What are the complications of erythropoietin

Red cell aplasia due to erythropoietin

Anemia is one of the well-known complications of chronic kidney disease, which can usually be traced back to a reduced production of erythropoietin. Recombinant human erythropoietin has been the standard therapy for such anemia since the mid-1980s. More than four million people around the world have now been treated with it.

Two years ago, the first report appeared on 13 French and British patients with chronic kidney disease who were being treated with erythropoietin and who developed pure red cell aplasia because of neutralizing antibodies to the drug. Further research indicated that more than 200 patients developed this complication in recent years. Most received epoetin alfa (Eprex®, Erypo®), which was marketed outside of the United States. It is suspected that the side effect is possibly caused by the galenic formulation. The incidence of red cell aplasia from these preparations is estimated to be 19 per 100,000 patient-years.

A retrospective study evaluated data from some British and all German and French patients who were being treated with erythropoietin for anemia due to chronic kidney disease and who had developed red blood cell aplasia with antibodies against erythropoietin prior to January 2003. Treatment of aplasia and outcome were assessed from 33 French, 8 German and 6 British patients. An improvement in erythrocyte aplasia was defined as an increase in the number of reticulocytes to more than 20,000 per µl without a transfusion.

The average age of the patients was 67 years (20 to 87), 70% men and 30% women. At the time of aplasia, all were treated subcutaneously with erythropoietin, most commonly epoetin alfa. On average, the aplasia developed after 11 months of treatment (7.5 to 14 months).

In 9 of the affected patients, only the erythropoietin preparation was discontinued, otherwise the aplasia was not treated. None of these patients made a full recovery. After discontinuing erythropoietin treatment, 37 patients received immunosuppressive therapy with intravenous immunoglobulins alone or in combination with glucocorticoids. Aplasia decreased in 78% (29) of these patients. Of the 6 patients who had a kidney transplant, all recovered within one month.

The healing rates for treatment with glucocorticoids, alone and combined with cyclophosphamide (Endoxan®) or ciclosporin (e.g. Sandimmun®), were between 56 and 88%. No relapse was observed after the end of immunosuppressive therapy, but no patient was re-administered with erythropoietin.