Erythropoietin (EPO) is a glycoprotein hormone consisting of 165 amino acids, with four complex carbohydrate chains attached to the peptide at four linkage 1 sites. It has a molecular weight of 36,000 daltons, 40% of this attributed to the carbohydrate chains. EPO is the primary regulator of erythropoiesis, stimulating the proliferation and differentiation of erythroid precursor cells in bone marrow. In mammals, the fetal liver produces nearly all of the hormone; in adults, hepatic production drops to under 10% and renal secretion accounts for over 90%. The production site is believed to be the proximal renal tubular cells or the peritubular capillary endothelial cells of the renal cortex and outer medulla. The clearance of circulating EPO has not been fully explained, but it is accomplished, in small part, by urinary excretion, and possibly also by hepatic elimination and by uptake into target cells in bone marrow.
EPO adjusts red blood cell production to meet the tissue oxygen demand. It exerts its effect in a complex feedback system, in which renal secretion of the hormone is controlled by an oxygen sensor in the kidney that responds to the partial pressure of oxygen in blood. Under conditions of increased peripheral oxygen, EPO levels diminish. This is seen after correction of hypoxia in healthy subjects (as in descent from a high elevation) and after hypertransfusion.
Anemias may be divided into two categories with respect to EPO levels in blood: those that are primary to EPO evels and those that are secondary. Primary anemias are characterized by an increase of EPO in the blood to attempt to restore red blood cell production levels to normal. Examples of anemias in which EPO levels are elevated include iron deficiency anemia, reduction of blood flow to the kidney (as in blood loss) and hemoglobinopathies with increased affinity of hemoglobin for oxygen. The EPO production rate is seen to increase exponentially with the decrease in available oxygen and with falling hematocrit in nonrenal anemias; in the latter, EPO levels 1,000 times normal have been reported.
Anemia can be secondary to inflammation, rheumatoid arthritis, neoplasm, and chronic renal disease. The "secondary anemias" may, however, be at least partly attributable to underproduction of EPO.
A failure to produce sufficient EPO accounts for the moderate to severe anemias observed in end-stage renal disease. Decreased EPO production is attributed to destruction of renal production sites; the renal oxygen sensor may also be affected. Levels of the hormone slightly exceed the reference range at most, and are inadequate to counter the blood loss due to dialysis, shortened red blood cell life, iron and folate deficiency, impaired iron transfer to erythyroid progenitor cells, and other challenges faced by such patients. Anephric patients demonstrate especially low EPO levels. A few patients with chronic kidney failure, however, exhibit normal hematocrits or less serious anemia, and elevated EPO. Some of these patients have cystic kidneys or viral hepatitis; in the latter, increased EPO may have resulted from enhanced hepatic production.
Overproduction of red blood cells is called polycythemia. Polycythemias may also be divided into two categories depending on whether the condition is primary or secondary to EPO levels. In polycythemia vera, EPO levels are diminished, and erythropoiesis is primary to and independent of stimulation by EPO. Variation in EPO values can be as much as tenfold for different patients with the same hematocrit.
Certain other conditions may be characterized by the loss of feedback control of oxygen concentration over EPO production, causing an increase in EPO 3 levels. These include renal cell carcinomas, in which 2 percent of patients demonstrate erythrocytosis, and some benign renal lesions, such as single or multiple renal cysts, renal artery stenosis and microvascular abnormalities. In addition, approximately 10 percent of renal transplant patients develop erythrocytosis, sometimes from autologous diseased kidney.
Secondary polycythemia is characterized by elevated EPO levels which lead to increased red blood cell mass. This condition may result from a variety of factors, including defective hemoglobin, smoking, pulmonary fibrosis, cardiac disease, tumors, and kidney stones.
When assaying EPO for the differential diagnosis of polycythemias, the possible overlap of values for secondary erythrocytosis or for polycythemia vera with those in the reference range must be considered.
SI units Conversion Calculator. Convert Erythropoietin (EPO) level to mIU/mL, IU/L. Clinical laboratory units online conversion from conventional or traditional units to Si units. Table of conversion factors for Erythropoietin (EPO) unit conversion to mIU/mL, IU/L.