Erythropoietin (EPO)

EPO is not a routine test. It is requested mainly to help distinguish between different types of polycythaemia or anaemia and to find out whether the amount of EPO being produced is appropriate for the level of anaemia present. It is usually requested following abnormal findings on a full blood count (FBC), These tests establish the presence and severity of polycythaemia and/​or anaemia and give the doctor clues as to the likely origin.

In patients with chronic kidney disease it may be used at intervals to test the kidneys’ continued ability to produce sufficient EPO. The EPO 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 EPO test may be used to help find out if a disease that is causing an excess production of RBCs is due to an overproduction of EPO.

An EPO test may be requested 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 used 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 used when the doctor is attempting to distinguish between a disease that is suppressing bone marrow function and an inadequate amount of EPO. It is very useful when a patient has an excessive number of red blood cells to determine if the polycythaemia is EPO dependent or independent.

In patients with chronic kidney disease EPO levels may be used whenever a doctor suspects that kidney disease could be interfering with EPO production.

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

What causes high levels of EPO?

High levels of EPO can cause high levels of red blood cells. This is called polycythaemia.

The classification of polycythaemia is subdivided into primary polycythaemia (which is caused by a genetic mutation causing inappropriate production of red blood cells) and secondary polycythaemia.

Primary polycythaemia causes low EPO levels because your kidneys sense that you have enough red blood cells, so they don’t produce as much EPO.

Secondary polycythaemia is due to chronic hypoxia which results in a compensatory increase in red blood cell production. Some causes of secondary polycythaemia include:

Congestive heart failure
Chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema
Interstitial lung disease
Smoking
Obstructive sleep apnoea
High altitude

In rare cases, certain tumours can also cause your kidneys to release inappropriately excessive EPO. Anaemia may not result from kidney disease and still cause high EPO levels. Anaemia happens when you don’t have enough red blood cells or your red blood cells don’t work as they should. It can cause high levels of EPO because your kidneys sense that you don’t have enough red blood cells, so they release extra EPO. This is a normal and appropriately high level of EPO.

What causes low levels of EPO?

Chronic kidney disease (CKD) is the most common cause of low EPO levels. Damaged kidneys can’t produce as much EPO, leading to low levels. CKD and low EPO levels can lead to anaemia. Primary polycythaemia causes low EPO levels because your kidneys sense that you have enough red blood cells, so they don’t produce as much EPO.

As a synthetic performance-enhancing drug, EPO has been banned since the early 1990s. 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 and it 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.

Not directly. If an insufficiency is due to a temporary kidney condition then it may improve as the condition get better. 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 affects of the resulting anaemia and may treat the patient with synthetic erythropoietin.

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.