Short- and long-term effects of therapy with interferon-α and pegylated interferon-α/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. Aim: To evaluate the effect of pegylated interferon-α 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-α2a, followed by weekly administration of 180 μg of pegylated interferon-α2a/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-α2a, 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-α 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.