Background & Aims: Chronic HCV patients with baseline thrombocytopenia are often excluded from treatment with peginterferon alfa and ribavirin or undergo many dose reductions of peginterferon alfa. The aim of this study was to investigate the correlation between thrombocytopenia and the occurrence of bleedings during antiviral treatment for HCV infection. Methods: In this single center cohort study 2876 visits of 321 patients treated with peginterferon alfa and ribavirin were evaluated for thrombocytopenia, bleedings and dose reductions during HCV treatment. Results: Mean platelet count at baseline was 207,000/mu l for non-cirrhotic patients (n = 253) and 132,000/mu l for cirrhotic patients (n = 68). Mean platelet drop was 42% from 191,000 to 113,100/mu l (range 8000-284,000/mu l). Severe thrombocytopenia (platelet counts <50,000/mu l) was observed in 30 patients (9.3%) at 166 visits and 9 patients developed platelet counts <25,000/mu l at 15 visits. Forty-eight bleedings were observed in 27 patients (8.4%). Only one bleeding, due to gastrointestinal angiodysplasia, was defined as severe. However, this patient did not have severe thrombocytopenia at the time of bleeding. During visits, patients reported more minor bleedings when platelet counts were <50,000/mu l compared to visits with platelet counts >= 50,000/mu l (11.4% vs. 1.1%, p < 0.001). In the multivariate analysis, platelet count of <50,000/mu l was a significant predictor of bleeding (p < 0.001). Conclusions: Severe bleedings did not occur in patients with platelet counts below 50,000/mu l; based on these findings, treatment with peginterferon alfa and ribavirin appears to be safe in patients with platelet counts below 50,000/mu l although platelet counts below 25,000/mu l were rare. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.