Clinical Efficacy and Safety of Erythroid Stimulating Agents in Sickle Cell Disease

Abstract ³²¹⁸

Endogenous production of erythropoietin (epo) can be decreased due to renal injury as well as by the decreased oxygen affinity of sickle hemoglobin in sickle cell disease (SCD). Erythroid stimulating agents (ESAs) are used when the endogenous production of epo is compromised and there is evidence that they may augment HbF production. However, there are potential adverse effects when using ESAs in SCD, possibly related to increased dense reticulocyte production, platelet activation, or other mechanisms. We present data on patients with SCD initiated on ESA therapy between January 2003 and January 2011. A total of 26 patients were initiated on ESA therapy during this period and eight are excluded from our analysis due to concomitant initiation of hydroxyurea. Of the 18 patients, all have HbSS disease and 14 received recombinant erythropoietin (median dose 40,000 units weekly) and four received darbopoietin (median dose 200mcg every two weeks). The median age was 44 years and eight of the 18 patients had been on a stable dose of HU (median dose 10mg/kg) prior to initiation of the ESA. Laboratory data was collected from a baseline clinical visit (defined as greater than four weeks from a vaso-occlusive pain episode or three weeks from a red blood cell transfusion) prior to starting the ESA and at one year after ESA therapy. Despite patients having a lower GFR after a year of follow up, hemoglobin values were improved and a significant proportion of patients were able to be transfusion-free. Although the increase in HbF was not statistically significant, a significant decrease in the LDH was observed. After one year of ESA therapy, there was no increased frequency of pain crises requiring medical attention or thrombotic events including stroke and the systolic and diastolic blood pressures were unchanged. Five of the patients had a prior seizure disorder and only one of the five patients developed a seizure in the year after initiating ESA therapy which was attributed to noncompliance with anti-epileptic therapy. Although limited by its retrospective nature, this study represents the largest observational cohort of SCD patients receiving ESA therapy thus far and suggests that ESA therapy may be effective in raising the hemoglobin and decreasing transfusion requirements without significant additional toxicity.