The Relevance of Iron in Erythropoietin-Stimulated Erythropoiesis
Section snippets
Iron-Restricted Erythropoiesis
Erythropoiesis in response to aggressive autologous phlebotomy via endogenous EPO has been estimated to increase up to threefold.16, 26 No apparent relationship exists between basal iron stores and this magnitude of erythropoiesis, suggesting that under conditions of moderate erythropoiesis, serum iron and transferrin saturation for erythron requirements are adequately maintained by storage iron.13, 14, 15, 16 Oral iron supplementation was found to be of benefit,12, 13, 27 whereas intravenous
Iron Therapy
The success of EPO therapy in correcting the anemia of chronic renal failure has led to substantial clinical experience in iron therapy and erythropoiesis in this setting.31, 32 Hyporesponsiveness to EPO therapy is a common phenomenon33, 34 due to a variety of comorbid conditions, particularly aluminum toxicity and iron deficiency.
Anemic patients undergoing dialysis may show suboptimal response to oral iron therapy for several reasons. During EPO therapy, absorption of iron increases up to
Laboratory Evaluation
The diagnosis of iron deficiency is traditionally based on a combination of parameters, including iron metabolism and hematological indices. Technical and biologic issues limit the usefulness of these assays in the clinical setting,49, 50, 51 and the value of iron, transferrin, and transferrin saturation is limited to uncomplicated iron deficiency. Transferrin saturation falls below 16% only when iron stores are exhausted, in contrast to EPO therapy-induced erythropoiesis, in which iron
Conclusion
Under conditions of normal iron stores, the maximal erythropoietic response to anemia, with or without pharmacologic doses of erythropoietic agents, is a 350% or 200% increase, respectively, over basal erythropoiesis.
This two- to fourfold increase is limited by functional iron deficiency. The availability of safer intravenous iron preparations allows an opportunity to study their value in optimizing the erythropoietic response to anemia.
References (75)
Erythropoiesis, erythropoietin, and iron
Blood
(1982)The metabolism of hemoglobin and bile pigment in hemolytic disease
Am J Med
(1955)- et al.
Erythropoietin, iron, and erythropoiesis
Blood
(2000) The erythropoietin-hematocrit relationship in normal and polycythemic man: Implications of marrow regulation
Blood
(1968)- et al.
Red blood cell regeneration induced by subcutaneous recombinant erythropoietin: Iron-deficient erythropoiesis in iron-replete subjects
Blood
(1993) - et al.
Perisurgical erythropoietin application in anemic patients with colorectal cancer: A double-blind randomized study
Surgery
(1996) - et al.
Reduction in recombinant human erythropoietin doses by the use of chronic intravenous iron supplementation
Am J Kidney Dis
(1995) - et al.
Erythropoietin hyporesponsiveness: From iron deficiency to iron overload
Kidney Int
(1999) - et al.
Efficacy of oral iron therapy in patients receiving recombinant human erythropoietin
Am J Kidney Dis
(1995) - et al.
Intravenous iron supplementation for the treatment of the anemia of moderate to severe chronic renal failure patients not receiving dialysis
Am J Kidney Dis
(1996)
Regulation of cellular iron metabolism by erythropoietin: Activation of iron-regulatory protein and upregulation of transferrin receptor expression in erythroid cells
Blood
Iron overload in renal failure patients: Changes since the introduction of erythropoietin therapy
Kidney Int
Disorders of iron metabolismDiagnostic methods
Clin Haematol
Serum ferritin as a measure of iron stores in normal subjects
Am J Clin Nutr
Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency
Blood
Prediction of response to erythropoietin treatment in chronic anemia of cancer
Blood
Recombinant human erythropoietin in the anemia associated with multiple myeloma or non-Hodgkin’s lymphoma: Dose finding and identification of predictors of response
Blood
Prediction of response to recombinant human erythropoietin (r-HuEPO/epoetin-alpha) therapy in cancer patients
Blood
Effects of recombinant human erythropoietin combined with granulocyte/macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome
Blood
Multicenter study of recombinant human erythropoietin in correction of anemia in patients with rheumatoid arthritis
Am J Med
Recombinant human erythropoietin in transfusion-dependent anemic patients with multiple myeloma and non-Hodgkin’s lymphoma—A randomized multicenter study
Blood
Control of marrow production by the level of iron supply
J Clin Invest
Treatment of haemochromatosis by energetic phlebotomy; one patient’s response to the letting of 55 litres of blood in 11 months
Br J Haematol
Rate of regeneration after blood loss
AMA Arch Intern Med
Perspectives in iron metabolism
N Engl J Med
Limitations of the erythropoietic response to serial phlebotomy: Implications for autologous blood donor programs
J Lab Clin Med
Effect of repeated whole blood donations on serum immunoreactive erythropoietin levels in autologous donors
JAMA
Preoperative red cell production in patients undergoing weekly autologous blood donation
Transfusion
Efficacy of oral iron supplementation is not enhanced by additional intravenous iron during autologous blood donation
Transfusion
Oral or intravenous iron as an adjunct to autologous blood donation in elective surgery: A randomized, controlled study
Transfusion
Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy
N Engl J Med
Preoperative red blood cell production in patients undergoing aggressive autologous blood phlebotomy with and without erythropoietin therapy
Transfusion
A phase III trial of recombinant human erythropoietin therapy in nonanemic orthopedic patients subjected to aggressive removal of blood for autologous use: dose, response, toxicity, efficacy
Transfusion
A standardized method for calculating blood loss
Transfusion
Red blood cell mass in autologous and homologous blood unitsImplications for risk/benefit assessment for autologous blood crossover and directed blood transfusion
Transfusion
Erythropoietin response to anaemia is not altered by surgery or recombinant human erythropoietin therapy
Br J Haematol
Cited by (7)
State of the iron: How to diagnose and efficiently treat iron deficiency anemia in inflammatory bowel disease
2013, Journal of Crohn's and ColitisCitation Excerpt :Thus, in the presence of inflammation, functional ID should be defined by low TfS (< 20%) and normal ferritin concentrations (> 100 ng/mL), whereas low TfS (< 20%) and intermediate ferritin values (30–100 ng/mL) suggest absolute ID.16 Functional ID may also occur in response to the therapeutic use of erythopoiesis stimulating agents, which place a significant demand on iron stores that may surpass the iron-release capacity of the RES.37 ID can also be defined by a ferritin index > 3.2 (> 2.0 if CRP > 5 mg/L).
Role of iron replacement in the management of preoperative anemia
2012, Transfusion Alternatives in Transfusion MedicineLaboratory diagnosis of iron deficiency
2012, Transfusion Alternatives in Transfusion MedicineDisorders of iron metabolism. Part II: Iron deficiency and iron overload
2011, Journal of Clinical PathologyAn update on iron physiology
2009, World Journal of Gastroenterology