Mean Corpuscular Volume to White Blood Cell Ratio for Thiopurine Monitoring in Pediatric Inflammatory Bowel Disease

Abstract

Objectives:Thiopurines, commonly used to treat inflammatory bowel disease, cause lymphopenia and red blood cell macrocytosis, requiring therapeutic monitoring. Mean corpuscular volume/white blood cell (MCV/WBC) ratio has been proposed as a surrogate for therapeutic monitoring. Our aim was to investigate MCV/WBC ratio for assessing clinical response to thiopurines among pediatric patients with inflammatory bowel disease.Methods:We performed a retrospective cross-sectional study at a tertiary care center using laboratory results and standardized physician global assessments (PGA) among pediatric patients taking thiopurines. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, and 6-thioguanine nucleotides were assessed when available. The primary outcome was association between MCV/WBC ratio and clinical remission assessed by ESR, CRP, calprotectin, or PGA. We also used a composite outcome requiring all available data to be normal. Analyses were limited to 1 occurrence per patient, >60 days after starting thiopurine, and comparators were required to be within 14 days of one another.Results:A total of 471 patients met inclusion criteria. MCV/WBC ratio poorly predicted quiescent disease as defined by PGA (area under receiver operating characteristic curve [AuROC] 0.55, 95% confidence interval [CI] 0.43–0.66). MCV/WBC ratio better predicted quiescent disease defined as normal CRP (AuROC 0.64, 95% CI 0.58–0.70) or normal ESR (AuROC 0.59, 95% CI 0.52–0.66). When the composite outcome measure was used, MCV/WBC ratio had an AuROC of 0.65 (95% CI 0.59–0.70), indicating it is reasonably accurate in discriminating between clinical remission and active disease.Conclusions:MCV/WBC ratio is a noninferior, easy, and low-cost alternative to thiopurine metabolite monitoring.

Safety of Thiopurine Use in Paediatric Gastrointestinal Disease

“…mean corpuscular volume, red blood cell distribution width, S-albumin, hematocrit, mean corpuscular hemoglobin concentration, platelet count, serum iron, transferrin saturation) and including age, and sex, models have been proposed in children, as an alternative to the more expensive thioguanine metabolite monitoring, for predicting patients with low 6-TGN and AZA treatment non-adherence. Nevertheless, these models cannot fully substitute standard measurement of intracellular metabolites in erythrocytes (34,35). However, in a large paediatric population, proactive thiopurine metabolite monitoring was not shown to impact on the durability of thiopurine monotherapy.…”

Lack of Correlation of Mean Corpuscular Volume to White Blood Cell Ratio to Thiopurine Levels

“…To the Editor: Kandavel et al (1) retrospectively investigated the value of mean corpuscular volume to white blood cell (MCV/WBC) ratio as estimates for 6‐TG levels, and further as surrogate marker for thiopurine efficacy in pediatric inflammatory bowel disease (PIBD) patients treated with thiopurine in their center. Their analysis was based on 440 PIBD patients with complete blood cell count, 441 patients with ESR or CRP values, 111 patients with physician global assessment (PGA) evaluation, but only 53 patients with 6‐TG levels available.…”

Response to Letter on “Lack of Correlation of Mean Corpuscular Volume to White Blood Cell Ratio to Thiopurine Levels” by Dr de Laffolie

“…As clinicians would recognize, microcytic anemia is often associated with ongoing disease activity, and obviates the need for such surrogates as MCV/WBC ratio (6). Therefore, the MCV/WBC ratio is most relevant to nonanemic patients, in whom the performance is better than reported in our original study (2).…”

“…To the Editor : We appreciate Dr de Laffolie and colleagues’ interest in our study (1,2). The authors made several important points we feel should be addressed.…”

“…They evaluated 226 pediatric patients with inflammatory bowel disease, and found there was no significant association between the mean corpuscular volume to white blood cell (MCV/WBC) ratio or 6‐thioguanine (6‐TGN) levels and physical global assessment (PGA) (2). This corroborates the findings from our study and is consistent with other literature that has demonstrated poor predictive valuate of 6‐TGN levels in thiopurine drug monitoring (3).…”