The role of iron in erythropoiesis in the absence and presence of erythropoietin therapy.

Preoperative autologous blood donation has served as a model for blood loss anaemia. Studies in these patients, along with clinical trials of i.v. iron and recombinant human erythropoietin (rHuEPO) therapy, have furthered our understanding of the relationship between erythropoietin, iron, and erythropoiesis. With supplemental oral iron, the endogenous erythropoietic response to routine autologous blood donation and to the anaemia of chronic illness has been shown to be modest, but predictable. In more aggressive donation and more severe anaemia, the endogenous erythropoietic response is more substantial, but still predictable. Studies in patients undergoing aggressive phlebotomy whilst receiving rHuEPO demonstrate a wide variation in response to rHuEPO dose. This variability is not related to age or gender and suggests factors such as iron-restricted erythropoiesis may be responsible. Supporting evidence arises from the superior erythropoietic response observed in patients with haemochromatosis. These patients maintain very high serum iron and transferrin saturation levels. In response to serial phlebotomy these patients can mount an endogenous erythropoietin response up to five-times greater than healthy individuals. When treated with rHuEPO, patients with haemochromatosis respond with much greater RBC expansion volumes than patients receiving rHuEPO and iron supplementation. Studies show no difference in the degree of endogenously stimulated erythropoiesis between patients with measurable iron stores and those without. However, when treated with rHuEPO, increased erythropoiesis has been observed in patients with measurable iron stores compared with those without. This suggests that, while oral iron supplementation may be sufficient to keep pace with endogenously stimulated erythropoiesis, it may not be adequate to prevent iron-restricted erythropoiesis during rHuEPO therapy. Some studies have suggested that i.v iron may prevent iron-restricted erythropoiesis during rHuEPO therapy although further research is needed. The availability of better tolerated i.v. iron preparations provides an ideal opportunity to study the value of iron therapy in patients with acute blood loss, particularly those undergoing rHuEPO therapy.