Anaemia in patients with kidney diseases is commonly treated with erythropoietin, known as EPO for short. This treatment was introduced in the 1980s, and was a huge advance. Information about renal anaemia and its treatment with recombinant erythropoietin (EPO) is vailable from other sources: for example from Cardiff, Baxter Healthcare's Kidneywise (UK), and (more detailed) from the Kidney Transplant/Dialysis Association Patient Handbook (Boston, USA; see their home page).
This page provides information for patients about a rare complication of treatment with EPO, pure red cell aplasia, or PRCA. More detailed technical information is available for healthcare professionals or for others with adequate technical background information.
Red blood cells are made in the bone marrow to carry oxygen round the body from the lungs. Bone marrow is found in the middle of long bones like the thigh bone. EPO controls the number of red cells in blood. EPO is made in normal kidneys. If you become anaemic, more EPO should be produced, and this causes the bone marrow to make more red blood cells. Being short of oxygen for a long period has the same effect, for example because of lung disease, or living at high altitude. You can then become polycythaemic - having too many red blood cells, the opposite of anemia.
People with kidney failure do not make enough EPO. This is one of the main causes of anaemia in renal failure. Giving EPO injections usually improves the anaemia.
LEFT: Red blood cells. This photo comes from the American Red Cross website.
Pure red cell aplasia (PRCA) means failure of red cells to develop. Other blood cells (white blood cells, platelets) are produced normally, or near normally, and this is an important difference from many other blood disorders. There are a number of other possible causes of PRCA, including some virus infections and some cancers, although sometimes no reason can be found. Occasionally it is caused by antibodies to EPO.
Antibodies should normally be produced to fight infections, not to attack a normal part of the body. However in some diseases they attack something in the body - these are autoimmune diseases. Thyroid disease is an example of a common autoimmune disease, but there are many others, including a number that damage the kidney. Usually the cause is unknown, although sometimes a reaction to a drug or infection seems to be the cause.
Recently there have been a number of cases where patients receiving EPO injections have suddenly become very anaemic. The reason appears to be that these people suddenly start producing an antibody to EPO (anti-EPO antibody) which means all EPO, whether natural or artificial in origin is destroyed. If there is no EPO the bone marrow will not produce any red blood cells, causing PRCA.
A few cases of this have been described in the 80s and 90, but there seemed to be a sudden increase in the occurence of this problem betwen 1999 and 2002. These cases have mostly occured in Europe, and in patients receiving EPO as an injection under the skin (subcutaneous injection), rather than into a vein (intravenous injection). This happened particularly in patients receiving one type of EPO (epoetin alfa, Eprex).
Intensive investigations into this problem are under way. However the number of new cases occuring dropped dramatically during 2003.
We are currently researching this fairly recent phenomenon of PRCA and anti-EPO antibodies. For example:
- What triggers it?
- Why are some people affected and not others?
- Can we prevent it?
The group includes Professor Neil Turner (Renal Medicine, Edinburgh), Dr Anna Thompson (Edinburgh), Dr Iain Macdougal (Renal Medicine, London) and Dr Judith Marsh (Haematology, London).
There are 3 elements to the research:
1) Information gathering
I shall be collecting information about each case of confirmed PRCA with EPO antibodies. This information is kept in the patient case records and includes details of relevant medical history, medications, type/dose/duration of EPO treatment, blood tests and any subsequent treatment. This information is confidential initials and date of birth are recorded only to prevent duplication of results. No information will be passed on to drug companies. The results of the study may be published but individual patients will not be identified.
2) Bone marrow samples
PRCA is diagnosed by a bone marrow sample which you have probably already had. It is important to have standardised reporting of all these samples so we can compare them accurately. Dr Marsh is undertaking this at St George's Hospital, London. The bone marrow slides will be sent to St Georges and returned to the parent hospital when reported.
3) Blood samples
At present the only way to test for EPO antibodies is to send a blood sample abroad to either France, Germany or the USA. We are trying to establish a service here in the UK, both in London and Edinburgh. In order to do this we need blood samples from people who are known to have these antibodies so we can check our method is reliable. We require 10mls of blood which can be collected with routine samples. In some cases we can retrieve old samples that have been stored previously in the hospital laboratories.
Some of the funding for this research has
been provided by Ortho Biotech, one of the companies that make
EPO. However, the direction of the investigation and any results
published are not influenced by any companies, and no patient
information will be passed on to any company .
information is published from the Renal Unit at the Royal Infirmary
of Edinburgh, Scotland, UK, Renal@ed.ac.uk The authors of this page were
Anna Thompson and Neil Turner. It was first published in December 2002, and updated
Please be aware that while we have made all efforts to ensure that this information is accurate, we cannot guarantee that there are no mistakes. Also that the best management for individual patients may differ from that outlined here. Only the doctors caring for the patient will be able to advise on this.