Epoetin-induced autoimmune pure red cell aplasia

During the first 10 yr of therapy with recombinant human erythropoietin ([EPO]), only three cases of antibody-associated pure red cell aplasia have been described in patients who were treated with EPO, whereas several millions of patients have received this treatment. Thus, the possibility for epoetin to induce the formation of anti-EPO antibodies was considered extremely low. However, since 1998, a significant increase in the number of cases of EPO-induced pure red cell aplasia has been found in patients with chronic kidney disease with a peak in 2001 and 2002. The incidence rate seems now to be back to the baseline level. The change in formulation of epoetin a sold outside the United States seems to be the cause of these antibodies.     

Epoetin-induced pure red cell aplasia: diagnosis and treatment

PURPOSE OF REVIEW: Antibody-mediated pure red cell aplasia is now recognized as a rare complication of erythropoiesis-stimulating agent therapy. The incidence of this adverse effect peaked in 2002, but new cases still appear sporadically. The aim of this review is to discuss the latest opinions regarding the detection and management of this condition. RECENT FINDINGS: The diagnosis of classical erythropoiesis-stimulating agent induced pure red cell aplasia is made by a constellation of clinical features, including severe transfusion-dependent anaemia, reticulocytopenia, low or absent erythroblasts in the bone marrow, and the presence of circulating antierythropoietin antibodies. Recently, some cases have been reported in which the bone marrow findings show red cell hypoplasia rather than aplasia; this may represent earlier presentations of the same condition. SUMMARY: Management of pure red cell aplasia as a complication of erythropoiesis-stimulating agent therapy consists of stopping the drug and implementing an immunosuppressive regimen to reduce or abolish erythropoietin antibody production. A recent animal study suggested that a possible alternative strategy may be to administer a novel peptide-based erythropoietin receptor agonist called Hematide that does not cross react with antierythropoietin antibodies, and will allow ongoing stimulation of erythropoiesis; this is the subject of a current clinical trial.     

Thymoma with pure red cell aplasia and Good's syndrome

Thymoma patients with pure red cell aplasia (PRCA) or hypogammaglobulinemia (Good's syndrome) are rare, whereas those with both PRCA and Good's syndrome are even rarer. Here we present the case report of a 70-year-old woman with invasive thymoma and simultaneous PRCA and Good's syndrome, who achieved complete PRCA remission after thymectomy.     

A case of thymoma with pure red cell aplasia]

A 71-year-old man was admitted to the hospital because of general fatigue. There were few reticulocytes in the peripheral blood and no erythroblasts in the bone marrow. Chest CT revealed an anterior mediastinal tumor. Under a diagnosis of thymoma with PRCA, extended thymothymectomy was performed. Histological diagnosis was mixed type thymoma with no invasive growth beyond the capsule. Administration of predonisolone following surgery was not effective for PRCA. Otherwise, peripheral blood counts were significantly improved following occasional onset of acute bronchitis.     

Anterior mediastinal exenteration for thymoma associated with pure red cell aplasia

A 46-year-old female bad thymoma associated with pure red cell aplasia, a relatively uncommon entity. Anterolateral thoracotomy in supine position offered excellent exposure for exenteration of anterior mediastinum. Steroids and cyclophosphamide were administered postoperatively. She remains stable one year after surgery. The incidence, clinical features, pathology, pathogenesis, management and prognosis of thymoma with pure red cell aplasia are reviewed.     

Bronchocentric granulomatosis associated with pure red cell aplasia and lymphadenopathy.

Bronchocentric granulomatosis developed in a patient with previously diagnosed pure red cell aplasia and lymphadenopathy. There was an excellent response to corticosteroid treatment. An immunological pathogenesis common to bronchocentric granulomatosis and pure red cell aplasia is suggested.     

Antierythropoietin antibody-induced pure red cell aplasia: posttransplant evolution

Pure red cell aplasia is a rare complication of recombinant human erythropoietin (rHuEPO) treatment, which physicians should consider once the more frequent causes of hyporegenerative anemia have been excluded. To our knowledge, no pediatric cases have been described. In our patient, cyclosporin A treatment enabled a reduction in the number of transfusions and the risk of hyperimmunization. After transplantation, our patients hemoglobin level has remained normal and stable.     

Acquired pure red cell aplasia in a hemodialyzed patient

A 68-year-old male had end-stage renal disease secondary to hypertension. He was placed on chronic dialytic therapy and was given recombinant human erythropoietin (epoetin) for renal anemia. One month later, rapidly progressing anemia was noted. The anemia was unresponsive to maximal doses of epoetin and the patient soon became transfusion-dependent. Erythroid hypoplasia was demonstrated by bone marrow biopsy. A detailed search for the cause of the erythroblastopenia revealed nothing. A diagnosis of acquired pure red cell aplasia was made. The use of immunosuppressive agents improved the patient's symptoms and laboratory data. Antibodies for erythropoietin (EPO) were negative after the treatment. It is suggested that patients with EPO-resistant anemia with no obvious etiology should be examined for underlying hematologic disorders.     

Azathioprine-induced pure red cell aplasia: case report and review

The major adverse effect of azathioprine is its myelotoxicity, with leukocytes being affected more commonly than the other bone marrow elements. Although megaloblastic change is frequent, reportedly seen in 16% to 82% of bone marrow aspirates, long-term use of azathioprine rarely causes severe anemia. We report a case of refractory pure red cell aplasia resulting from long-term use of azathioprine in a renal transplant recipient and examine the possible underlying mechanisms. There was no response to dose reduction or to erythropoietin administration. However, there was immediate recovery after complete drug withdrawal. A review of the literature revealed that only ten cases of azathioprine-induced red cell aplasia have so far been described, all in transplant recipients.     

A case of pure red cell aplasia with hypogammaglobulinemia appearing after thymo-thymectomy]

We present a case of 83-year-old woman with pure red cell aplasia appearing eight months after thymo-thymectomy for an invasive thymoma. She underwent thymo-thymectomy for an invasive thymoma in July 1996. Preoperative examination revealed neither anemia nor hypogammaglobulinemia. About eight months after the operation, she was readmitted because of anemia and hypogammaglobulinemia. Bone marrow aspiration revealed absence of erythroblasts and chest CT revealed norecurrence of thymoma. Her anemia had responded to ciclosporin.     

胸腺瘤合并单纯红细胞再生障碍性贫血临床特点(附3例报告)

目的探讨胸腺瘤合并纯红再障的诊断和治疗。方法3例胸腺瘤合并纯红再障患者,均手术切除胸腺瘤,并于术后常规胸腺区放疗,观察术后纯红再障的缓解情况。对不能缓解者,给予皮质激素及免疫抑制剂治疗。结果2例术后达临床治愈,1例术后给予激素及免疫抑制剂治疗取得缓解或明显进步。结论胸腺瘤切除-术后胸腺区放疗-皮质激素及免疫抑制剂的运用是胸腺瘤合并纯红再障患者较理想的治疗模式。     

Concomitant thymectomy and cardiac operation in a patient with pure red cell aplasia

Pure red cell aplasia is a rare condition resulting in severe anemia. Medical therapy is indicated, unless a thymoma is present. In patients with concurrent cardiac pathology requiring operation, simultaneous operation should be contemplated to avoid risky resternotomy. We describe an exceptionally rare case of a patient with pure red cell aplasia secondary to a thymoma who underwent concomitant thymectomy and coronary artery grafting with a successful surgical outcome.     

Surgery for the thymoma combined with pure red cell aplasia and myasthenia gravis

Pure red cell aplasia (PRCA) and myasthenia gravis (MG) are respectively combined with thymoma, however, these 3 complications are extremely rare coexisted as a clinical triad. A 73-year-old female with mediastinal tumor found in 2000 was pointed out anemia in June 2002. As PRCA was diagnosed by the bone marrow examination, blood transfusion had been performed. By a chest computed tomography (CT), a thymoma in size of 7 x 5 cm in diameter was recognized in the anterior mediastinum. The serum level of anti-acetylcholine receptor antibody was elevated to be 35 nmol/l. MG was simultaneously diagnosed with a decreased power of neck muscle. The extended thymectomy was performed in August 2002, and pathological diagnosis disclosed a 'type AB' by World Health Organization (WHO) classification. After the operation, the decreased power of neck muscle had been improved, however, PRCA had not been remitted in the early-postoperative term. Blood transfusion had been required (2-4 units/1-2 weeks) for the postoperative 7 months' term. A cyclosporin (250 mg/day) as an adjuvant therapy was administered in April 2003. One month later, the patient's serum level of Hb had been over 10 g/dl without blood transfusion. The patient has been followed up with reducing the dose of cyclosporin. Conclusions: Surgery for a thymoma combined with PRCA and MG was effective for MG but not for PRCA in an early-postoperative term, however, a multimodality therapy with immunosuppressant as a postoperative adjuvant should bring a favorable outcome to patient's clinical data, and the postoperative long-observation must be critical in this case.