By: Neal Shah, Co Editor-In-Chief

–

Pure Red Cell Aplasia (PRCA), also known as erythroblastopenia, is characterized by a suppression of erythrocytes in the bone marrow.  It is a peculiar oddity that the bone marrow’s progenitor cells still differentiate into white blood cells and platelets.¹  PRCA has idiopathic, viral, auto-immune, and genetic etiologies.  Diamond-Blackfan syndrome features PRCA due to defective red blood cell (RBC) production¹ resulting from genetic abnormalities in ribosomal protein production.²  Infection with the parvovirus B19 is linked to PRCA in immunocompromised patients,³ and thymomas often present in up to 15% of PRCA cases.⁴

Drug induced PRCA is often seen with administration of erythropoiesis stimulating agents (ESA) such as Aranasp® (darbepoeitin) and Procrit® (epoeitin).⁵  The administration of these exogenous peptides results in antibody formation and subsequent destruction of erythrocyte precursors.  PRCA occurs most frequently when ESAs are administered subcutaneously.⁶  Discontinuation of the ESA usually does not stop PRCA from occurring, but immunosuppressive agents are shown to slow progression.⁷  In March 2012, the FDA approved the drug Omontys® (peginesatide).⁸  This drug does not resemble typical ESA because it is not a direct erythropoietin mimetic; instead it is a pegylated dimer that directly activates erythropoesis.  It is currently indicated for the treatment of anemia due to chronic kidney disease for patients on dialysis.¹⁰

Treatment of PRCA involves discontinuation of all ESA agents and a course of corticosteroids to suppress the immune system.¹¹  Some immunosuppresants including cyclophosphamide and cyclosporine are also successful in mitigating PRCA.^12,13  Rituximab is also shown to be effective in treating PRCA.¹⁴

SOURCES:

1. Raphael Rubin, David Strayer. Rubin’s Pathology, 5^th edition. Lippincott Williams & Wilkins, Wolters Kluwer. 2008;867.
2. Diamond-Blackfan anemia. Available at: http://ghr.nlm.nih.gov/condition/diamond-blackfan-anemia. Accessed June 24, 2012.
3. Gilsanz F, Garcia Vela J, Vargas JA et al. Acquired pure red cell aplasia: a study of six cases. Ann Hematol. 1995;71(4):181—3.
4. Pure Red Cell Aplasia. Available at: http://emedicine.medscape.com/article/205695-overview#a0104asd. Accessed June 24, 2012.
5. Information on Erythropoiesis-Stimulating Agents (ESA) Epoetin alfa (marketed as Procrit, Epogen), Darbepoetin alfa (marketed as Aranesp). Available at: http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm109375.htm. Accessed June 24, 2012.
6. Erythropoiesis-stimulating agents and antibody-mediated pure red-cell aplasia: here are we now and where do we go from here? Available at: http://ndt.oxfordjournals.org/content/19/2/288.full. Accessed June 24, 2012.
7. Rossert J, Macdougall I, Casadevall N. Antibody-mediated pure red cell aplasia (PRCA) treatment and re-treatment: multiple options. Nephrol Dial Transplant. 2005;20 Suppl 4:iv23—2
8. Mikhail A. Profile of peginesatide and its potential for the treatment of anemia in adults with chronic kidney disease who are on dialysis. J Blood Med. 2012;3:25—31. Epub 2012 May 23.
9. Green JM, Leu K, Worth A et al. Peginesatide and erythropoietin stimulate similar erythropoietin receptor-mediated signal transduction and gene induction events. Exp Hematol. 2012;40(7):575—87. Epub 2012 Mar 6.
10. Omontys [package insert]. Palo Alto, CA: Affymax, Inc; 2012.
11. Sawada K, Fujishima N, Hirokawa M. Acquired pure red cell aplasia: updated review of treatment. Br J Haematol. 2008;142(4):505—14.
12. Gupta R, Ezeonyeji A, Thomas A, Scully M, Ehrenstein M, Isenberg D. A case of pure red cell aplasia and immune thrombocytopenia complicating systemic lupus erythematosus: Responseto rituximab and cyclophosphamide. Lupus. 2011;20(14):1547—1550.
13. Björkholm M. Intravenous immunoglobulin treatment in cytopenic haematological disorders. J Intern Med. 1993;234(2):119—26.
14. D’Arena G, Vigliotti ML, Dell’Olio M, Villa MR, Mantuano S, Scalzulli PR, et al. Rituximab to treat chronic lymphoproliferative disorder-associated pure red cell aplasia. Eur J Haematol. 2009;82(3):235—9.