Anti-erythropoietin and anti-thrombopoietin antibodies induced after administration of recombinant human erythropoietin

Recombinant human erythropoietin (rhEPO) has been successfully used for correcting renal anemia. However, recent studies have raised some concerns about the safety of rhEPO treatment due to its immunogenic side effect - pure red cell aplasia (PRCA). We now report a case of development of anti-EPO neutralizing antibodies (Abs) implicated in thrombocytopenia as well as erythrocytopenia. A 35-year-old man had a history of administering rhEPO (epoetin alfa, epoetin beta and darbepoetin alfa) for 2 years to treat renal anemia. The hematological parameters were collected. Anti-EPO, anti-platelet, and anti-thrombopoietin (TPO) Ab assays were performed to test the presence of autoreactive Abs. After performing antibody assays due to severe resistance to rhEPO treatment, a high titer of anti-EPO neutralizing Abs was detected. However, unexpectedly, this patient also showed thrombocytopenia rather than PRCA. We investigated the cause of the marked thrombocytopenia and found anti-TPO Abs in patient serum. To our best knowledge, this is the first report of the development of anti-TPO Abs during rhEPO treatment for anemia.

►We found a patient with erythrocytopenia and thrombocytopenia under EPO therapy. ►Cause of erythrocytopenia was well explained by anti-EPO antibodies in patient serum. ►We demonstrated that a portion of EPO-induced antibodies were also reactive with TPO. ►Thrombocytopenia was possibly mediated by anti-TPO antibodies in serum. ►We identified for the first time anti-TPO antibodies from the EPO-treated patient.