Pure red cell aplasia and anti-erythropoietin antibodies in patients on hemodialysis: a report of two cases and a literature review / Aplasia pura de células vermelhas e anticorpo antieritropoietina em pacientes de hemodiálise: relato de dois casos e revisão da literatura

ABSTRACT Introduction: Anemia is a frequent multifactorial complication of CKD seen in patients on dialysis derived mainly from impaired erythropoietin (EPO) production. A less common cause of anemia in individuals with CKD is pure red cell aplasia (PRCA) secondary to the production of anti-EPO antibodies. Objective: This paper aimed two describe two cases of PRCA secondary to the production of anti-EPO antibodies including choice of treatment, patient progression, and a literature review. Materials: This study included the cases of two patients with CKD on hemodialysis with severe anemia in need of specific investigation and management. Results: Patient 1 with CKD secondary to hypertension treated with EPO for 7 months showed persistent decreases in hemoglobin (Hb) levels despite the subcutaneous administration of increasing doses of EPO; the patient required recurring blood transfusions. Workup and imaging tests were negative for the main causes of anemia in individuals with CKD on dialysis. Patient 2 with CKD secondary to adult polycystic kidney disease had been taking EPO for 2 years. The patient developed severe abrupt anemia the month he was started on HD, and required recurring transfusions to treat the symptoms of anemia. Workup and imaging findings were inconclusive. Specific laboratory tests confirmed the patients had anti-EPO antibodies. After six months of immunosuppressant therapy (corticosteroids + cyclosporine) the patients were stable with Hb > 9.0 g/dl. Conclusion: PRCA is a rare condition among patients on dialysis treated with rhEPO and should be considered as a possible cause of refractory anemia. Treating patients with PRCA may be challenging, since the specific management and diagnostic procedures needed in this condition are not always readily available.

RESUMO Introdução: Anemia é complicação frequente da Doença Renal Crônica (DRC) em pacientes dialíticos. Apresenta caráter multifatorial principalmente pela insuficiente produção de eritropoietina (EPO). Situação rara causadora de anemia na DRC é Aplasia Pura de Células Vermelhas (APCV), em decorrência da produção de anticorpos anti-EPO. Objetivo: Descrever 2 casos de APCV com formação de anticorpos anti-EPO, sua abordagem clínica, evolução e revisão de literatura. Métodos: Dois pacientes em hemodiálise que desenvolveram anemia grave, necessitando investigação e manejo específico. Resultados: Paciente nº 1: feminina, 75 anos, DRC secundária à hipertensão arterial. Após 7 meses com EPO desenvolveu queda persistente em valores de hemoglobina (Hb) mesmo com incremento em doses EPO SC, necessitando transfusões de sangue recorrentes. Extensa investigação laboratorial e de imagem resultou negativa para principais causas de anemia. Paciente nº 2: masculino, 66 anos, DRC secundária à DRPA, há 2 anos em uso de EPO. No mês de entrada em HD desenvolveu anemia severa, também exigindo transfusões recorrentes para tratamento da anemia sintomática. Extensa investigação laboratorial e por imagem, sem chegar a uma conclusão definitiva. Em ambos os casos a presença de anticorpos anti-EPO foi confirmada por exames laboratoriais específicos. Terapia imunossupressora resultou em estabilização do quadro e Hb > 9,0 g/dl em ambos os pacientes, 6 meses após início do tratamento. Conclusão: APCV é condição rara entre pacientes dialíticos que recebem EPOHuR e deve ser lembrada como causa de anemia refratária. Seu manejo específico e diagnóstico laboratorial nem sempre acessível, tornando desafiadora a condução dos casos para o nefrologista.

Pure red cell aplasia with malignant thymoma: a rarity.

Pure red cell aplasia sometimes accompanies thymoma. Herein we report a PRCA patient with malignant thymoma. Only two Indian cases of PRCA with malignant thymoma have been reported so far and six cases in the world literature, to the best of our knowledge. This paper describes a malignant thymoma in a 40 year old male who later on developed pure red cell aplasia 7 months after thymectomy.

Parvovirus b19 infection in HIV patient with pure red cell aplasia.

Anemia in HIV-infected patients is a common clinical manifestation. We report on a 31-year-old Thai male, who had been HIV positive for 6 years, did not harbor any opportunistic infection, and had been receiving Highly Active Anti Retroviral Therapy (HAART) for one month, and who developed severe anemia. Investigation revealed pure red cell aplasia, suspected secondary to parvovirus B19 infection. This diagnosis was confirmed by the detection of parvovirus B19 DNA in his serum. He received blood transfusions for supportive treatment and continued on HAART to improve his immune status and to resolve the anemia. This case suggests that parvovirus B19 infection should be considered as a possible cause of anemia in HIV-infected individuals.

Pure red cell aplasia-a single centre experience

To determine the frequency of Pure Red Cell Aplasia [PRCA] in patients referred to Haematology Department of Holy Family Hospital, Rawalpindi for bone marrow examination. Single center descriptive study. The study was conducted at the Haematology Department of Holy Family Hospital Rawalpindi from 1st January 1999 to 31[st] September 2004. All patients referred to this department for bone marrow were included in this study. They comprised both male and female subjects of all ages. After taking a detailed history and conducting a complete physical examination blood samples were taken for complete blood picture. Bone marrow aspiration was done on all patients and trephine biopsies were taken only where indicated. Total of 1724 bone marrow aspirations biopsies were performed during this period, of which. 13 [0.75%] were diagnosed as Pure Red Cell Aplasia. 08/13 [61.5%] were males and 05/13 [38.4%] were females. The age range was from 1-52 years. Maximum number of patients belonged to 15-30 years age group. 01/13 [7.7%] was diagnosed as Diamond Blackfan Anaemia CDBA[2], 03/13 [23%] were associated with viral hepatitis. 04/13 [30.7%] cases had developed after some viral infection other than viral hepatitis. 01/13 [7.7%] had immune mediated PRCA, developing during the course of DAT positive hemolytic anaemia. 04/13 [30.7%] were idiopathic in origin. DBA patients initially responded well to corticosteroids but later developed resistance to steroids and became transfusion dependent. 02/13 [15.4%] patients also showed a good initial response to corticosteroid therapy and thus were labelled as Acute PRCA. 02/13 [15.4%] recovered spontaneously after diagnosis. Both these cases were children and thus diagnosed as cases of Transient Erythroblastopenia of Childhood [TEC]. PRCA is a rare disorder with a frequency of 0.75%. It is most commonly encountered in young adults secondary to a viral infection. Hepatitis is a major health hazard in our society and may play a significant role in the etiology of PRCA our patients

Unusual haematological alterations in rheumatoid arthritis.

Three cases of rheumatoid arthritis (RA), presenting with refractory anaemia, thrombocytopenia and peripheral lymphocytosis respectively, were observed. In all the cases haematological manifestations were unrelated to disease activity or drug toxicity. These patients were detected to have pure red cell aplasia (PRCA) (normocytic normochromic anaemia, reticulocytopenia and absence of erythroid precursors in the bone marrow), immune thrombocytopenia (IT) (absence of splenomegaly and presence of increased megakaryocytes in the bone marrow) and multiple myeloma (MM) (lytic lesions on skull, paraproteinaemia and bone marrow plasmacytosis) respectively. PRCA and IT responded to glucocorticoids. Association with these three haematological alterations has rarely been reported. Our report highlights the need to regularly monitor blood counts in patients with RA.

Acquired pure red cell aplasia--a case report.

A married female patient of 36 years with chronic anaemia, because of pure erythroid aplasia with a haemolytic component and hypothyroidism due to antithyroid auto-antibodies, was subsequently discovered as a case of systemic lupus erythematosus (SLE). She was treated with corticosteroid and immunosuppressive therapy and her anaemia was corrected. The response of erythroid aplasia to corticosteroid and other immunosuppressive agents suggests that immunological factors play a role in erythroid aplasia in SLE. The occurrence of red cell aplasia in association with a variety of immune phenomenon supports the concept that in SLE, erythroid aplasia may be of immune aetiology.

Non-Hodgkins lymphoma presenting as pure red cell aplasia.

An interesting case of Non-Hodgkins lymphoma presenting as pure red cell aplasia is being reported. Even though acquired pure red cell aplasia is not uncommon, lymphoma presenting as pure red cell aplasia is very rare. The patient responded to COP treatment and red cell transfusion and is on regular follow up. This appears to be the first report of such an association in Indian literature.

Aplastic crisis and leg ulceration: two rare complications of hereditary sideroblastic anaemia.

Aplastic crisis as a result of parvovirus infection is seen in a number of haematologic disorders characterized by decreased red cell survival, and leg ulceration due to unknown causes is seen in a number of haemolytic anaemias. Neither of the two has been reported in a case of sideroblastic anemia. We report one case with each of these complications in association with sideroblastic anaemia.

Pure red cell aplasia associated with essential thrombocythemia (a case report).

A rare case of erythroblastopenia associated with essential thrombocythemia (ET) is described. The patient had markedly elevated platelet count (5200 x 10(9)/1) and significant platelet dysfunction leading to extensive soft tissue and gastrointestinal hemorrhage. There was paucity of erythroid precursors in the bone marrow - a feature hitherto undescribed in ET. The thrombocytosis responded to well busulphan therapy but patient succumbed to fulminant infection consequent upon drug induced neutropenia.

Pure red cell aplasia with rheumatoid arthritis. A case report and review of literature.

Pure red cell aplasia (PRCA) is an extremely uncommon treatable manifestation of rheumatoid arthritis. Here we describe a case of long standing rheumatoid arthritis with severe refractory anaemia, which was proven to be due to PRCA.

Pure red cell aplasia in Thailand: report of twenty four cases.

Twenty four cases of pure red cell aplasia were reported. No underlying diseases were found in two cases. Of the 22 cases with secondary form, 10 were from infections, mostly gram negative organisms. Three cases had systemic lupus erythematosus, two had autoimmune hemolytic anemia. The following conditions were found in one each: thymoma, thyroid carcinoma, protein calorie malnutrition, rheumatoid arthritis, non-Hodgkin lymphoma and Sheehan's syndrome. Three patients died, two from uncontrolled infection, the other from uncontrolled SLE and subsequently systemic fungal infection. Only one of the 2 primary cases responded to immunosuppressive drugs. The majority of patients with underlying infections, PRCA resolved after the infections were treated. This is the first reported series of PRCA in Thailand.