Resistant anemia in a kidney transplant recipient: Pure red cell aplasia due to parvovirus B19 infection.

Anemia in kidney transplant recipients can stem from a diverse array of etiologies, including dietary deficiencies, inflammatory processes, allograft dysfunction, as well as viral and bacterial infections. We present a case of refractory anemia in a 49-year-old male patient occurring within the initial month following a kidney transplant, which persisted despite numerous transfusions, posing a formidable challenge. The patient was maintained on the standard immunosuppressant regimen-Tacrolimus, Mycophenolate, and Prednisolone. Diagnostic evaluations eliminated well-established causes such as dietary deficiencies, gastrointestinal losses, and prevalent infections. Subsequently, after viral PCR testing, a diagnosis of Pure Red Cell Aplasia (PRCA) due to infection with parvovirus B19 was made. Although the patient had a reduction in the immunosuppression drugs and received a course of Intravenous Immunoglobulins (IVIG) on two separate occasions spanning two months, the anemia relapsed. Subsequently, after an additional dose of IVIG with further modification and reduction of the immunosuppressant regimen, including stopping the mycophenolate and switching tacrolimus with cyclosporine, the patient ultimately achieved successful resolution of his symptoms and a significant decrease in viral load. Our case highlights the significance of unconventional etiologies when confronted with anemia in the setting of kidney transplantation. Furthermore, it also provides further insights into therapeutic avenues for addressing PRCA in kidney transplant recipients.

Nationwide survey of intrauterine blood transfusion for fetal anemia in Japan.

AIM: The present study investigated the current situation regarding intrauterine blood transfusion (IUT) for fetal anemia in Japan. METHODS: We conducted a nationwide, multicenter, retrospective cohort questionnaire survey for cases that underwent IUT from 2011 to 2015. The questionnaire required perioperative information, indications, details of the procedure, procedure-related complications, and neonatal morbidity. RESULTS: A total of 100 IUT procedures were performed in 66 cases at 19 institutions during the study period. The most frequent indication of IUT was complicated monochorionic diamniotic (MCDA) twins in 28 (42.4%) cases, followed by 16 (24.2%) cases of red-cell alloimmunization, and 10 (15.2%) cases of parvovirus B19 infection. IUT was performed through the umbilical cord in the vast of majority cases (92%). Bleeding from the IUT site was the most common adverse event (40%). Two cases (2%) underwent emergency cesarean section after the procedure. There were no cases of rupture of membrane or intrauterine infection after IUT. The neonatal survival rate was 77.3% in the 66 total cases and 64% in the hydrops cases. The neonatal survival rates in MCDA twins, red-cell alloimmunization, and parvovirus B19 infection were 75%, 93.8%, and 70%, respectively. CONCLUSIONS: IUT was performed for mainly three indications in Japan: MCDA twins, red-cell alloimmunization, and parvovirus B19 infection. The incidences of severe adverse events seemed very low. The outcomes after IUT were favorable with variations in survival rates according to indications. However, further studies with long-term follow-up will be required to assess the effectiveness of IUT, especially for complicated MCDA twins.

Parvovirus B19 activates in vitro normal human dermal fibroblasts: a possible implication in skin fibrosis and systemic sclerosis.

OBJECTIVE: Fibrosis is the most characteristic pathological hallmark of SSc, a connective tissue disease characterized by vascular and immunological abnormalities, inflammation and enhanced extracellular matrix production, leading to progressive fibrosis of skin and internal organs. We previously demonstrated that parvovirus B19 (B19V) can infect normal human dermal fibroblasts (NHDFs) and that B19V persists in SSc fibroblasts. In this study, we investigated whether parvovirus B19V is able to activate in vitro NHDFs and to induce in these cells some phenotypic features similar to that observed in the SSc fibroblasts. METHODS: We preliminarily analysed the time course of B19V infection in cultured NHDFs, then we investigated the ability of B19V to induce cell migration, invasive phenotype and mRNA expression of some profibrotic and/or proinflammatory genes. RESULTS: We confirmed our previous findings that B19V infects NHDFs, but the infection is not productive. After incubation with B19V, NHDFs showed a significant increase of both migration and invasiveness, along with mRNA expression of different profibrotic genes (α-SMA, EDN-1, IL-6, TGF-ß1 receptors 1 and 2, Col1α2), some genes associated with inflammasome platform (AIM2, IFI16, IL-1ß, CASP-1) and genes for metalloprotease (MMP 2, 9 and 12). CONCLUSION: These data suggest that B19V can activate dermal fibroblasts and may have a role in the pathogenesis of fibrosis. B19V-induced fibroblast migration and invasiveness could be due to the B19V-associated MMP9 overexpression and activation. Moreover, the up-regulation of MMP12, typical of SSc, could link the B19V infection of fibroblasts to the anti-angiogenic process.

Look-back study on recipients of Parvovirus B19 (B19V) DNA-positive blood components.

BACKGROUND AND OBJECTIVES: To assess the relevance of Parvovirus B19 (B19V) DNA at low to intermediate concentrations in blood donors for the recipients of their blood components. MATERIAL AND METHODS: We studied recipients of B19V DNA-positive blood components [red blood cell concentrates (RBCs), pooled platelet concentrates and fresh frozen plasma]. This included archived pretransfusion samples as well as follow-up samples investigated by ELISA or NAT and genome sequence analysis. RESULTS: In 132 out of 424 recipients, we could detect no anti-B19V IgG before transfusion. In 67 out of 132 sero-negative recipients, a follow-up sample was available. Sixty-five of these received blood components from donors with <10(4) IU B19V DNA/ml plasma and had no evidence of transfusion-transmitted (TT)-B19V infection. Homology in genome sequences in donor and recipient provided evidence for a TT-B19V infection in two recipients. Both patients received RBC containing 3.4 × 10(6) and 1.8 × 10(4) IU B19V DNA/ml plasma, respectively. The anti-B19V IgG titres in the donors were 2 and 76 IU/ml plasma, respectively. The antibodies in the second donor were directed against capsid proteins and are thus considered as potential neutralizing antibodies. CONCLUSIONS: TT-B19V infections through blood components with low (<10(4) IU/ml plasma) B19V DNA concentrations did not occur in our study. One of the TT-B19V infections occurred from RBC with intermediate B19V DNA concentration despite the presence of potential neutralizing antibodies in the donor, but its clinical significance was low.

Persistence of Parvovirus B19 (B19V) DNA and humoral immune response in B19V-infected blood donors.

BACKGROUND AND OBJECTIVES: Parvovirus B19 (B19V) DNA seems to persist in the plasma of B19V-infected blood donors. The relevance of this for recipients of single-donor blood components is yet unclear. MATERIAL AND METHODS: We studied serial archive and follow-up samples from 75 B19V-infected blood donors to obtain more data about the duration and degree of viraemia and the presence of IgG and IgM anti-B19V. IgG antibodies were further characterized by Western blot analysis in 29 donors. RESULTS: In 411 B19V DNA-positive samples collected, we found high concentrations (>10(6) IU B19V DNA/ml plasma) in five. B19V DNA persisted for a mean of 21·5 months (range: 2·3-52·4; 95% confidence interval, 19·1-23·9 months) in all donors. Only 15 such samples had either no or low-titre IgG anti-B19V. IgG antibodies were predominantly directed against epitopes on the minor capsid protein VP1, thus probably of neutralizing type with high avidity. IgM anti-B19V was detectable in 9/13 samples with high DNA concentrations. CONCLUSIONS: The vast majority of single-donor blood components with detectable B19V DNA are probably not infectious for their recipients because DNA is at only low levels and the donors also have potentially neutralizing antibodies with high avidity. Anti-B19V IgM testing does not identify every donation with high B19V DNA concentrations, but, in addition to B19V NAT testing, donors with persistent IgG anti-B19V might be considered 'B19V-safe' for single-donor blood components.

Pure Red Cell Aplasia Secondary to Parvovirus B19 Infection as a Rare Cause of Anemia in a Dialysis Patient.

Parvovirus B19 infection can cause chronic pure red cell aplasia in immunosuppressed hosts or acute and transient aplastic crisis in immunocompetent hosts. In dialysis patients, only transient aplastic crisis induced by parvovirus B19 infection has been reported. We herein report the first case of an adult dialysis patient who developed chronic pure red cell aplasia associated with parvovirus B19 infection. Repeated pneumonia and heart failure may contribute to an immunocompromised status, making the patient more vulnerable to parvovirus B19 infection. This case expands on the differential diagnosis of chronic anemia in patients undergoing dialysis.

Immune Cell Profiles of Patients with Sickle Cell Disease during Parvovirus B19-Induced Transient Red Cell Aplasia.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

Parvovirus B19-associated graft failure after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Parvovirus B19 (PVB19) infection has been implicated in allograft failure or dysfunction in solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the literature is limited. CASE: Two pediatric patients were diagnosed with PVB19 infection around the time of allo-HSCT graft failure. Both cases were secondary graft failure and required second allo-HSCT. CONCLUSION: There are many risk factors and potential confounders in determining the exact etiology of graft failure after allo-HSCT. These two cases highlight the importance of including PVB19 in the diagnostic evaluation for graft failure. PVB19 infection may be an important risk factor for allo-HSCT graft failure.

Human parvovirus B19 infection in an immunocompromised host.

Serologic testing may be negative in immunocompromised hosts due to inadequate IgG and IgM response. The classic bone marrow findings of viral inclusions and giant proerythroblasts are pathognomonic for active infection and should prompt initiation of therapy regardless of serologic results.

Recurrent parvovirus B19 infection-associated pure red cell aplasia in a kidney transplant patient.

Posttransplant anemia is a common complication after kidney transplantation. Parvovirus B19 (PVB19) infection can induce pure red cell aplasia (PRCA) in immunosuppressed transplant patients. We herein report a case of recurrent PVB19-associated PRCA in a kidney transplant patient. A 49-year-old woman presented with anemia and normal renal function 1 year after a deceased-donor kidney transplantation for immunoglobulin A nephropathy-related end-stage renal disease. She received desensitization therapy, and 2 years later, she underwent transplantation with thymoglobulin induction. Despite repeated red cell transfusion and erythropoietin therapy, her anemia aggravated progressively. Bone marrow biopsy revealed normocytic normochromic PRCA. Real-time polymerase chain reaction detected a high plasma load of PVB19. Administration of intravenous immunoglobulin (IVIG) at 2 g/kg with adjuvant reduction of tacrolimus and discontinuation of myfortic acid effectively treated the anemia. However, the PVB19 load remained high, and PRCA recurred 7 months after the initial IVIG treatment. Tacrolimus was switched to cyclosporine in the second IVIG treatment, which successfully improved PRCA and reduced the PVB19 load. Our case suggested that PVB19-associated PRCA should be suspected when persistent anemia is observed in kidney transplant patients with heavy immunosuppression and that PVB19-associated PRCA can recur in the presence of persistent PVB19 viremia.

Refractory Anemia in a Kidney Transplant Recipient.

Anemia is a common finding after kidney transplantation (KT). Herein, we present a 34-year-old man who received a deceased-donor KT in 2017. Induction immunosuppression therapy consisted of thymoglobulin, tacrolimus (TAC) and methylprednisolone; the maintenance therapy included mycophenolate (MMF) 500 + 500 mg, TAC 4 + 4 mg and prednisolone (PD) 5 mg. One year after KT, he progressively developed dyspnea and fatigue. Laboratory exams revealed hypochromic microcytic anemia unresponsive to increasing doses of darbepoetin. Upper endoscopy and colonoscopy were normal. Bone marrow examination revealed erythroid hyperplasia with numerous proerythroblasts. Serology and viral load for human parvovirus B19 were both positive. Immunosuppression was reduced; he was treated with immunoglobulin. After one week, anemia improved. After 2 months the patient remained asymptomatic with stable hemoglobin. Although rare, PVB19 infection is a clinically significant infection that often presents as aplastic anemia in the post-transplantation period.

Parvovirus B19: What Is the Relevance in Transfusion Medicine?

Parvovirus B19 (B19V) has been discovered in 1975. The association with a disease was unclear in the first time after the discovery of B19V, but meanwhile, the usually droplet transmitted B19V is known as the infectious agent of the "fifth disease," a rather harmless children's illness. But B19V infects erythrocyte progenitor cells and thus, acute B19V infection in patients with a high erythrocyte turnover may lead to a life-threatening aplastic crisis, and acutely infected pregnant women can transmit B19V to their unborn child, resulting in a hydrops fetalis and fetal death. However, in many adults, B19V infection goes unnoticed and thus many blood donors donate blood despite the infection. The B19V infection does not impair the blood cell counts in healthy blood donors, but after the acute infection with extremely high DNA concentrations exceeding 1010 IU B19V DNA/ml plasma is resolved, B19V DNA persists in the plasma of blood donors at low levels for several years. That way, many consecutive donations that contain B19V DNA can be taken from a single donor, but the majority of blood products from donors with detectable B19V DNA seem not to be infectious for the recipients from several reasons: first, many recipients had undergone a B19V infection in the past and have formed protective antibodies. Second, B19V DNA concentration in the blood product is often too low to infect the recipient. Third, after the acute infection, the presence of B19V DNA in the donor is accompanied by presumably neutralizing antibodies which are protective also for the recipient of his blood products. Thus, transfusion-transmitted (TT-) B19V infections are very rarely reported. Moreover, in most blood donors, B19V DNA concentration is below 1,000 IU/ml plasma, and no TT-B19V infections have been found by such low-viremic donations. Cutoff for an assay for B19V DNA blood donor screening should, therefore, be approximately 1,000 IU/ml plasma, if a general screening of blood donors for single donation blood components is considered at all: for the overwhelming majority of transfusion recipients, B19V infection is not relevant as well as for the blood donors. B19V DNA screening of vulnerable patients after transfusion seems to be a more reasonable approach than general blood donor screening.

A Case Report of Parvovirus B19 Infection in a Renal Allograft.

Parvovirus B19 infection is undiagnosed in recipients undergoing solid organ transplantation. It is usually responsible for unexplained acute and chronic red blood cell aplasia that does not respond to erythropoietin therapy. Cases of parvovirus B19 infection associated with pancytopenia, solid organ dysfunction, and allograft rejection have been described in the literature. The deterioration of the immune system as a result of severe immunotherapy favors the reactivation of a previous infection or the acquisition of a new one. We present a case of a 32-year-old woman with a 1-year history of renal allograft transplant and previous cytomegalovirus (CMV) infection who presented with chest pain, polyarthritis, pancytopenia, and renal dysfunction. A serum sample using polymerase chain reaction showed a parvovirus titer of 13.8 trillion IU/mL and a CMV titer of 800 IU/mL. The renal biopsy revealed nucleomegaly with focal viral inclusions, along with changes associated with immunotherapy toxicity. Electron microscopy demonstrated capillary and tubular epithelial cells with "viral factories," thereby confirming the diagnosis. Thus, screening for parvovirus B19 is advised in high-risk patients who present with refractory anemia to avoid the complications of a chronic infection associated with the fatal rejection of the transplanted organ.

Double whammy- acute splenic sequestration crisis in patient with aplastic crisis due to acute parvovirus infection.

Splenic dysfunction is a major feature of sickle cell disease (SCD) and can manifest as acute splenic sequestration crisis (ASSC), which is the earliest life-threatening complication seen in patients with SCD. Aplastic crisis is another potentially deadly complication of sickle cell disease that develops when erythrocyte production temporarily drops. Infection with parvovirus B-19 frequently causes aplastic crises. These two complications are known to be mutually exclusive due to their classic presentation signs and symptoms but there have been few cases where a patient can have concomitant presentation of both phenomena, which can result in a fatal outcome. These few cases force us to rethink the etiology and subsequent management guidelines of these complications. We present to you a case of an unfortunate 23-year-old female who had both complications occurring at the same time, resulting in death.

[Intrauterine blood transfusion: Status report of 4years of practice in France (2011-2014)]. / Transfusions fœtales érythrocytaires : état des lieux sur 4 ans en France (2011­2014).

OBJECTIVES: The aim of our study was to evaluate in utero blood transfusion's (IUT) performed in France, among the French prenatal diagnosis centers in order to study the etiology of severe anemia requiring IUT. METHODS: We conducted a national retrospective descriptive study between 2011 and 2014. The data were collected using a survey sent by email to all French prenatal diagnosis centers. RESULTS: Among the 49 centers, 18 (38 %) had performed at least one IUT during the study period. The geographical repartition of these centers was appropriate for the "Aquitaine Pyrénées" region. Five centers performed 68 % of the national activity and one center performed 40 % the national activity. Each year, a mean of 204 IUTs were performed in 113 pregnancies. The principal etiology of severe fetal anemia requiring IUT was hemolytic disease of the fetus (69 % of the etiologies) with anti-RhD being the most prevalent antibody. The second etiology was represented by parvovirus B19 infection (17 % of IUTs). CONCLUSION: The French IUT activity was stable in numbers and indications during the study period. A national register could be set up in order to better evaluate prospectively the number of pregnancies concerned by IUT and to study the prevalence of hemolytic disease of the fetus due to anti-RhD antibodies.

Seroprevalence of parvovirus B19 antibodies and evidence of viremia among Nigerian patients with sickle cell anemia.

Clinical, biochemical and molecular evidence for the sickle cell anemia (SCA) crisis in Nigerian patients arising from parvovirus b19 infection remains inadequate. This study determined the prevalence and correlates of anti-parvovirus b19 antibodies in a population of SCA patients and non-SCA healthy controls in Lagos, Nigeria. In this prospective cross-sectional study, we enrolled 73 confirmed SCA patients from 5 district hospitals in Lagos and 81 sex and age-matched non-SCA healthy controls. Serum sample from each study participant was screened for anti-parvovirus b19 by ELISA and PCR techniques. Standard biomedical assays were also done. Anti-parvovirus b19 IgM and IgG antibodies were detected in 22 (14.3%) and 97 (62.9%) of the 154 sera screened, 13 (17.8%) and 45 (61.6%) in SCA patients; 9 (11.1%) and 52 (64.2%) in non-SCA controls. The overall seronegativity rate was 19.5%. Parvovirus B19 DNA was found in 2 (11.1%) of the 18 IgM seropositive SCA serum samples screened. On the whole, parvovirus b19 infection was more commonly asymptomatic in non-SCA controls but caused significant elevation in liver enzymes in infected SCA patients (P < 0.05). The risk of acute parvovirus b19 infection increased 65 times during unsteady state among the SCA patients. Although no deaths of infected patients were recorded during the study, age below 12 years, hospitalization and overcrowded environment were risk factors for infection. We conclude that parvovirus b19 is common in SCA patients, incurring greater susceptibility to infections.