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Erythropoietin is the principal factor controlling red cell
production. It acts on erythroid progenitor cells in thebone marrow (CFU-E,
BFU-E) and is produced primarily by peritubular interstitial cells of the
kidney. Its synthesis is stimulated by decreased oxygen delivery; the oxygen
sensor is a heme protein. Extra.renal production occurs in the liver and
in bone marrow macrophages. It was originally purified from urine of patients
with aplastic anemia and identified as an acidic glycoprotein consisting
of 166 amino acids with a molecular weight of 34 kD.
Treatment of anemia with recombinant human EPO was initially done in patients with end.stage renal disease, a disorder characterized by reduced EPO serum levels. In additional studies it was documented that EPO may be effective in patients with severe anemia with normal renal function, e.g. in the treatment of anemia associated with multiple myeloma, neoplastic bone marrow infiltration, in AIDS patients treaed with zidovudine (AZT), in chronic rheumatoid arthritis, in correcting chemiotherapy-induced anemia or anemia associated with cancer. These patients were shown to have an inappropriately Iow EPO serum level as compared to patients with a comparable degree of anemia caused by iron deficiecy. However, in patients with dyserythropoiesis (e.g. myelodysplastic syndromes), EPO therapy was beneficial only in a very small number of patients Another possible application of EPO is the increased preoperative collection of autologous blood before elective surgery and the perioperative management of Jehovah's Witnesses: Treatment with EPO increase preoperative Hb levels to a point making it possible to compensate for operative blood loss. No major side effects were seen during EPO therapy in patients with normal renal function. In patients with end-stage renal disease, however, EPO therapy was sometimes associated with hypertension, strokes, seizures and increased blood viscosity. In patients with preexisting iron overload, iron stores were decreased by EPO therapy. |