Approach Considerations

The initial treatment plan should include transfusions for patients who are severely anemic and have cardiorespiratory failure. Anemia is more severe in patients with pure red cell aplasia (PRCA) who have ongoing hemolysis (aplastic crises).

Medications that could cause PRCA should be discontinued.

Children with PRCA should be observed and not aggressively treated to avoid corticosteroid-related growth retardation. This caution is feasible since PRCA in children is often transient and reversible. However, transfusion should be administered if indicated.

Infections should be treated. High-dose intravenous immunoglobin therapy should be considered for parvovirus B19 infections.^[32]PRCA due to medication or infections is usually reversible within a few months, if not earlier. However, immunotherapy may be needed to reverse erythropoiesis-stimulating agent (ESA)–related PRCA.

Underlying conditions should be treated. These conditions include a thymoma, hematologic malignancies such as T-cell large granular lymphocyte leukemia,^[33]solid tumors, and systemic lupus erythematosus (SLE). Surgery or gamma irradiation of the thymus should be considered in a patient with a thymoma.

Idiopathic PRCA due to autoimmunity should be initially treated with corticosteroids.^{[1, 2, 29]}A response is expected within 4-6 weeks in about 45% of patients. Corticosteroids should be judiciously given to children to avoid growth retardation. Immunosuppressive agents have an important role. Immunosuppressive agents used in PRCA include cyclophosphamide, 6-mercaptopurine, azathioprine, and cyclosporine. Rituximab has been reported to be effective in managing PRCA.^{[34, 35, 30, 36]}Antithymic globulin (ATG) is another therapeutic option. Danazol has been helpful in some cases but is contraindicated in children. Plasmapheresis has been used to remove autoantibodies.

There are a number of reports of successful control of refractory/relapsed PRCA with sirolimus. However, multi-center and large-scale randomized controlled trials are needed to establish the efficacy of this treatment.^{[37, 38, 39, 40]}

Several patients have responded to plasmapheresis or lymphocytapheresis.^[41]

Autologous and nonmyeloablative allogeneic peripheral stem cell transplantation have been used, especially in patients whose disease is refractory to therapy.^[42]

Iron chelation should be considered in patients who have had multiple transfusions and have evidence of iron overload.

Surgical Care

Thymectomy might be indicated in patients with a thymoma. However, the procedure should not be performed in patients with a normal-sized thymus. About 30% of patients with thymomas respond to thymectomy.

Although not effective in most cases, splenectomy might be helpful in refractory cases. Splenectomy is indicated to manage pure red cell aplasia (PRCA) complicated by hypersplenism.

Consultations

Consultations with a hematologist and rheumatologist are indicated. A hematologist should be consulted for the diagnosis and management of pure red cell aplasia (PRCA). A rheumatologist should be consulted in patients with autoimmune disorders.

Activity

Activity might be limited in anemic patients.

Medication

Hoffman R, Benz EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J. Biology of Erythropoiesis, Erythroid Differentiation, and Maturation. Hematology: Basic Principles and Practice. 6th ed. Philadelphia, PA: Churchill Livingstone; 2013.
Young NS. Pure Red Cell Aplasia. In: Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri MA, eds. Williams Hematology. 9th ed. New York, NY: McGraw-Hill Education; 2016. 539-48.
Mangla A, Hamad H. Pure Red Cell Aplasia. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].
Hirokawa M. RPS19 mutations in patients with Diamond-Blackfan anemia. Br J Haematol. 2008. 142:911-20.
Morimoto K, Lin S, Sakamoto K. The functions of RPS19 and their relationship to Diamond-Blackfan anemia: a review. Mol Genet Metab. 2007 Apr. 90(4):358-62. [QxMD MEDLINE Link].
Boultwood J, Yip BH, Vuppusetty C, Pellagatti A, Wainscoat JS. Activation of the mTOR pathway by the amino acid (L)-leucine in the 5q- syndrome and other ribosomopathies. Adv Biol Regul. 2013 Jan. 53(1):8-17. [QxMD MEDLINE Link].
Boultwood J, Pellagatti A, Wainscoat JS. Haploinsufficiency of ribosomal proteins and p53 activation in anemia: Diamond-Blackfan anemia and the 5q- syndrome. Adv Biol Regul. 2012 Jan. 52(1):196-203. [QxMD MEDLINE Link].
Ellis SR, Gleizes PE. Diamond Blackfan anemia: ribosomal proteins going rogue. Semin Hematol. 2011 Apr. 48(2):89-96. [QxMD MEDLINE Link].
Garçon L, Ge J, Manjunath SH, Mills JA, Apicella M, Parikh S. Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients. Blood. 2013 Aug 8. 122(6):912-21. [QxMD MEDLINE Link].
Mirabello L, Macari ER, Jessop L, Ellis SR, Myers T, Giri N, et al. Whole-exome sequencing and functional studies identify RPS29 as a novel gene mutated in multicase Diamond-Blackfan anemia families. Blood. 2014 Jul 3. 124 (1):24-32. [QxMD MEDLINE Link]. [Full Text].
Gagne KE, Ghazvinian R, Yuan D, Zon RL, Storm K, Mazur-Popinska M, et al. Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia. Blood. 2014 Jul 17. 124 (3):437-40. [QxMD MEDLINE Link]. [Full Text].
Van Hook JW, Gill P, Cyr D, Kapur RP. Diamond-Blackfan anemia as an unusual cause of nonimmune hydrops fetalis: a case report. Reprod Med. 40:850-854. [QxMD MEDLINE Link].
Cherrick I, Karayalcin G, Lanzkowsky P. Transient erythroblastopenia of childhood. Prospective study of fifty patients. Am J Pediatr Hematol Oncol. 1994 Nov. 16(4):320-4. [QxMD MEDLINE Link].
Baker RI, Manoharan A, de Luca E, Begley CG. Pure red cell aplasia of pregnancy: a distinct clinical entity. Br J Haematol. 1993 Nov. 85(3):619-22. [QxMD MEDLINE Link].
Bierman PJ, Warkentin P, Hutchins MR, Klassen LW. Pure red cell aplasia following ABO mismatched marrow transplantation for chronic lymphocytic leukemia: response to antithymocyte globulin. Leuk Lymphoma. 1993 Jan. 9(1-2):169-71. [QxMD MEDLINE Link].
Bennett CL, Cournoyer D, Carson KR, Rossert J, Luminari S, Evens AM, et al. Long-term outcome of individuals with pure red cell aplasia and antierythropoietin antibodies in patients treated with recombinant epoetin: a follow-up report from the Research on Adverse Drug Events and Reports (RADAR) Project. Blood. 2005 Nov 15. 106(10):3343-7. [QxMD MEDLINE Link]. [Full Text].
Casadevall N. Pure red cell aplasia and anti-erythropoietin antibodies in patients treated with epoetin. Nephrol Dial Transplant. 2003 Nov. 18 Suppl 8:viii37-41. [QxMD MEDLINE Link].
Liu Z, Stoll VS, Devries PJ, Jakob CG, Xie N, Simmer RL, et al. A potent erythropoietin-mimicking human antibody interacts through a novel binding site. Blood. 2007 Oct 1. 110(7):2408-13. [QxMD MEDLINE Link].
al-Awami Y, Sears DA, Carrum G, Udden MM, Alter BP, Conlon CL. Pure red cell aplasia associated with hepatitis C infection. Am J Med Sci. 1997 Aug. 314(2):113-7. [QxMD MEDLINE Link].
Tomida S, Matsuzaki Y, Nishi M, Ikegami T, Chiba T, Abei M, et al. Severe acute hepatitis A associated with acute pure red cell aplasia. J Gastroenterol. 1996 Aug. 31(4):612-7. [QxMD MEDLINE Link].
Lee TH, Oh SJ, Hong S, Lee KB, Park H, Woo HY. Pure red cell aplasia caused by acute hepatitis a. Chonnam Med J. 2011 Apr. 47(1):51-3. [QxMD MEDLINE Link]. [Full Text].
Herbert KE, Prince HM, Westerman DA. Pure red-cell aplasia due to parvovirus B19 infection in a patient treated with alemtuzumab. Blood. 2003. 101:1654.
Ahsan N, Holman MJ, Gocke CD, Groff JA, Yang HC. Pure red cell aplasia due to parvovirus B19 infection in solid organ transplantation. Clin Transplant. 1997 Aug. 11(4):265-70. [QxMD MEDLINE Link].
Smalling R, Foote M, Molineux G, Swanson SJ, Elliott S. Drug-induced and antibody-mediated pure red cell aplasia: a review of literature and current knowledge. Biotechnol Annu Rev. 2004. 10:237-50. [QxMD MEDLINE Link].
Thompson DF, Gales MA. Drug-induced pure red cell aplasia. Pharmacotherapy. 1996 Nov-Dec. 16(6):1002-8. [QxMD MEDLINE Link].
Li G, Li ZQ, Yang QY, Yang JD. Acquired pure red cell aplasia due to treatment with clopidogrel: first case report. J Thromb Thrombolysis. 2013 Dec 3. [QxMD MEDLINE Link].
Carson KR, Evens AM, Bennett CL, Luminari S. Clinical characteristics of erythropoietin-associated pure red cell aplasia. Best Pract Res Clin Haematol. 2005. 18(3):467-72. [QxMD MEDLINE Link].
Bennett CL, Luminari S, Nissenson AR, Tallman MS, Klinge SA, McWilliams N, et al. Pure red-cell aplasia and epoetin therapy. NEJM. 2004. 351(14):1403-8. [QxMD MEDLINE Link].
Sawada K, Fujishima N, Hirokawa M. Acquired pure red cell aplasia: updated review of treatment. Br J Haematol. 2008 Aug. 142(4):505-14. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Wong S, Brown KE. Development of an improved method of detection of infectious parvovirus B19. J Clin Virol. 2006 Apr. 35(4):407-13. [QxMD MEDLINE Link].
Björkholm M. Intravenous immunoglobulin treatment in cytopenic haematological disorders. J Intern Med. 1993 Aug. 234(2):119-26. [QxMD MEDLINE Link].
Dhodapkar MV, Lust JA, Phyliky RL. T-cell large granular lymphocytic leukemia and pure red cell aplasia in a patient with type I autoimmune polyendocrinopathy: response to immunosuppressive therapy. Mayo Clin Proc. 1994 Nov. 69(11):1085-8. [QxMD MEDLINE Link].
Helbig G, Stella-Holowiecka B, Krawczyk-Kulis M, Wojnar J, Markiewicz M, Wojciechowska-Sadus M. Successful treatment of pure red cell aplasia with repeated, low doses of rituximab in two patients after ABO-incompatible allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia. Haematologica. 2005 Nov. 90 Suppl:ECR33. [QxMD MEDLINE Link].
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 Mar. 82(3):235-9. [QxMD MEDLINE Link].
Viviano KR, Webb JL. Clinical use of cyclosporine as an adjunctive therapy in the management of feline idiopathic pure red cell aplasia. J Feline Med Surg. 2011 Dec. 13(12):885-95. [QxMD MEDLINE Link].
Jiang H, Zhang H, Wang Y, Qi W, Cao Q, Xing L, et al. Sirolimus for the treatment of multi-resistant pure red cell aplasia. Br J Haematol. 2019 Mar. 184 (6):1055-1058. [QxMD MEDLINE Link]. [Full Text].
Chen Z, Liu X, Chen M, Yang C, Han B. Successful sirolimus treatment of patients with pure red cell aplasia complicated with renal insufficiency. Ann Hematol. 2020 Apr. 99 (4):737-741. [QxMD MEDLINE Link].
Long Z, Yu F, Du Y, Li H, Chen M, Zhuang J, et al. Successful treatment of refractory/relapsed acquired pure red cell aplasia with sirolimus. Ann Hematol. 2018 Nov. 97 (11):2047-2054. [QxMD MEDLINE Link].
Feng Y, Chen X, Cassady K, Zou Z, Yang S, Wang Z, et al. The Role of mTOR Inhibitors in Hematologic Disease: From Bench to Bedside. Front Oncol. 2020. 10:611690. [QxMD MEDLINE Link]. [Full Text].
Musso M, Porretto F, Crescimanno A, Polizzi V, Scalone R. Donor lymphocyte infusions for refractory pure red cell aplasia relapsing after both autologous and nonmyeloablative allogeneic peripheral stem cell transplantation. Bone Marrow Transplant. 2004 Apr. 33(7):769-71. [QxMD MEDLINE Link].
Passweg JR, Rabusin M, Musso M, Beguin Y, Cesaro S, Ehninger G, et al. Haematopoetic stem cell transplantation for refractory autoimmune cytopenia. Br J Haematol. 2004 Jun. 125(6):749-55. [QxMD MEDLINE Link].