22439 Erythropoietin

​ESF, EPO​

As an aid in the diagnosis of anemia’s and polycythemias. With the advent of the administration of recombinant erythropoietin as a biologic therapy to increase red blood cell mass, an erythropoietin assay may be used also to aid in the prediction and monitoring of response to recombinant erythropoietin (rhEPO) treatment of anemia.

Separate serum from the blood within 60 minutes of venipuncture. Morning values are higher than afternoon values because of diurnal rhythm of secretion. For optimal results in serial patient monitoring, all specimens should be collected at the same time of day.

HAMA and other heterophilic antibodies in human serum can react with the antibodies included in the assay components causing interference with immunoassay. Grossly hemolyzed specimens give erroneous results.

Erythropoietin (EPO) is a glycoprotein hormone primarily produced by kidneys and regulates red cell production by bone marrow (erythropoiesis). In healthy persons there is inverse correlation between serum EPO and hematocrit; an exponential increase in EPO occurs as hematocrit decreases. Under conditions of hypoxia, the level of EPO in the circulation increases, leading to increased production of red blood cells. EPO levels in anemia are determined by the degree of anemia and not by specific effect of underlying illness on the production of EPO.
Presence of EPO level in the blood can indicate bone marrow disorders, (such as polycythemia or increased red blood cell production), kidney disease or erythropoietin abuse (Erythropoietin has been misused as a performance-enhancing drug by some athletes). Primary polycythemia (polycythemia vera) is a neoplastic (clonal) blood disorder characterized by autonomous production of hematopoietic cells. Increased erythrocytes result in compensatory suppression of EPO levels.
Various types of secondary polycythemias are associated with the production of elevated levels of EPO. Secondary polycythemias (e.g., high-altitude living and pulmonary disease) are characterized by hypoxia and a compensatory increase in red cell mass. EPO production is increased in an attempt to increase the delivery of oxygen by increasing the number of oxygen-carrying RBCs. In other instances, elevated EPO levels are the result of production by neoplastic cells. Some tumors secrete EPO or EPO-like proteins; examples include tumors of the kidney, liver, lung, and brain.
Abnormal EPO levels also may be seen in renal failure. Chronic renal failure may result in decreased renal EPO production and, subsequently, anemia.

EPO results should be interpreted in light of the total clinical presentation of the patient, including: symptoms, clinical history, data from additional tests, and other appropriate information. Polycythemia vera is unlikely when erythropoietin (EPO) levels are elevated and polycythemia vera is likely when EPO levels are suppressed. Erythropoietin (EPO) levels alone cannot reliably distinguish between primary and secondary polycythemia; EPO levels are within normal limits in some patients with primary polycythemia.

Lower EPO levels than expected have been seen with anemia’s associated with the following conditions: rheumatoid arthritis, acquired immunodeficiency syndrome, cancer, and ulcerative colitis, sickle cell disease, and in premature neonates. Patients with hypergammaglobulinemia associated with multiple myeloma or Waldenstrom's disease have impaired production of erythropoietin in relation to hemoglobin concentration. This has been linked to increased plasma viscosity.

Patients, who have either a poor or no erythropoietic response to EPO therapy, but have high-normal or high EPO levels, may have additional, unrecognized cause(s) for their anemia. If no contributing factors can be identified, the possibility that the patient may have developed EPO-antibodies should be considered. This can be a serious clinical situation that can result in red cell aplasia.

This assay cannot distinguish between endogenous and exogenous EPO. There are no specific assays for measuring recombinant EPO compounds.