pegylated interferon-alpha-induced decrease in platelet counts may become a limiting factor for continuation of therapy.
  
  
  OBJECTIVE
  To evaluate the effect of pegylated interferon-alpha administration on platelet plug formation and von Willebrand factor antigen release in patients with chronic hepatitis C.
  
  
  METHODS
  Thirty patients with chronic hepatitis C (genotype 1; fibrosis 1-3: n = 16, cirrhosis: n = 14) received a single dose of 9 MU interferon-alpha2a, followed by weekly administration of 180 mug of pegylated interferon-alpha2a/ribavirin for 48 weeks. Platelet counts, platelet function (collagen-epinephrine-induced closure time) and von Willebrand factor antigen were measured.
  
  
  RESULTS
  Platelet counts and collagen-epinephrine-induced closure time decreased by 13% and 16%, respectively, 24 h after the first dose of interferon-alpha2a, and von Willebrand factor antigen levels increased by 31% (P < 0.01) compared with baseline. During a 48-week observation period, platelet counts decreased by a maximum of 33% (P < 0.001), von Willebrand factor antigen levels increased by 69% (P < 0.001) whereas collagen-epinephrine-induced closure time did not change. In noncirrhotic patients, the increase of von Willebrand factor antigen levels was maintained throughout therapy without a change in collagen-epinephrine-induced closure time. In contrast, in cirrhotics, von Willebrand factor antigen levels did not increase, while collagen-epinephrine-induced closure time was prolonged.
  
  
  CONCLUSIONS
  Single-dose interferon-alpha decreases platelet counts but improves platelet function, possibly by the release of von Willebrand factor antigen. Accordingly, long-term antiviral treatment had no effect on collagen-epinephrine-induced closure time, despite the decrease in platelet count in noncirrhotic patients. Such a compensation of decreased platelet counts by increased von Willebrand factor antigen level did not occur in cirrhotics.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine IV, Medical University, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Homoncik
authors.forename: A
authors.initials: A
authors.lastname: Ferlitsch
authors.forename: P
authors.initials: P
authors.lastname: Ferenci
authors.forename: E
authors.initials: E
authors.lastname: Formann
authors.forename: B
authors.initials: B
authors.lastname: Jilma
authors.forename: A
authors.initials: A
authors.lastname: Gangl
authors.forename: S
authors.initials: S
authors.lastname: Panzer
authors.forename: M
authors.initials: M
authors.lastname: Peck-Radosavljevic
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a