Abstract

Abstract Background Anaemia is frequent in patients with IBD. Iron deficiency anaemia [IDA] and anaemia of chronic disease [ACD] are the most common subtypes and warrant a different treatment approach. The ESPGHAN/ NASHGAN position paper on Anaemia in Children with IBD describes cut-off values on ferritin, transferrin saturation [TSAT] and ferritin index (soluble transferrin receptor/log10(ferritin)) [sTfR-F], to distinguish between IDA and ACD. However, cut-off values for sTfR-F and hepcidin are based on adult data. In this exploratory study we used a data driven approach to define different anaemia groups, using hepcidin and sTfR-F and studied differences between groups and their response to iron suppletion therapy. Insights contribute to a better description of ACD and IDA in a pediatric population. Methods Data from the multi-centre prospective POPEYE study (NTR4487) consisting of a paediatric IBD population was used. Subjects with anaemia (haemoglobin [Hb] < 2 standard deviations [SD] below the mean of a healthy age reference group) with baseline ferritin, TSAT, hepcidin, sTfR-F and erythrocyte sedimentation rate [ESR] values were selected. Summary statistics of these biomarkers were generated for the data-driven groups and compared with existing characteristics for IDA and ACD groups. At baseline subjects received oral or intravenous iron repletion therapy, Hb was determined at baseline and 1 month after iron therapy. Kmeans was used, an unsupervised clustering algorithm using Euclidean distance, to divide data points into k clusters based on sTfR-F and hepcidin. Results Mean age was 13.6 (2.5 SD) years, and mean standardized Hb value -3.2 at baseline for 47 subjects. Data driven groupings using Kmeans (k=3) were based on baseline hepcidin and sTfR-F (figure 1). Group 1 shows characteristics indicative for IDA, with mean ferritin <15µg/l, TSAT < 20% and sTfR-F > 2. Group 2 shows signs suggestive for inflammation since ferritin, hepcidin and ESR were increased (mean ESR 28,5 mm/h [23,2 SD]); this group could be characterized as ACD. Group 3 could not be related to a specific anaemia type. Mean standardized Hb increase 1 month after iron repletion for 37 patients, was 2,9 (SD 0,8), 0,8 (0,7 SD), 1,3 (1,1 SD), for group 1, 2 and 3 respectively. Conclusion Explorative data-driven analysis of a real-world data set showed that hepcidin and sTfR-F can be used to characterize groups that relate to ACD and IDA in a paediatric population. Children with high sTfR-F and low hepcidin possibly benefit more from iron repletion therapy (group 1), compared to when hepcidin is high (group 2). If validated in a larger patient population this determination could contribute to the development of diagnostic algorithms that support targeted therapy.

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