One of the rare but serious side effects of recombinant erythropoietin therapy is the possibility of pure red cell aplasia, an autoimmune condition in which antibodies against erythropoietin result in T-cell-mediated destruction of erythroid precursors. It may be recognized by an escalating EPO requirement and need for transfusions despite adequate iron stores. It has been reported much more frequently in Europe (with a formulation called Eprex, not used in the U.S.) and is thought to be at least partially due to the practice of subcutaneous administration there rather than in the U.S. where intravenous EPO therapy, for reasons of reimbursement, is the rule. The diagnosis of pure red cell aplasia requires a bone marrow biopsy which demonstrates a lack of erythroid precursors with a preservation of megakaryocyte and myeloblast lineages; in a recent case at our hospital one of the major manufacturers of EPO products was contacted and performed an assay looking for EPO-specific antibodies. Being a rare condition, there is limited data on how best to treat acquired pure red cell aplasia, but standard practice currently consists of withdrawing EPO and giving a course of immunosuppressive therapy with Cytoxan and prednisone.
There are other causes of pure red cell aplasia: a genetic condition (Diamond-Blackfan Syndrome) as well as other forms of acquired disease, which include leukemia/lymphoma, viral infection (e.g., hepatitis C, HIV, parvovirus B19), or drugs. It may also be a prodrome to a full-blown myelodysplastic syndrome.