When you have anemia that your healthcare practitioner suspects may be caused by decreased red blood cell production; when you are producing too many red blood cells
A blood sample drawn from a vein in your arm
Erythropoietin (EPO) is a hormone produced primarily by the kidneys. It plays a key role in the production of red blood cells (RBCs), which carry oxygen from the lungs to the rest of the body. This test measures the amount of erythropoietin in the blood.
Erythropoietin is produced and released into the blood by the kidneys in response to low blood oxygen levels (hypoxemia). EPO is carried to the bone marrow, where it stimulates production of red blood cells. The hormone is active for a short period of time and then eliminated from the body in the urine.
The amount of erythropoietin released depends upon how low the oxygen level is and the ability of the kidneys to produce erythropoietin. Increased production and release of erythropoietin continues to occur until oxygen levels in the blood rise to normal or near normal concentrations, then production falls. The body uses this dynamic feedback system to help maintain sufficient oxygen levels and a relatively stable number of RBCs in the blood.
However, if a person's kidneys are damaged and do not produce sufficient erythropoietin, then too few RBCs are produced and the person typically becomes anemic. Similarly, if a person's bone marrow is unable to respond to the stimulation from EPO, then the person may become anemic. This can occur with some bone marrow disorders or with chronic diseases, such as rheumatoid arthritis. (Read Anemia of Chronic Diseases to learn more.)
Individuals who have conditions that affect the amount of oxygen they breathe in, such as lung diseases, may produce more EPO to try to compensate for the low oxygen level. People who live at high altitudes may also have higher levels of EPO and so do chronic tobacco smokers.
If too much erythropoietin is produced, as occurs with some benign or malignant kidney tumors and with a variety of other cancers, too many RBCs may be produced (polycythemia or erythrocytosis). This can lead to an increase in the blood's thickness (viscosity) and sometimes to high blood pressure (hypertension), blood clots (thrombosis), heart attack, or stroke. Rarely, polycythemia is caused by a bone marrow disorder called polycythemia vera, not by increased erythropoietin.
How is it used?
An erythropoietin (EPO) test is used primarily to help diagnose the cause of anemia. It can help identify candidates for erythropoietin replacement therapy (e.g., people with chronic kidney disease). Sometimes it is used to help diagnose the cause of too many red blood cells (polycythemia or erythrocytosis) or as part of an evaluation of a bone marrow disorder.
An EPO test is usually ordered in follow up to abnormal findings on a complete blood count (CBC), such as a low red blood cell (RBC) count and low hemoglobin and hematocrit. These tests establish the presence and severity of anemia and give the healthcare practitioner clues as to the likely cause of the anemia. Erythropoietin testing is ordered to help determine if low EPO may be causing and/or worsening the anemia.
In people with chronic kidney disease, the test may be ordered to evaluate the kidneys' continued ability to produce sufficient erythropoietin. If the erythropoietin level is low, erythropoietin replacement therapy may help increase red cell production in the bone marrow.
Occasionally, an erythropoietin test may be ordered in follow up to CBC results that show an increased number of RBCs, to help determine whether the excess production of RBCs (polycythemia or erythrocytosis) is due to an overproduction of erythropoietin or some other cause (e.g., JAK2 mutation).
When is it ordered?
An erythropoietin (EPO) test may be ordered when a person has anemia that does not appear to be caused by iron deficiency, vitamin B12 or folate deficiency, decreased lifespan of red blood cells (RBCs; hemolysis), or by excessive bleeding. It may be ordered when the RBC count, hemoglobin, and hematocrit are decreased and the reticulocyte count is inappropriately normal or decreased.
If someone has chronic kidney disease, erythropoietin levels may be ordered when the healthcare practitioner suspects that kidney dysfunction could be associated with a decrease in erythropoietin production.
An EPO test may be ordered when a complete blood count reveals that a person has an increased number of RBCs and a high hematocrit and hemoglobin.
What does the test result mean?
If a person is anemic and erythropoietin levels are low or normal, then the kidneys may not be producing an appropriate amount of the hormone.
If a person has too many red blood cells (RBCs) and erythropoietin levels are increased, then it is likely that excess erythropoietin is being produced – either by the kidneys or by other tissues in the body. This condition is called secondary polycythemia.
If there is excess RBC production and erythropoietin levels are normal or low, then it is likely that the polycythemia has a cause that is independent of erythropoietin production. This condition is called primary polycythemia.
Condition present EPO level Example(s) of possible cause(s) Anemia (low RBCs, hemoglobin and hematocrit) Low or normal Severe kidney disease Anemia High Bone marrow disorder (e.g., myelodysplastic syndrome) Polycythemia (high RBCs, hemoglobin and hematocrit) High EPO-producing kidney tumor or other tissue (secondary polycythemia) Polycythemia Normal or low Polycythemia vera (primary polycythemia)
Is there anything else I should know?
If anemia is due to a vitamin B12, folate, or iron deficiency, then the anemia may persist even when adequate amounts of erythropoietin are being produced. The red blood cells (RBCs) produced in these deficiencies may not be normal in size, shape, and/or hemoglobin content.
A synthetic form of erythropoietin (recombinant human erythropoietin or rh-EPO) has been developed to help increase RBC production in people with chronic kidney disease and other anemias related to bone marrow suppression and/or failure, such as that due to radiation or chemotherapy treatment for cancer. The drug treatment, which is given intravenously or by subcutaneous injection, is expensive and its stimulation of the bone marrow lasts only a few hours. The synthetic hormone's use has been promising, helping to decrease the need for blood transfusions and improving the quality life for many affected people.
In March 2007, however, the U.S. Food and Drug Administration (FDA) issued stronger safety warnings with regard to erythropoiesis-stimulating agents (ESAs). The public health advisory included revised product labeling and recommendations to monitor the health of those on ESAs, especially people with cancer or kidney disease. The safety information recommends that healthcare practitioners monitor red cell levels (hemoglobin levels) and prescribe only the amount of ESA needed to stimulate the production of red cells to avoid blood transfusions. If some people are given higher than recommended doses, they run an increased risk of developing blood clots, heart attacks, strokes, and death. Also, certain people with cancer may experience a growth in tumor size.
The same synthetic erythropoietin is also being used by some athletes as a form of "blood doping." Those who use it are trying to increase their endurance and oxygen capacity by increasing the number of RBCs in their blood. This use of the drug can be dangerous, resulting in hypertension and increasing the viscosity of the blood. Its use has been prohibited by most sports organizations, including the International Association of Athletics Federations, and erythropoietin is now being tested for as part of the Olympics anti-doping program. Read Drug Abuse Testing to learn more.
Can adequate erythropoietin production in the kidney be restored?
Not directly. If an insufficiency is due to a temporary kidney condition, then it may resolve as the condition resolves. In many cases, however, the decreased erythropoietin production is due to chronic kidney disease and will not get better over time. When there is a known insufficiency, the healthcare practitioner will work with the person to address and minimize the effects of the resulting anemia and may treat the person with synthetic erythropoietin (i.e., erythropoietin replacement therapy).
Why isn't erythropoietin measured to monitor erythropoietin drug therapy?
It is not used because it is the effect on the bone marrow – reflected by increased RBC and reticulocyte production and increasing hemoglobin – that is important in the resolution of anemia, not the concentration of erythropoietin in the blood. The amount needed will vary from person to person depending on their condition and the responsiveness of their bone marrow.
On This Site
Elsewhere On The Web
American Society of Hematology: Anemia
American Society of Hematology: The Story of Erythropoietin
National Kidney Foundation: Anemia and Chronic Kidney Disease
National Institute of Diabetes and Digestive and Kidney Diseases: Anemia in Kidney Disease