Hematologic Indices as Surrogate Markers for Monitoring Thiopurine Therapy in IBD

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• 作者：Uri Kopylov ; Robert Battat ; Amine Benmassaoud…
• 关键词：Thiopurines ; 6 ; Thioguanine ; Macrocytosis ; Leukopenia
• 刊名：Digestive Diseases and Sciences
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：60
• 期：2
• 页码：478-484
• 全文大小：183 KB
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  15. Thomas CW Jr, Lowry PW, Franklin CL, et al. 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. / Inflam Bowel Dis. 2003;9:237-45. CrossRef
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• 作者单位：Uri Kopylov (1) (2)
  Robert Battat (1) (2)
  Amine Benmassaoud (1) (2)
  Laurence Paradis-Surprenant (1) (2)
  Ernest G. Seidman (1) (2)
  
  1. Division of Gastroenterology, McGill University Health Centre, Montreal, QC, Canada
  2. Faculty of Medicine, McGill University, Montreal, QC, Canada
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Gastroenterology
  Hepatology
  Oncology
  Transplant Surgery
  Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-2568

文摘

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. Aims 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?×?108 erythrocytes and 6-mmp levels >5,700?pmol/8?×?108 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. Conclusion 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.