What is being tested?

This test measures the amount of erythropoietin in the blood. Erythropoietin is a hormone produced primarily by the kidneys. It is created and released into the bloodstream in response to low oxygen levels. Erythropoietin is carried to the bone marrow, where it works to stimulate stem cells to become red blood cells (RBCs). RBCs contain haemoglobin, a protein that carries oxygen throughout the body. Normal RBCs have a lifespan of about 120 days and are usually similar in size and shape.

The body has a dynamic feedback system that attempts to maintain a relatively stable number of RBCs. If there are too few produced or too many lost (through bleeding) or destroyed (haemolysis), or if the RBCs are abnormal (in shape, size or function of haemoglobin) then the patient will become anaemic and their ability to transport oxygen will diminish. Normal red blood cell production relies on the functional ability of the bone marrow, on an adequate supply of iron and nutrients such as vitamin B12 and folate and on an appropriate concentration of and response to erythropoietin.

The amount of erythropoietin released depends upon the severity of the hypoxia and the ability of the kidneys to produce it. The hormone is active for a short period of time and then eliminated from the body in the urine. 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. However, if the kidneys are damaged and/or unable to keep up with the demand for erythropoietin, or if the patient's bone marrow is unable to respond to the stimulation (such as may occur with a bone marrow disorder), then the patient may become increasingly anaemic.

If there is too much erythropoietin produced, such as may occur with some benign or malignant kidney tumours and with a variety of other cancers, too many RBCs may be produced (polycythaemia). This can lead to an increase in the volume of the blood in circulation, an increase in the blood's viscosity and to hypertension.

In one type of polycythaemia, called polycythaemia vera, the excessive production of red cells occurs independently of erythropoietin levels. In these patients the erythropoietin level may be quite low. In patients with other forms of excessive red blood cell production the erythropoietin level is high.

How is it used?

Erythropoietin is not a routine test. It is ordered primarily to help differentiate between different types of polycythaemia or anaemia and to determine whether the amount of erythropoietin being produced is appropriate for the level of anaemia present. It is usually ordered following abnormal findings on a full blood count (FBC), a group of tests that includes a RBC count and evaluation, haemoglobin and haematocrit. These tests establish the presence and severity of polycythaemia and/or anaemia and give the doctor clues as to the likely origin of the anaemia. Erythropoietin is ordered either to differentiate which type of polycythaemia is present or to help determine if an insufficiency of the hormone may be causing and/or exacerbating the anaemia.

In patients with chronic kidney disease it may be ordered at intervals to evaluate the kidneys' continued ability to produce sufficient erythropoietin. The erythropoietin test is not usually used as a monitoring tool for anaemia. This is done by following the RBC count, haemoglobin, haematocrit and reticulocyte count (a measurement of immature RBCs in the blood and an indicator of bone marrow function).

Occasionally, an erythropoietin test may be ordered to help determine if a condition that is causing an excess production of RBCs is due to an overproduction of erythropoietin.

When is it requested?

In patients with too many RBCs an erythropoietin level may be ordered during an investigation of the overproduction to see if increased erythropoietin concentrations are present. Less commonly an erythropoietin test may be ordered when a patient has anaemia that does not appear to be caused by iron deficiency, vitamin B12 or folate deficiency, haemolysis or blood loss (such as gastrointestinal bleeding). It may be ordered when the patient's RBC count, haemoglobin and haematocrit are decreased and the reticulocyte count is normal or decreased (indicating that the bone marrow has not responded to the anaemia by increasing RBC production). It is ordered when the doctor is attempting to distinguish between a condition that is suppressing bone marrow function and an insufficiency of erythropoietin. It is very useful when a patient has an excessive number of red blood cells to determine if the polycythaemia is erythropoietin dependent or independent.

In patients with chronic kidney disease erythropoietin levels may be ordered whenever a doctor suspects that kidney dysfunction could be interfering with erythropoietin production.

In patients with too many RBCs an erythropoietin level may be ordered during an investigation of the overproduction to see if increased erythropoietin concentrations are present.

What does the result mean?

If a patient has too many RBCs and erythropoietin levels are increased, then it is likely that excess erythropoietin is being produced - either by the kidneys or by other tissue in the body. If a patient has excess RBC production and erythropoietin levels are normal or low then it is likely that the polycythaemia has a cause that is independent of erythropoietin production.

If erythropoietin levels are increased and the patient is anaemic but not producing a sufficient number of new RBCs then the anaemia is likely to be related to a decrease in bone marrow function. If the patient is anaemic and erythropoietin levels are low or normal then the kidneys may not be producing an appropriate amount of the hormone.

Is there anything else I should know?

If a patient's anaemia is due to a vitamin B12, folate or iron deficiency then the anaemia may persist even when adequate amounts of erythropoietin are being created. The RBCs produced in these deficiencies may be not be normal in size, shape and/or haemoglobin content. If the patient is producing an abnormal form of haemoglobin (such as may occur with thalassemia) or has a bone marrow disorder then increased erythropoietin may not resolve the anaemia.

A synthetic form of erythropoietin (recombinant human erythropoietin or rh-EPO) has been developed to help increase RBC production in patients with chronic kidney disease and other anaemias 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 patients.

Doctors monitor red cell levels haemoglobin levels) and prescribe only the amount of erythropoietin needed to stimulate the production of red cells to avoid blood transfusions. If some patients are given higher than recommended doses they run an increased risk of developing blood clots, heart attacks, strokes and death. Also, certain cancer patients may experience a growth in tumour 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 bloodstream. This use of the drug can be dangerous, resulting in hypertension and increasing the viscosity (thickness) of the blood. Its use has been prohibited by most sports organisations including the International Association of Athletics Federations, and erythropoietin is now being tested for as part of the Olympics anti-doping programme. This test is a urine test and determines how much of the synthetic form is present.

Common questions

• 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 doctor will work with the patient to address and minimise the effects of the resulting anaemia and may treat the patient with synthetic erythropoietin.

• 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 haemoglobin - that is important in the resolution of anaemia, 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.

More information

RCPA Manual: Erythropoietin