Change in Hematologic Indices over Time in Pediatric Inflammatory Bowel Disease Treated with Azathioprine

Abstract

Azathioprine leads to changes in mean corpuscular volume (MCV) and white blood cell (WBC) indices reflecting efficacy or toxicity. Understanding the interactions between bone marrow stem cells and azathioprine could highlight abnormal response patterns as forerunners for hematologic malignancies. This study gives a statistical description of factors influencing the relationship between MCV and WBC in children with inflammatory bowel disease treated with azathioprine. We found that leukopenia preceded macrocytosis. Macrocytosis is therefore not a good predictor of leukopenia. Further studies will be necessary to determine the subgroup of patients at increased risk of malignancies based on bone marrow response.

Long‐term effect of NUDT15 R139C on hematologic indices in inflammatory bowel disease patients treated with thiopurine

“…This result is consistent with a previous study reporting that MCV values at 10 weeks after initiating thiopurine were significantly higher in patients with the heterozygous variant alleles of NUDT15 than in those without . Several studies suggest that thiopurine‐mediated inhibition of DNA synthesis in bone marrow precursor cells leads to megaloblastic erythropoiesis . MCV elevation above 7 fl is reported to be an indicator of optimal 6‐thioguanine nucleotide (6‐TGN) levels .…”

Thiopurine monitoring in children with inflammatory bowel disease: a systematic review

“…Fifteen studies fulfilled the eligibility criteria . ‘Potentially’ eligible studies which were assessed and subsequently excluded are shown in http://onlinelibrary.wiley.com/doi/10.1111/bcp.12365/suppinfo.…”

“…Study findings were stratified for patients, according to disease stage, blood test results, patient characteristics, concomitant medications and median treatment duration. Clinical outcome definitions were clearly described in all but three studies . The characteristics and findings of the included studies are summarized in http://onlinelibrary.wiley.com/doi/10.1111/bcp.12365/suppinfo.…”

Hematologic Indices as Surrogate Markers for Monitoring Thiopurine Therapy in IBD

“…The pathophysiology of this phenomenon is not completely clear, but it has been suggested that it results from inhibition of DNA synthesis leading to megaloblastic erythropoiesis [14,15,17]. The prevalence and degree of macrocytosis may be dependent on the specific polymorphisms in the enzymatic pathway of thiopurine metabolism.…”

“…Alternative and widely available surrogate biomarkers that reflect intracellular thiopurine levels have thus been sought. Several hematologic biomarkers such as mean corpuscular volume (MCV), white blood cell, leukocyte count and platelet count have been evaluated for that purpose with conflicting results [11][12][13][14][15]. Guiding thiopurine treatment by appearance of leukopenia or macrocytosis is still a common practice [16].…”