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

Aliment Pharmacol Ther. 2005 Jan 1;21(1):49-55. doi: 10.1111/j.1365-2036.2004.02305.x.

Abstract

Background: A pegylated interferon-alpha-induced decrease in platelet counts may become a limiting factor for continuation of therapy.

Aim: 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Platelets / drug effects*
  • Drug Therapy, Combination
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Platelet Adhesiveness / drug effects
  • Platelet Aggregation / drug effects
  • Platelet Count
  • Polyethylene Glycols / therapeutic use*
  • Prospective Studies
  • Recombinant Proteins
  • Ribavirin / therapeutic use*
  • von Willebrand Factor / metabolism*

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • von Willebrand Factor
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a