The biology and clinical applications of recombinant erythropoietin

Abstract

Erythropoietin (EPO) is one of the few hematopoietic growth factors that behaves like a hormone. Produced primarily in the kidneys in adults, and to a small extent in the liver, EPO acts to promote the proliferation and maintain the survival of erythroid progenitor cells. To act as a mitogen and be able to achieve the plasma concentration necessary to trigger dormant primitive erythroid progenitors into cell cycle, EPO production must be both constitutive and inducible. Erythropoietin production is regulated at the level of its gene, and hypoxia is the only physiologic stimulus for upregulating its production. Therefore, under normal circumstances, the plasma EPO level reflects the status of EPO production. However, since a variety of disorders, as well as certain drugs, can influence EPO production, its plasma level cannot simply be used as a surrogate measure of tissue oxygenation. However, because of the strong inverse correlation between hemoglobin or hematocrit level and plasma EPO, the plasma EPO level can be used to determine whether EPO production is appropriate to the severity of an anemia. An inappropriately low plasma EPO level suggests hormone deprivation. In this situation, if bone marrow function is otherwise normal, there are no other correctable causes for anemia, and the patient is symptomatic or will require blood transfusions, therapy with recombinant EPO (epoetin) should be considered.