The Relevance of Iron in Erythropoietin-Stimulated Erythropoiesis

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.