Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5277-5286 ◽  
Author(s):  
Igor Theurl ◽  
Elmar Aigner ◽  
Milan Theurl ◽  
Manfred Nairz ◽  
Markus Seifert ◽  
...  

Abstract The anemia of chronic disease (ACD) is characterized by macrophage iron retention induced by cytokines and the master regulator hepcidin. Hepcidin controls cellular iron efflux on binding to the iron export protein ferroportin. Many patients, however, present with both ACD and iron deficiency anemia (ACD/IDA), the latter resulting from chronic blood loss. We used a rat model of ACD resulting from chronic arthritis and mimicked ACD/IDA by additional phlebotomy to define differing iron-regulatory pathways. Iron retention during inflammation occurs in macrophages and the spleen, but not in the liver. In rats and humans with ACD, serum hepcidin concentrations are elevated, which is paralleled by reduced duodenal and macrophage expression of ferroportin. Individuals with ACD/IDA have significantly lower hepcidin levels than ACD subjects, and ACD/IDA persons, in contrast to ACD subjects, were able to absorb dietary iron from the gut and to mobilize iron from macrophages. Circulating hepcidin levels affect iron traffic in ACD and ACD/IDA and are more responsive to the erythropoietic demands for iron than to inflammation. Hepcidin determination may aid to differentiate between ACD and ACD/IDA and in selecting appropriate therapy for these patients.

2017 ◽  
Vol 7 (2) ◽  
pp. 132-137
Author(s):  
Abdul Latif ◽  
Muhammad Rafiqul Alam ◽  
Asia Khanam ◽  
Farhana Hoque ◽  
Muhammad Abdur Rahim ◽  
...  

Background: Anemia is common in patients with chronic kidney disease (CKD) and this is generally anemia of chronic disease, but iron deficiency anemia (IDA) is also common. Soluble transferrin receptor (sTfR) is a useful marker for IDA. Present study was undertaken to assess the utility of sTfR as a marker of IDA in selected group of Bangladeshi patients with CKD.Methods: This cross-sectional study was conducted in the Department of Nephrology, BSMMU, Dhaka, Bangladesh from January 2013 to December 2014. Patients with anemia admitted in nephrology department whether on hemodialysis or not and medicine department of BSMMU were taken for study. The study population was further divided into two groups; Group A, patients who are having IDA and Group B, patients with ACD and a control group was also selected. Data were collected by face to face interview and laboratory investigations with a self-administered questionnaire.Results: The mean age of the patients in two study groups were 38.40±13.23 and 34.85±10.52 years respectively and male-female ratio were 0.5:1 and 1:0.5. Mean sTfR level was higher (4.81± 1.64 ?g/ml) in patients with IDA than (2.89±1.40 ?g/ml) in patients with ACD (p <0.0001). In our study mean ferritin level was 599.59± 449.15?g/L in ACD patients whereas 101.23±119.42 in IDA patients (p<0.0001). Total iron binding capacity (TIBC) was more in ACD patients with sTfRe”3?g/ml as compared to ACD patients with sTfR<3?g/ml. Transferrin saturation (TSAT) level was significantly decreased in ACD patients with sTfR ?3?g/ml as compared to ACD patients with sTfR<3?g/ml.Conclusion: sTfR has a comparable ability to S. ferritin in diagnosing IDA and ACD. However, sTfR and serum ferritin alone cannot definitely exclude co-existing iron deficiency in ACD. As sTfR is not affected by infection and/or inflammation, thus providing a non-invasive alternative to bone marrow study.Birdem Med J 2017; 7(2): 132-137


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Gabriela Amstad Bencaiova ◽  
Alexander Krafft ◽  
Roland Zimmermann ◽  
Tilo Burkhardt

Objective.We assess and compare the efficacy of anemia treatment in pregnant women with anemia of chronic disease with true iron deficiency and in women with iron deficiency anemia.Study Design.Fifty patients with moderate anemia (hemoglobin 8.0–9.9 g/dl) and iron deficiency (ferritin < 15 μg/l) were treated in the Anemia Clinic at the Department of Obstetrics.Results.All patients showed stimulation of erythropoiesis as evidenced by an increase in reticulocyte count at day eight of therapy and showed an increase in hemoglobin and hematocrit at the end of therapy (p<0.001). The target hemoglobin (≥10.5 g/dl) was achieved in 45/50 women (90%). 12 patients showed anemia of chronic disease with true iron deficiency (12/50; 24%). Seven women (7/12; 59%) with anemia of chronic disease and iron deficiency responded well to anemia treatment. 50% of women with anemia of chronic disease and iron deficiency (3/6) responded well to intravenous iron, and 67% (4/6) responded well to the combination of intravenous iron and recombinant human erythropoietin.Conclusion.Because of frequent true iron deficiency in pregnant women with anemia of chronic disease, anemia of chronic disease in pregnancy is often falsely diagnosed as iron deficiency anemia.


Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 4142-4148 ◽  
Author(s):  
Igor Theurl ◽  
Verena Mattle ◽  
Markus Seifert ◽  
Mariagabriella Mariani ◽  
Christian Marth ◽  
...  

Anemia of chronic disease (ACD) is frequently found in patients with chronic immune activation. Since most studies on ACD pathophysiology were performed with cell culture or animal models but not in humans, we examined 37 ACD patients suffering from autoimmune diseases or infections, 10 subjects with iron-deficiency anemia (IDA), 10 anemic patients with hereditary spherocytosis (HS), and 27 age-matched controls. Although hemoglobin concentrations were comparable between ACD and IDA patients, the latter presented with significantly higher serum erythropoietin concentrations than ACD patients. The significant negative correlation between erythropoietin and hemoglobin levels observed in IDA patients was also found in a group of anemic but not hypoferremic hereditary spherocytosis subjects, but not in ACD patients. Increased serum concentrations of the hepcidin precursor prohepcidin were paralleled by a decreased expression of the iron exporter ferroportin in circulating monocytes of ACD patients. In the latter cells, increased amounts of the iron storage protein ferritin and a reduced activity of iron-regulatory protein indicated monocyte iron accumulation. Our data indicate that hypoferremia in ACD may result from downregulation of ferroportin expression by hepcidin and cytokines with subsequent iron retention in monocytes. Together with a diminished erythropoietin formation, the impaired iron recirculation from monocytes may be central in the pathophysiology of ACD in humans.


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