title: Incident severe thrombocytopenia in veterans treated with pegylated interferon plus ribavirin for chronic hepatitis C infection.
abstract: OBJECTIVE
  We sought to determine the incidence and risks for severe thrombocytopenia (platelets < 50,000/μL) in United States Veteran patients treated with pegylated interferon (PEG-IFN) plus ribavirin for hepatitis C virus-positive (HCV) chronic liver disease (CLD).
  
  
  METHODS
  Using a retrospective, observational cohort study design to analyze databases from the New England Veterans Healthcare System, we identified 979 patients diagnosed with HCV-positive CLD treated solely with PEG-IFN plus ribavirin. The cohort was stratified by pre-treatment platelet counts of 50,000-100,000/μL (N = 90), >100,000-150,000/μL (N = 162), and >150,000μL (N = 727). The cumulative incidence of severe thrombocytopenia and major bleeding events were determined for each baseline platelet group for 48 weeks following treatment initiation. Multivariable Cox regression was used to identify risk factors for incident severe thrombocytopenia.
  
  
  RESULTS
  Overall, severe thrombocytopenia occurred in 6.1% (N = 60), but in 41.1% of patients with pre-treatment platelet counts 50, 000-100,000/μL compared with 11.7% (p < 0.001) and 0.55% (p < 0.001) in the two higher pre-treatment platelet groups. Most episodes occurred within the first 12 weeks of treatment. Median nadir count for these 60 patients was 35,000/μL (inter-quartile range 28,000, 44,000). Baseline platelet counts of 50,000-100,000/μL [adjusted hazard ratio (HR) = 3.81; 95%CI = 2.07-7.00] and hemoglobin <10 g/dL (adjusted HR = 3.39; 95%CI = 1.45-7.960) associated with severe thrombocytopenia. Major bleeding events during the 48-week observation period were rare (N = 5, 0.51%).
  
  
  CONCLUSIONS
  The incidence of severe thrombocytopenia in a large, observational cohort of veteran patients with HCV CLD treated with PEG-IFN plus ribavirin was 6.1%. Low pre-treatment platelet counts and hemoglobin levels associated with early, incident severe thrombocytopenia.
authors.affiliation: VA Cooperative Studies Program, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Hermos
authors.forename: Lien
authors.initials: L
authors.lastname: Quach
authors.forename: David R
authors.initials: DR
authors.lastname: Gagnon
authors.forename: H Christian
authors.initials: HC
authors.lastname: Weber
authors.forename: Arman
authors.initials: A
authors.lastname: Altincatal
authors.forename: Kelly
authors.initials: K
authors.lastname: Cho
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Lawler
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Grotzinger
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000453:epidemiology* / Q000209:etiology; D014481:United States; D014728:Veterans
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: hepatitis C; interferon; pharmacoepidemiology; thrombocytopenia; veterans