Erythropoietin Levels in Children and Adolescents With Inflammatory Bowel Disease

Abstract

Iron deficiency anemia (IDA) and anemia of chronic disease (CDA) are often encountered in patients with inflammatory bowel disease (IBD). Inadequate intake or loss of iron is a clear cause of IDA, but mechanisms of CDA induction are multifactorial and involve erythropoiesis disturbance due to circulating inflammation mediators. The authors investigated erythropoietin (Epo) levels in children and adolescents with IBD and correlated them to disease activity, with the aim of gaining an improved understanding of the role of Epo in CDA. Thirty-three patients with IBD were examined (18 boys, 15 girls) ages 4 to 15 years (median 11 years). Two study groups related to the disease activity were formed: group A, those with active disease (n = 21), and group B, those in remission (n = 12). Epo levels were measured using a two-site chemiluminescence immunoassay. Predictive Epo values in response to the degree of anemia were calculated by the equation: logEpo = (3.48 - 0.20) x Hb. According to the results, CDA anemia was present only in patients with active disease. These patients also had a significantly higher possibility of altered Epo levels than expected compared with patients with inactive disease (16/21 vs. 4/12, P < 0.05). It was also interesting that most of the patients with anomalous Epo concentrations presented with an elevated Epo value compared with that expected from the calculation (14/20). It seems that disturbed Epo concentrations are correlated with disease activity in children and adolescents with IBD. It is possible that failure of the bone marrow to respond to increased Epo levels leads to further incremental response. These in turn lead to the high Epo concentrations detected in most of the authors' patients. Impaired Epo production is another mechanism of CDA development and is the one mainly expressed in patients with low Epo values.

Stimulating erythropoiesis in inflammatory bowel disease associated anemia

“…Serum EPO levels that are inappropriately low for the degree of anemia, indicates blunted EPO response, and is encountered in anemia of chronic disease [41] . Higher serum EPO levels have been reported in IBD patients compared to the normal population [39,42,43] . The EPO levels increase with the degree of anemia [27] .…”

“…Moreover, the concentration of EPO that is normally between 5 to 29 U/L, can increase 100-fold in the presence of severe anemia. However, in some patients, EPO concentrations fail to increase despite significant anemia [39] . Measurement of serum EPO levels is useful only in anemic patients with hemoglobin levels less than 100 g/L, since EPO levels at higher hemoglobin concentrations remain well within the normal range [40] .…”

Use of agents stimulating erythropoiesis in digestive diseases

“…There is also a variable component of anemia that is related to chronic inflammation [3,4,7,87,93] . This involves failure of iron transport that is mediated by inflammatory cytokines, such as hepcidin, which is the main negative regulator of iron absorption in the small intestine and of iron sequestration by macrophages [94][95][96][97][98][99][100][101] , and an inappropriately low production of EPO for the degree of anemia [16,90,[101][102][103] . The management of anemia in IBD should focus on proper control of the inflammatory process, as well as iron supplementation, and in cases of resistance, to assess iron therapy in combination with erythropoietic agents [3,87,91,104] .…”

“…Data from recent studies in CKD patients indicate increased morbidity and mortality in relation to high levels of hemoglobin (normal) [130][131][132][133] , as in patients with cancer [103,104] . It seems appropriate to establish a target hemoglobin level of 11-12 g/dL, which demonstrates greater benefit in quality of life and costeffectiveness in renal patients [120,133,[139][140][141][142][143][144][145] .…”

“…As well as searching for orally active formulations that will simplify the management of anemia [199][200][201][202] . There have also been negative aspects of treatment with EPO, as the cases of pure red cell aplasia [64,80] , or poor outcomes in relation to death and cardio vascular events in study of normalization of hemoglobin (in connection especially with high doses of EPO in patients with poor response) [127][128][129]137] and worse survival in patients with cancer [103,104] . However, EPO has been shown to be effective and safe in the treatment of anemia of chronic renal failure and has improved significantly quality of life of patients with chronic anemia [22][23][24][25] .…”