The Relevance of Iron in Erythropoietin-Stimulated Erythropoiesis

https://doi.org/10.1053/j.seminhematol.2006.08.003Get rights and content

Several clinical models have generated insight into the relationship between erythropoietin (EPO), iron, and erythropoiesis. Patients with chronic hemolytic anemias or hemochromatosis can increase erythropoiesis six- to eightfold over basal rates, whereas patients with blood loss, such as those donating autologous blood, can increase erythropoiesis only two- to fourfold over basal levels, even with pharmacologic doses of recombinant human EPO. A substantial limitation to the dose/response relationship between EPO therapy and the erythropoietic response is iron-restricted erythropoiesis, even in the presence of storage iron. Novel approaches to iron supplementation therapy when erythropoietic agents are used are indicated.

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.

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