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Bone marrow smear showing two giant proeythroblasts. One intact with intranuclear eosinophilic inclusion body like nucleoli. Arrow points to 'dog ear'
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Parvo B19 is a single stranded DNA virus, which typically has affi nity 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 k...
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Pure red cell aplasia (PRCA) is a rare syndrome that only affects the erythroid lineage. It is defined by a normocytic, normochromic anemia with a marked reticulocytopenia and severe reduction or absence of erythroid precursors in the bone marrow. Treatment of primary, idiopathic PRCA is immunosuppressive therapy. Although it is rare, isolated cyto...
Dysregulation of T cell-mediated immunity is considered a major pathophysiological mechanism of acquired pure red cell aplasia (PRCA), such as idiopathic PRCA, large granular lymphocytic leukemia-associated PRCA, and thymoma-associated PRCA. Although STAT3 mutations are frequently detected in PRCA patients, other mutational profiles and their invol...
Citations
... 3 Parvovirus B19 has high affinity for erythroid precursor cells in the bone marrow producing severe anemia (Pure red cell aplasia). 4 Here we describe two case reports of severe anemia secondary to Parvovirus B19 infection in kidney transplant recipients. ...
... IVIG replaces the deficit by neutralizing antibodies in the patient. 3,4,8 IVIG at a dose of 0.4-1.0 g/kg body weight daily for 5-7 days appears to be clinically most effective treatment in most cases with no subsequent adverse effects reported. ...
... 8 also important to avoid the use of erythropoietin to treat the PV B19 induced anemia, as this can cause resistance of the virus to the proven treatment. 4 For patients having Parvovirus B19 infection with refractory anemia and fail to recover with IVIG, replacement of tacrolimus with cyclosporine-A may be considered. 9 ...
Parvovirus B19 infection should be contemplated as one of the differential diagnoses of persistent anemia in transplanted patients. There must be high index of suspicion of Parvovirus B19, when post-transplant patients present with refractory and severe anemia with reticulocytopenia and all the other common causes of anemia such as blood loss, adverse effects of immunosuppressant agents and graft dysfunction has been ruled out. In suspected patients, diagnosis is confirmed by serological tests (IgM and IgG), PCR from blood and/or bone marrow and by bone marrow biopsy finding of pure red cell aplasia. Intravenous immunoglobulin (IVIG) is the treatment of choice and highly rewarding. Here we are reporting two cases of post-transplant Parvovirus infection, one in an adult lady and second in an adult man who underwent live renal transplantation recently.
... The anemia due to PRCA is a severe anemia, in which a reticulocyte count is generally less than 1%, and mature erythroblasts present less than 0.5% in the bone marrow (Fallahi et al., 2014). PRCA can develop in patients with PVB19 infection (Kurukulasuriya et al., 2011;Baral et al., 2012), erythropoietin therapy (Casadevall et al., 2002;Macdougall et al., 2012), ABO-incompatible transfusion (Rowley et al., 2011), and stem cell transplantation (Stussi et al., 2009). PVB19 may cause PRCA due to its viral tropism and direct cytotoxicity to erythroid progenitor cells (Heegaard and Brown, 2002). ...
... High-dose intravenous immunoglobin therapy should be considered for PRCA caused by PVB19 infections and erythropoietin therapy. PRCA may be reversible by immunoglobulin within a few months (Kurukulasuriya et al., 2011;Baral et al., 2012). ...
Renal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: (1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE), and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents, and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria, or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival.
Parvovirus B19 has special affinity to erythroid progenitor cells leading to destruction and inhibition of erythropoiesis. One of its presentations is pure red cell aplasia in patients receiving immunosuppressive medications after organ transplantation. Intravenous immunoglobulin (IVIG) and reduction of immunosuppressive medication has been used for treatment but the effects of IVIG may be temporary. Here we present a case of Relapsing infection due to Parvovirus B19 after IVIG in a renal transplant recipient in Nepal. This case shows that in renal transplant patients presenting with anemia and low reticulocyte count, Parvovirus B19 infection should be suspected. Treatment with IVIG has good results but there may be relapse of infection.
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.
Parvovirus B19 (PV B19) infection can cause pure red cell aplasia (PRCA) and severe normochromic anemia resistant to treatment with erythropoietin in renal transplant recipients. Active parvovirus infection usually develops in the first months after kidney transplantation (KT), but is not always accompanied by clinical symptoms. The incidence of PV B19-associated anemia is low - not more than 1–1.5 %. A confirmation of the etiology of the disease, in addition to the characteristic histological picture of the bone marrow (a decrease in the number of erythrokaryocytes of less than 5% with preserved myelopoiesis and megakaryopoiesis, the appearance of single giant pronormoblasts), is the detection of PV B19 DNA in the blood and / or bone marrow. The detection of specific IgM antibodies to parvovirus plays a less significant role in the diagnosis of active PV B19 infection in patients after KT receiving immunosuppressive therapy and should not be used as the only diagnostic method. There is no specific antiviral treatment for PV B19 infection, therefore other approaches to therapy are used: reduction of immunosuppression, transfusion of red blood cells, administration of intravenous immunoglobulin (IVIG). The article describes the clinical observation of a 33-year-old patient with stage 5 CKD who developed severe normochromic anemia resistant to treatment with erythropoietin 4 weeks after a successful KT. A cytological examination of the bone marrow revealed PRCA, and a large number of copies of PV B19 DNA were detected in the patient’s blood, while antibodies to parvovirus IgG and IgM were not revealed. A decrease of immunosuppression (withdrawal of mycophenolic acid), repeated administration of IVIG in a total dose of 147 g resulted to lasting normalization of red blood cells number and hemoglobin level after five months of treatment. The function of the renal transplant remained normal throughout the observation period.
Background
Anemia is present even in long-term observation after kidney transplantation. Observational study results indicate the presence of chronic post-transplantation anemia in 1 in 3 recipients. An extreme form of erythroid line dysfunction is pure red cell aplasia (PRCA). It may be caused by immunosuppressive treatment per se or a side effect, opportunistic pathogen activation. Parvovirus B19 (PV B19) infection is quite likely the cause of refractory normocytic anemia in immunocompromised patients.
Case Report
In this case report we discuss biological and clinical features of this phenomenon and the treatment strategies, based on 2 PRCA cases in kidney transplant recipients. Additionally, a systematic review of published reports of PV B19 related PRCA in kidney recipients is presented.
Conclusions
PV replication should be ruled out in cases of persistent and/or refractory anemia after kidney transplantation. The established first-line treatment of PRCA is passive immunization. Taking into account cost effectiveness, a decrease in immunosuppression load is reasonable under careful control of allograft function.
Thymic involution The thymus gland can be the site of origin of a wide variety of benign, low-grade malignant, and malignant neoplasms 1,2. Although these tumors are relatively infrequent in the general population, they have elicited a great deal of interest in the medical literature because of their association with myasthenia gravis and other neurological diseases, red cell aplasia, extrathymic malignancies, and other diseases 3-5 (Table 6.1). Microscopically, the thymus in acute involution shows widespread lympholysis and infiltration by macrophages with large somewhat foamy cytoplasm (Fig. 5.1), giving the gland a typical “starry-sky” appearance (Fig. 5.2). These changes are most prominent in the thymic cortex. Studies using immunohistochemistry have demonstrated that the epithelial network remains unchanged in the acutely involuted thymus, while there is a progressive loss of cortical immature proliferating lymphoid cells and medullary interdigitating cells. The degree of acute thymic involution in infancy and childhood correlates with the duration of an acute illness.
