title: Erythropoietin treatment is associated with more severe thrombocytopenia in patients with chronic hepatitis C undergoing antiviral therapy.
abstract: BACKGROUND
  Erythropoietin (EPO) not only stimulates erythropoiesis but also thrombopoiesis. As pegylated-interferon-alpha(PEG-IFN-alpha)-induced thrombocytopenia may become a limiting factor for continuation of therapy, the present study investigated if EPO can alleviate PEG-IFN-alpha induced thrombocytopenia. Further, we hypothesize that EPO increases platelet reactivity and protease activated receptor 1 (PAR-1) expression during combination antiviral therapy.
  
  
  METHODS
  Forty patients with chronic hepatitis C received either 10,000 IU EPO 3 x/week or placebo in a randomized, placebo-controlled, double-blinded fashion for 4 wk and combination antiviral therapy with PEG-IFN-2a and ribavirin.
  
  
  RESULTS
  EPO alleviated the decrease in hemoglobin during combination antiviral therapy with ribavirin (10%vs 20%, p < 0.0001). Platelet counts decreased stronger in EPO than in placebo group on day 28 (p= 0.007). EPO induced a 40% increase in PAR-1 (p < 0.0001), which was accompanied by 100% increase in platelet reactivity (p < 0.0001). PFA-100 platelet plug formation time and PEG-IFN-alpha-induced vWF-increase were not different between study groups.
  
  
  CONCLUSIONS
  Treatment with EPO alleviated the decrease in hemoglobin but worsened PEG-IFN-alpha induced thrombocytopenia after the first 4 wk of combination therapy. EPO caused PAR-1 receptor upregulation on platelets, which promoted an increase in platelet reactivity without affecting PFA-100 platelet plug formation time. EPO is not a useful option for short-term support of platelet production during antiviral therapy.
authors.affiliation: Department of Internal Medicine IV, Division of Gastroenterology, Medical University Vienna, Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Homoncik
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sieghart
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Formann
authors.forename: Monika
authors.initials: M
authors.lastname: Schmid
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Alfred
authors.initials: A
authors.lastname: Gangl
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001772:Blood Cell Count; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D044463:Receptor, PAR-1 / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D019007:P-Selectin; D044463:Receptor, PAR-1; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a