[Persistent anemia after kidney transplantation in a 36-year-old male patient-an unusual cause]. / Persistierende Anämie nach Nierentransplantation bei einem 36-jährigen Patienten ­ eine ungewöhnliche Ursache.

An allogeneic kidney transplantation (match 1­1­0, cytomegalovirus, CMV, donor, D, +/recipient, R, - high risk) was performed in a 36-year-old patient. The patient was on dialysis due to a tubulointerstitial nephritis confirmed by biopsy 11 years previously. Posttransplantation there was a gradual decrease in the hemoglobin (Hb) level from 11.4 g/dl to 7.3 g/dl during the initial hospitalization period. Initially this was explained by the kidney transplantation and chronic fibrosing antral gastritis with erosions. Despite repeated transfusion of red cell concentrates, a refractory anemia persisted, which is why the patient presented several times at our clinic for further diagnosis and treatment. The presence of giant erythroblasts in the bone marrow and quantitative detection of parvovirus B19 (>900 million IU/ml DNA replications) was consistent with a virus-associated red cell aplasia. Intravenous immunoglobulin administration was established and showed long-term therapeutic success.

Pure Red Cell Aplasia and Antibody-Mediated Rejection: Double Trouble in 1 Kidney Transplant Recipient Solved by Intravenous Immunoglobulin Infusion: A Case Report.

Acquired pure red cell aplasia (PRCA) is characterized by severe normocytic (rarely macrocytic) and normochromic anemia, a low reticulocytes count in peripheral blood, and near absence of erythroid precursors in the bone marrow, with a normal level of erythropoietin. We describe a case of the kidney transplant recipient, diagnosed with PRCA induced with parvovirus B19 infection. Our case demonstrates that although this complication is rare, it should be considered in a differential diagnosis of anemia diagnostics in immunocompromised patients. In our case reduced immune response resulted from post-transplant immunosuppressive therapy. In our patient, apart from infection by parvovirus B19, graft dysfunction due to polyomavirus BK virus infection was also detected together with histologic and serologic features of antibody-mediated renal graft rejection. Considering the entire clinical picture, intravenous immunoglobulin therapy (IVIg) was successfully introduced.

The clinical characteristics and therapy response of patients with acquired pure red cell aplasia.

OBJECTIVE: To summarize the clinical characteristics of acquired pure red cell aplasia (PRCA) patients diagnosed in our hospital in the last 10 years. METHOD: The clinical features, immune state and treatment response of acquired PRCA patients diagnosed in our hospital from January 2007 to January 2017 were retrospectively analyzed. RESULTS: The results showed that thymoma (13.21%) and parvovirus B19 (11.32%) were the most common causes for secondary PRCA. Ferritin (Fer) levels and erythropoietin (EPO) levels were increased in PRCA patients. The total CR and PR rate of immunosuppressive therapy in our studies was 68.29% and 12.20%, respectively. Patients with EPO level >400 U/L and Fer level >200 ng/ml had significantly lower CR rate than others. The patients with EPO level >400 U/L also had longer hemoglobin recovery time than patients with EPO level ≤400 U/L. Patients treated with corticosteroids (CS) + cyclosporine A (CsA) had lower relapse rate compared to the CS group (29.17% vs. 80.00%, P < .05). CONCLUSION: Our data showed that patients with PRCA had high EPO and Fer levels. Thymoma and viral infections are the most common causes for secondary PRCA. The CS+ CsA group had lower relapse rate than CS group although response rate was similar. Increased EPO and Fer levels might be the negative factors for prognosis of acquired PRCA.

Chronic persistent parvovirus B19 bone marrow infection resulting in transfusion-dependent pure red cell aplasia in multiple myeloma after allogeneic haematopoietic stem cell transplantation and severe graft versus host disease.

INTRODUCTION: We report a chronic persistent Parvovirus B19 (PVB19) infection despite long-term immunoglobulin substitution intravenous immunoglobulin (IVIG) and tapering of immune-suppressive therapy in a 41-year-old patient after allogeneic haematopoietic stem cell transplantation (alloHSCT) and long-term immune-suppressive therapy due to a steroid-refractory graft versus host disease (GvHD). CLINICAL COURSE: More than 18 month after alloHSCT the patient acquired a de novo transfusion-dependent pure red cell aplasia (PRCA) due to a PVB19 infection. Despite prompt tapering of GvHD-directed therapy and application of various IVIG regimens, transfusion-dependent anaemia (fourerythrocyte concentrates a month) persisted, and a high PVB19 replication is still evident for more than 3.5 years. Virological analysis at different time points showed a very high PVB19 load in the blood (range: 6.79E9-1.56E11), as well as highly elevated PVB19-IgG (range: 1.95-3.34) and -IgM (range: 1.97-9.74) levels in serology testing. Other virological parameters were not significantly elevated. After 30 months, a bone marrow (BM) examination still revealed a highly dysplastic erythropoiesis without any cellular maturation, and a high-grade expression of PVB19 within the dysplastic erythropoietic progenitor cells, consistent with a PRCA due to a PVB19 infection of the BM. We suggest that PRCA was most probably caused by a primary PVB19 infection of unknown source following alloHSCT with a PVB19-negative donor. CONCLUSION: PRCA due a PVB19 infection of the BM may persist over a long-time, despite prolonged administration of various IVIG regimen and tapering of GvHD-directed therapy. The case emphasizes the importance of PVB19 monitoring in heavily pre-treated haematological patients. Currently, PVB19-directed treatment options are extremely limited and optimized therapeutic strategies are urgently needed.

Holoprosencephaly and Pure Red Cell Aplasia in a Feline Leukaemia Virus-Positive Kitten.

A 9-month-old, female, domestic longhair cat with severe anaemia tested positive for feline leukaemia virus (FeLV) and was humanely destroyed and submitted for necropsy examination. Gross findings included a non-divided rostral telencephalon, consistent with semilobar holoprosencephaly. Histological examination of the bone marrow revealed an almost complete absence of erythroid precursor cells, consistent with pure red cell aplasia, and mild to moderate myelofibrosis. This case demonstrates a very unusual central nervous system defect, as well as an atypical presentation of pure red cell aplasia, in a FeLV-positive kitten.

A case of recurrent autoimmune hemolytic anemia during remission associated with acute pure red cell aplasia and hemophagocytic syndrome due to human parvovirus B19 infection successfully treated by steroid pulse therapy with a review of the literature.

The patient was a 47-year-old man diagnosed as having autoimmune hemolytic anemia (AIHA) in April 2011. He also had a congenital chromosomal abnormality, a balanced translocation. Treatment with prednisolone (PSL) 60 mg/day resulted in resolution of the AIHA, and the treatment was completed in November 2011. While the patient no longer had anemia, the direct and indirect Coombs tests remained positive. In May 2013, he developed recurrent AIHA associated with acute pure red cell aplasia (PRCA) and hemophagocytic syndrome (HPS) caused by human parvovirus B19 (HPV B19) infection. Tests for anti-erythropoietin and anti-erythropoietin receptor antibodies were positive. Steroid pulse therapy resulted in resolution of the AIHA, PRCA, as well as HPS. The serum test for anti-erythropoietin antibodies also became negative after the treatment. However, although the serum was positive for anti-HPV B19 IgG antibodies, the patient continued to have a low CD4 lymphocyte count (CD4, <300/µL) and persistent HPV B19 infection (HPV B19 DNA remained positive), suggesting the risk of recurrence and bone marrow failure.

Persistent parvovirus B19 infection resulting in red cell aplasia after allogeneic hematopoietic stem cell transplantation.

Persistent parvovirus B19 (PVB) infection has been reported sporadically in immunocompromised patients including hematopoietic stem cell and solid organ transplant recipients. However, the pathogenesis of persistent infection has yet to be fully elucidated. We report here a patient with multiple myeloma developing red cell aplasia during the hematopoietic recovery after allogeneic hematopoietic stem cell transplantation (HSCT) caused by PVB. The patient had already had PVB viremia before transplantation and remained asymptomatic. The route of PVB transmission was considered to be direct contact with the patient's family member with primary PVB infection 1 month before transplantation. Treatment with intravenous immunoglobulin resulted in prompt resolution of anemia. These findings suggest that monitoring of PVB DNA is recommended for patients undergoing HSCT and having contact with individuals with documented PVB infection, even if they are asymptomatic.

Anemia crônica no pós-transplante renal: parvovirose B19 / Posttransplant chronic anemia: parvovirus B19

A anemia é frequente em pacientes após o transplante renal (TxR) e sua prevalência varia conforme o tempo pós-transplante e os critérios diagnósticos empregados. A infecção pelo Parvovírus B19 (PV B19) é causa subdiagnosticada de anemia nesta população. Para ilustrar a epidemiologia e espectro clínico, apresentamos caso de PV B19 que evoluiu com aplasia pura de série vermelha (APSV), ressaltando as dificuldades do diagnóstico e tratamento. O emprego da detecção do DNA viral pela reação em cadeia da polimerase e do diagnóstico das alterações da morfologia da medula óssea são particularmente úteis para o diagnóstico no paciente transplantado imunossuprimido que falha na produção da resposta humoral contra o PV B19.

Anemia is frequent in kidney transplant patients, and its prevalence varies according to posttransplant time and the adopted diagnostic criteria. Parvovirus B19 (PV B19) infection is an underdiagnosed cause of anemia in this particular population. To illustrate epidemiologic and clinical data regarding it, we present a case of PV B19 infection complicated by pure red cell aplasia (PRCA), pointing out the pitfalls we encountered in diagnosis and treatment. The use of viral DNA detection by polymerase chain reaction (PCR), and correct interpretation of morphological features of bone marrow histology are particularly important for the diagnosis of this condition in kidney transplant patients, who fail to develop a proper humoral response against PV B19, thus importantly decreasing the sensitivity of serological methods in this setting.

Pure red cell aplasia caused by Parvo B19 virus in a kidney transplant recipient.

Parvo B19 is a single stranded DNA virus, which typically has affinity for erythroid progenitor cells in the bone marrow and produces a severe form of anemia known as pure red cell aplasia. This condition is particularly worse in immunocompromised individuals. We herein report a young Nepali male who developed severe and persistent anaemia after kidney transplantation while being on immunosuppressive therapy. His bone marrow examination revealed morphological changes of pure red cell aplasia, caused by parvovirus B19. The IgM antibody against the virus was positive and the virus was detected by polymerase chain reaction in the blood. He was managed with intravenous immunoglobulin. He responded well to the treatment and has normal hemoglobin levels three months post treatment. To the best of our knowledge, this is the first such case report from Nepal.

Pure red cell aplasia caused by parvovirus B19 in two patients without chronic hemolysis.

Infection with human parvovirus B19 (PVB19) induces acquired pure red cell aplasia (PRCA). Chronic hemolytic anemia is well known as an underlying condition. However, additional factors have been recognized to accompany parvoviral PRCA; however, there are only limited reports on iron-deficiency anemia (IDA) and rituximab-induced B-cell dysfunction. We report two patients with PVB19-associated PRCA confirmed by positivity of viral DNA. Although they had no chronic hemolysis, patient 1 had IDA, and patient 2 had remitted small-lymphocytic lymphoma treated with rituximab-containing chemotherapy. Absence of reticulocytes in peripheral blood and marked depletion of erythroid precursors in bone marrow were observed both. Whereas patient 1 received only symptomatic therapy because anemia was not severe, patient 2 was treated with steroids, as PRCA etiology was at first uncertain, and immunological PRCA was not excluded. Both showed rapid increase of reticulocyte counts and recovery from anemia. Although immunoglobulin is considered effective for parvoviral PRCA, notable adverse reactions have been reported. When anemic symptom is not severe, reticulocyte observation only is recommended. The effects of steroids should also be re-evaluated. Optimal treatment according to disease severity remains to be established.

[Parvovirus B19-induced pure red cell aplasia in a liver transplant recipient].

Parvovirus B19 infection is known to cause chronic anemia in immunocompromised hosts, including organ transplant recipients. We report the first case of liver transplant recipient with parvovirus B19-induced pure red cell aplasia in Korea. A 57-yr-old female patient with hepatocellular carcinoma due to hepatitis C virus received a liver transplantation. Two months later, anemia developed and she received periodic red blood cell transfusions. However, chronic anemia persisted and bone marrow examination was performed 8 months after transplantation. Bone marrow aspiration smears showed markedly reduced erythroid precursors with atypical giant pronormoblasts and nuclear remnants with viral inclusions, and characteristic lantern cells were observed in biopsy sections. In addition, parvovirus B19 DNA PCR was positive. She was diagnosed as parvovirus B19-induced pure red cell aplasia and her anemia was improved following intravenous immunoglobulin therapy.

Parvovirus B 19 (PVB19) induced pure red cell aplasia (PRCA) in immunocompromised patient after liver transplantation.

Presented here is a case of human parvovirus B19 (PVB19) induced pure red-cell aplasia (PRCA) in immunocompromised patient after orthotopic liver transplantation (OLT). PVB19 is a small, single-stranded DNA whose target cell is the erythroid progenitor in bone marrow. Manifestations of PVB19 infection vary with the immunologic status of the patient, ranging from asymptomatic to severe infections and PRCA. Post-transplant PRCA is induced either by immunosuppressive agents or PVB19. In the presented case, bone marrow aspiration characterized by the absence of mature erythroid precursors and detection of PVB19 DNA in blood led to treatment with high-dose intravenous human immunoglobulins (IVIG) and subsequent recovery of erythropoiesis. Due to insufficient antibody response in immunocompromised patients, suppression of the PVB19 infection is delayed and repetitive treatments may be administrated in attempt of reversing PRCA.

Pure red cell aplasia associated with cytomegalovirus infection.

SUMMARY: A 3-month-old boy presented with progressive pallor since the age of 1 month. Hemogram and bone marrow aspirate were suggestive of pure red cell aplasia. Serum bilirubin and aminotransferases were elevated. Cytomegalovirus serology and DNA polymerase chain reaction were positive. Fetal hemoglobin was normal and Parvovirus B19 DNA polymerase chain reaction was negative. Through this case report, we wish to highlight a rare, might be causative association of cytomegalovirus infection with pure red cell aplasia.

Acute human parvovirus B19 infection and nephrotic syndrome in patients with sickle cell disease.

Acute Human Parvovirus B19 (HPV B19) infection is the major cause of transient red cell aplasia (TRCA) and acute anaemia in patients with sickle cell disease (SCD). We report three cases of patients who developed nephrotic syndrome (NS) with chronic sequelae after initially presenting with HPV B19-associated TRCA. There was no correlation between evidence of HPV B19 infection and impaired renal function in our cohort of adult sickle cell patients. This is consistent with a view that although NS is potentially a rare complication of symptomatic acute HPV B19 infection, exposure to HPV B19 is not associated with an increased risk of renal disease.