title: Erythrocyte mean corpuscular volume as a surrogate marker for 6-thioguanine nucleotide concentration monitoring in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine.
abstract: Mean corpuscular volume may correlate with erythrocyte 6-thioguanine nucleotide concentrations in patients treated with azathioprine and 6-mercaptourine. We conducted a study of 166 patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine to determine the relationship between mean corpuscular volume and erythrocyte 6-thioguanine nucleotide concentrations, disease activity as measured by the Inflammatory Bowel Disease Questionnaire (active disease <170, remission >170), and leukopenia. Blood was submitted for mean corpuscular volume, whole blood 6-thioguanine nucleotide concentration, and leukocyte count. The mean +/- SD mean corpuscular volume during treatment was 94.7 +/- 6.6 fL and the mean +/- SD change in mean corpuscular volume was 7.5 +/- 6.3 fL. There were significant correlations between mean corpuscular volume and erythrocyte 6-thioguanine nucleotide concentration (r(s) = 0.33, p < 0.001) and between change from baseline in mean corpuscular volume and erythrocyte 6-thioguanine nucleotide concentration (r(s) = 0.26, p = 0.001). There was no correlation between Inflammatory Bowel Disease Questionnaire scores and mean corpuscular volume values (r(s) = 0.01, p = 0.94). The mean corpuscular volume values in 55 patients with active disease and 111 patients in remission were similar (95.1 vs. 94.5 fL, p = 0.57). There was a weak negative correlation between the mean corpuscular volume and the leukocyte count, (r(s) = -0.18, p = 0.022). In patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine, mean corpuscular volume and change from baseline in mean corpuscular volume correlated with erythrocyte 6-thioguanine nucleotide concentrations and negatively with leukocyte counts, but did not correlate with disease activity as measured by the Inflammatory Bowel Disease Questionnaire. Measurement of mean corpuscular volume is a simple and inexpensive alternative to measurement of 6-thioguanine nucleotide concentrations in patients treated with azathioprine or 6-mercaptopurine.
authors.affiliation: Division of Gastroenterology and Hepatology, Division of Clinical Pharmacology, and Section of Biostatistics, Mayo Clinic, Rochester, MN 55905, U.S.A.
authors.forename: Carlton W
authors.initials: CW
authors.lastname: Thomas
authors.forename: Philip W
authors.initials: PW
authors.lastname: Lowry
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Franklin
authors.forename: Amy L
authors.initials: AL
authors.lastname: Weaver
authors.forename: Gennett M
authors.initials: GM
authors.lastname: Myhre
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Mays
authors.forename: William J
authors.initials: WJ
authors.lastname: Tremaine
authors.forename: James J
authors.initials: JJ
authors.lastname: Lipsky
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D023381:Endpoint Determination; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000502:physiology*; D005260:Female; D006150:Guanine Nucleotides / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy*; D007958:Leukocyte Count; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use*; D008875:Middle Aged; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013873:Thionucleotides / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006150:Guanine Nucleotides; D007166:Immunosuppressive Agents; D013873:Thionucleotides; C003964:6-thioguanylic acid; D015122:Mercaptopurine; D001379:Azathioprine