Pure red cell aplasia (PRCA) is a rare condition that affects a very small group of patients treated with the hormone Erythropoeitin (EPO) or similar products. The first symptoms a patient may notice is that they become increasingly tired, breathless on exertion and look pale. These are symptoms of anaemia. They become gradually noticeable over days and weeks. Patients may require blood transfusions as more common treatments to improve anaemia do not work.

Prevention

There is some evidence (Macdougall et al, 2012) that most cases of PRCA are related to poor handling and storage of the drug EPO. The incidence of the disease has dropped since strict implementation of the manufacturer’s guidelines on handling and storage. For patients who self-administer EPO, it is very important to follow the manufacturer guidelines. These are provided by the patient’s clinician or nurse specialist.

Diagnosis

A first step is to get the right diagnosis. Erythropoiesis Stimulating Agents (ESA) induced PRCA is a specific type of anaemia. While kidney patients may develop anaemia for a variety of reasons, in PRCA the hormone EPO fails to increase the production of new red blood cells. Without this stimulus the blood count falls slowly. Increasing the dose of EPO has no effect. Specifically, patients develop an antibody that blocks the action of EPO.

Once the treating clinician suspects the condition, the precise diagnosis is confirmed by two tests. One is a bone marrow examination to confirm that no new red blood cells are being produced. The second is a specific blood test to identify the antibody.

Treatment

Treatment consists of:

• Blood transfusions to overcome the anaemia. These may have to be repeated.
• Discontinuation of EPO because it has become ineffective. Also further exposure to EPO might allow the antibody response to persist.
• Kidney transplantation. There are few cases of patients whose PRCA recovered following kidney transplantation. It is not clear whether the transplant process itself or the immosupressant medicines allow the recovery.
• Immunosuppressive therapy. This attempts to suppress the antibodies which are the cause of PRCA.

Pending

A Facebook group for ESA Induced Pure Red Aplasia has been established.

Red blood cells are produced in the bone marrow. This is dependent upon the hormone Erythropoeitin (EPO) which is made in the kidneys. Patients with kidney failure become anaemic largely because EPO production falls. Patients with anaemia due to kidney failure are commonly treated with synthetic versions of EPO, given by injection. Patients with PRCA develop an antibody against EPO. This means that EPO no longer works properly and the anaemia returns.

There are several different preparations of the synthetic hormone EPO used in treatment. (e.g. epoetin alfa, epoetin beta, darbepoetin alfa). There are minor structural differences between these and the naturally occurring human EPO. The reason why people exposed to EPO treatment develop antibodies is not clear. However poor storage and handling of the drug is suspected to be a risk factor.

Most cases of PRCA have occurred in patients with chronic kidney disease (CKD) who have received the drug subcutaneously (having the injection under the skin rather than into the vein or intravenously). Subcutaneous administration of drugs has been associated with a generally greater risk of immune complications than when the same drugs are given intravenously.

The PRCA Rare Disease Group (RDG) is working with international partners with the aim early identification of patients affected. A first step is to streamline the diagnostic process. The group will also try to identify potential risk factors and find new and improved treatments with the aim of empowering patients.

To do this the RDG is registering patients with this condition in the National Renal Rare Disease Registry (RaDaR).The registry will be used to find suitable participants for future research trials into identifying risk factors for the disease and evaluating the effectiveness of new treatments. If you are interested in finding out more about RaDaR or the activity of the RDG please visit the PRCA RDG page.