title: Hematologic indices as surrogate markers for monitoring thiopurine therapy in IBD.
abstract: BACKGROUND
  Clinical efficacy and risk of complications are associated with intracellular levels of thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurines (6-MMP) in patients with Crohn's disease. Therapeutic monitoring of thiopurine metabolites is not widely available. Surrogate markers such as hematologic indices (MCV, leukopenia) have been proposed.
  
  
  OBJECTIVE
  To evaluate accuracy of hematologic indices for prediction of therapeutic levels of thiopurine metabolites.
  
  
  METHODS
  A retrospective cross-sectional study. We included patients treated with thiopurines for IBD between February 2008 and November 2013. Hematologic indices were correlated with thiopurine metabolites and compared to pre-treatment levels.
  
  
  RESULTS
  A total of 168 patients with 608 measurements were included. Macrocytosis was observed in 4.5 % of the patients. On multivariate analysis, macrocytosis was associated with 6-TGN levels >235 pmol/8 × 10(8) erythrocytes and 6-mmp levels >5,700 pmol/8 × 10(8) erythrocytes. Therapeutic 6-TGN levels were associated with MCV, ΔMCV, macrocytosis and lymphocyte count. Sensitivity and Spearman's r correlation for prediction of therapeutic metabolite levels were poor for all hematologic indices.
  
  
  CONCLUSIONS
  Although macrocytosis and an elevated MCV are associated with therapeutic 6-TGN levels, the correlation is weak. None of the evaluated hematologic indices is a reliable surrogate marker for thiopurine metabolite levels.
authors.affiliation: Division of Gastroenterology, McGill University Health Centre, Montreal, QC, Canada, ukopylov@gmail.com.
authors.forename: Uri
authors.initials: U
authors.lastname: Kopylov
authors.forename: Robert
authors.initials: R
authors.lastname: Battat
authors.forename: Amine
authors.initials: A
authors.lastname: Benmassaoud
authors.forename: Laurence
authors.initials: L
authors.lastname: Paradis-Surprenant
authors.forename: Ernest G
authors.initials: EG
authors.lastname: Seidman
mesh_terms: D000893:Anti-Inflammatory Agents / Q000097:blood / Q000627:therapeutic use*; D001379:Azathioprine / Q000097:blood / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003093:Colitis, Ulcerative / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D016903:Drug Monitoring / Q000379:methods*; D004909:Erythrocyte Indices; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood; D006403:Hematologic Tests; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D015122:Mercaptopurine / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D010976:Platelet Count; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013873:Thionucleotides / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D006150:Guanine Nucleotides; D006454:Hemoglobins; D013873:Thionucleotides; C003964:6-thioguanylic acid; C010240:6-methylthiopurine; D015122:Mercaptopurine; D001379:Azathioprine