Intrauterine transfusion in 103 fetuses with severe anemia caused by parvovirus infection. A multicenter retrospective study.

PURPOSE: Evaluating procedure-related complications and perinatal outcomes after intrauterine transfusion (IUT) before or after 20+0 weeks of gestation in fetuses with severe anemia due to intrauterine human parvovirus B19 infection. METHODS: A retrospective study investigating fetuses requiring IUT for fetal Parvo B19 infection in two tertiary referral centers between December 2002 and December 2021. Procedure-related complications, intrauterine fetal death (IUFD), and perinatal outcome were correlated to gestational age (GA) at first IUT, the presence of hydrops and fetal blood sampling results. RESULTS: A total of 186 IUTs were performed in 103 fetuses. The median GA at first IUT was 19+3 (13+0-31+4) weeks of gestation. IUFD occurred in 16/103 fetuses (15.5%). Overall survival was 84.5% (87/103). Hydrops (p = 0.001), lower mean hemoglobin at first IUT (p = 0.001) and low platelets (p = 0.002) were strongly associated with IUFD. There was no difference observed in fetuses transfused before or after 20+0 weeks of gestation. CONCLUSION: IUT is a successful treatment option in fetuses affected by severe anemia due to parvovirus B19 infection in specialized centers. In experienced hands, IUT before 20 weeks is not related to worse perinatal outcome.

Parvovirus B19 myocarditis in children: a diagnostic and therapeutic approach.

Parvovirus B19 is one of the most frequent causes of pediatric myocarditis, associating high mortality rates or need for cardiac transplantation. The aim of this study is to describe the clinical course of Parvovirus B19 myocarditis in children with emphasis on the role of endomyocardial biopsy and cardiac magnetic resonance, and the use of an innovative therapeutic strategy. Eleven patients and 12 episodes of polymerase chain reaction (PCR)-confirmed Parvovirus B19 myocarditis were prospectively collected for 14 years. Diagnosis was confirmed either histopathologically or by magnetic resonance. A life-threatening clinical presentation is described, similar to previous series, but with 83.3% overall survival without transplantation. We also present a case of recurrent myocarditis, which is extraordinarily rare. Electrocardiographic patterns presented chiefly peaked p waves, low QRS voltages, and negative T waves on inferior or lateral leads. Endomyocardial biopsy is the gold standard diagnostic test; alternatively magnetic resonance could be a useful diagnostic tool. A good concordance between myocardial and blood PCRs was observed. Seven patients received treatment with corticosteroids and beta interferon and all underwent a significant cardiac function improvement. CONCLUSION: A severe clinical presentation is reported, similar to previous reports but with better outcomes. Endomyocardial biopsy is the gold standard diagnostic test; alternatively magnetic resonance may be used. Both blood and myocardium PCR can be used in children to establish the microbiological etiology. Steroids with IFNß could be a useful therapeutic option, although further multicenter studies are needed to confirm these results. WHAT IS KNOWN: • Parvovirus B19 is one of the most frequent causes of myocarditis in children. It is associated with a fulminant clinical presentation. • Endomyocardial biopsy is the gold standard diagnostic test but it is an invasive procedure. WHAT IS NEW: • Myocarditis may recur in pediatrics, even it is extraordinarily rare. • IFNß with steroids may be a useful therapeutic option to improve the outcomes.

Hemophagocytic lymphohistiocytosis associated with parvovirus B19-induced aplastic crisis in a hereditary spherocytosis patient: A case report and literature review.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation. It occurs because of severe inflammation due to uncontrolled proliferation of activated lymphocytes and histiocytes, characterized by the production of excessive levels of cytokines. Virus-associated HLH is a well-known entity, and parvovirus B19 is one of the common causes. Parvovirus B19 can also affect blood cell lineages. Therefore, HLH may be accompanied by several diseases such as cytopenia, aplastic anemia, and myelodysplastic syndrome. Herein, we report the case of a patient with hereditary spherocytosis who was diagnosed with parvovirus B19-induced HLH and aplastic crisis. A 7-year-old girl presented to our hospital with fever, pleural effusion, pancytopenia, hepatosplenomegaly, and hypotension. A bone marrow biopsy was performed under the suspicion of HLH, which revealed hemophagocytes. The diagnostic criteria for HLH were met, and prompt chemoimmunotherapy was initiated considering the clinically unstable situation. Her health improved rapidly after initiating treatment. Further study revealed that she had hereditary spherocytosis, and parvovirus B19 had caused aplastic crisis and HLH. The patient's clinical progress was excellent, and chemoimmunotherapy was reduced and discontinued at an early stage. This case shows that aplastic crisis and HLH can coexist with parvovirus B19 infection in patients with hereditary spherocytosis. Although the prognosis was good in this case of HLH caused by parvovirus B19, early detection and active treatment are essential.

Manufacturing and banking canine adipose-derived mesenchymal stem cells for veterinary clinical application.

BACKGROUND: Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications. RESULTS: After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. AD-MSCs presented normal karyotype, and did not form in vivo tumors. No adverse events were noted in the case treated with intravenously AD-MSCs. CONCLUSIONS: Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use.

[Treatment-refractory anaemia in a 35-year-old heart transplant recipient on chronic hemodialysis]. / Therapierefraktäre Anämie bei einem 35-jährigen Dialysepatienten nach Herztransplantation.

This article presents a case of pure red cell aplasia in a 35-year-old heart transplant recipient on chronic hemodialysis. Elevated parvovirus B19 immunoglobulin M blood levels were detected along with a high viral load of 80 billion IU/ml quantified by polymerase chain reaction. Bone marrow examination revealed giant proerythroblasts confirming parvovirus B19 infection. High-dose intravenous immunoglobulin was used for treatment. Anaemia had significantly improved 4 weeks later. Parvovirus B19 infection should be excluded in organ transplant recipients with anaemia due to ineffective erythropoiesis.

[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.

Identification and management of congenital parvovirus B19 infection.

Parvovirus B19 (B19V) infection is well known for its mild, self-limiting clinical presentations in children, such as erythema infectiosum. Approximately 40% of women of childbearing age are susceptible to B19V infection. While maternal B19V infection usually has a good prognosis, B19V can cause severe fetal anaemia and pregnancy loss due to its ability to suppress erythroid progenitor cells. Non-invasive ultrasound monitoring for fetal anaemia is usually performed if maternal seroconversion occurs in the first 20 weeks of gestation, with amniocentesis for fetal infection reserved for those who first present with fetal anaemia or hydrops of unknown cause. Intrauterine transfusion is the standard treatment for severe fetal anaemia and is associated with a significant improvement in survival. However, survivors of hydrops fetalis may have a higher rate of long-term neurodevelopmental complications compared with non-hydropic survivors. This review aims to synthesise published data on the diagnosis, surveillance and outcomes of congenital parvovirus infection to assist clinicians in diagnosing and managing this important condition.

Does an intrauterine exchange transfusion improve the fetal prognosis in parvovirus infection cases?

BACKGROUND: Almost 20% of parvovirus B19 foetal infections require intrauterine transfusions. In addition, myocardial dysfunction has been observed in severe parvovirus B19 infections. One objective of an intrauterine exchange transfusion (IUET) is to avoid an overload during the transfusion. Our aim was to study the obstetrical and neonatal outcomes in cases of IUETs performed for foetal parvovirus infections and to compare our survival rate to those studies in which simple in utero transfusions were chosen. STUDY DESIGN AND METHODS: This was a retrospective monocentre study of all patients followed up for parvovirus B19 infections in which IUETs were performed. An IUET was indicated when foetal hydrops was observed and/or when severe foetal anaemia was diagnosed though an elevation in the middle cerebral artery peak systolic velocity. The characteristics of each pregnancy and the neonatal outcomes were studied until hospital discharge. RESULTS: Thirty-five IUETs were performed in 26 foetuses. The median gestational age of the first IUET was 22.6 weeks. Only one foetal bradycardia incidence was recorded during the procedure. Three medical pregnancy terminations were observed in our series, secondary to severe cerebral anomalies confirmed in the magnetic resonance imaging. Five in utero deaths occurred, in which 2 of the foetuses underwent multiple IUETs. All the neonates had normal haemoglobin levels at birth, and none were transferred to the neonatal intensive care unit. The overall survival rate was 70%. CONCLUSION: IUETs exhibit a survival rate similar to that of simple intrauterine transfusions in foetal parvovirus infection cases.

Atraumatic splenic rupture following IVIg for parvovirus B19 pure red cell aplasia post renal transplant.

Parvovirus B19 (PB19) associated pure red cell aplasia (PRCA) is an uncommon but well described complication of immunosuppression post solid organ transplantation. We report a unique case of a renal transplant patient with PB19 associated PRCA who developed a spontaneous splenic rupture after receiving IVIg for persistent anemia. He subsequently required splenectomy. Within the spleen we subsequently identified PB19 affected cells.

Epidemiologic and Clinical Characteristics of Coronavirus and Bocavirus Respiratory Infections after Allogeneic Stem Cell Transplantation: A Prospective Single-Center Study.

Epidemiologic data about coronaviruses (CoVs) and human bocavirus (HBoV) in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are scarce. We conducted a prospective longitudinal study on respiratory viral infections (RVIs) in allo-HSCT recipients with respiratory symptoms from December 2013 until June 2016. Respiratory virus in upper and/or lower respiratory tract (URT and LRT) specimens were tested using Luminex xTAG RVP Fast v1 assay. Seventy-nine consecutive allo-HSCT recipients developed a total of 192 virologically documented RVI episodes over 30 months. The median follow-up after RVI was 388 days (range, 5 to 923). CoV or HBoV was detected in 27 of 192 episodes (14%); 18 of 79 recipients (23%) developed a total of 21 CoV RVI episodes, whereas 6 recipients (8%) had 1 HBoV RVI episode each. Fourteen CoV RVI episodes were limited to the URT, whereas 7 affected the LRT. Co-pathogens were detected in 8 (38%) CoV cases. Type OC43 CoV was the dominant type (48%) followed by NL63 (24%), KHU1 (19%), and 229E (9%); the CoV hospitalization rate was 19%, whereas mortality was 5% (1 patient without any other microbiologic documentation). Among the 6 recipients with HBoV (3%), only 1 had LRT involvement and no one died from respiratory failure. In 5 cases (83%) HBoV was detected along with other viral co-pathogens. CoV RVIs are common after allo-HSCT, and in a significant proportion of cases CoV progressed to LRT and showed moderate to severe clinical features. In contrast, HBoV RVIs were rare and mostly presented in the context of co-infections.

Parvovirus B19-associated Hemophagocytic Lymphohistiocytosis in a Patient With Glucose-6-phosphate Dehydrogenase Deficiency.

We report a case of a 12-year-old male with glucose-6-phosphate dehydrogenase deficiency presenting with clinical signs of sepsis and pancytopenia. Investigations revealed parvovirus B19 (PVB19)-associated hemophagocytic lymphohistiocytosis (HLH). The patient recovered fully and quickly with symptomatic treatment. Current evidence suggests that PVB19-associated HLH has a favorable prognosis. Mild undiagnosed cases of HLH may be the cause of pancytopenia in PVB19 infections.

Early Intrauterine Transfusion in Fetuses with Severe Anemia Caused by Parvovirus B19 Infection.

OBJECTIVE: To describe procedure-related complications and perinatal survival after intrauterine transfusion (IUT) before 20 weeks of gestation in fetuses with severe anemia due to human parvovirus B19 infection. MATERIALS AND METHODS: A retrospective study was conducted of all fetuses requiring IUT before 20 weeks of gestation in two tertiary referral centers between January 2002 and July 2015. Gestational age (GA) at first IUT, fetal blood sampling results, and presence of hydrops were related to procedure-related complications, fetal death (FD), and perinatal outcome. RESULTS: A total of 93 IUTs was performed on 55 fetuses. The mean GA at first IUT was 16+6 (13+0-19+6) weeks. FD occurred in 11 (20.0%) of the 55 fetuses. Overall survival was 80.0% (44/55). Hydrops was present in 38.2% (21/55) and was strongly associated with FD (p = 0.001). There was no difference with regard to FD, hydrops, or hemoglobin concentration at first IUT in fetuses with transfusion before or after 16+0 weeks. CONCLUSION: Severe anemia due to parvovirus B19 infection in the early second trimester can be treated successfully by IUT before 20 weeks of gestation in specialized centers with sufficient expertise.

Persistent symptomatic parvovirus B19 infection with severe thrombocytopenia transmitted by red blood cell transfusion containing low parvovirus B19 DNA levels.

BACKGROUND: Transfusion-mediated human parvovirus B19 (PVB19) infection is rare but often causes severe hematologic disorders. In Japan, routine blood donor screening for PVB19 antigen (detection sensitivity, 106.4 IU/mL) using a chemiluminescent enzyme immunoassay (CLEIA) was introduced in 2008. However, there is no consensus on the minimal infectious dose of PVB19 permissible for red blood cells (RBCs). CASE REPORT: A 64-year-old man, who had received hemodialysis for diabetic nephropathy for 5 years, underwent an RBC transfusion for anemia caused by hemorrhagic enterocolitis. He developed persistent high fever and progressive thrombocytopenia. He was diagnosed with PVB19 infection when a marrow examination showed giant erythroblasts, and his serum was positive for PVB19 DNA. His serum was negative for PVB19 immunoglobulin (Ig)M and IgG before transfusion, but positive for both after transfusion. This PVB19 infection was deemed to be transmitted by the RBC transfusion because low levels of PVB19 DNA (1.10 × 104 IU/mL) were detected in one of the blood donors. A DNA homology test of PVB19 showed complete genomic identity between the virus in the donor and our patient. CONCLUSION: We report a patient who developed persistent PVB19 infection from an RBC transfusion containing low levels of PVB19. This is the second case of transfusion-mediated PVB19 infection since the introduction of CLEIA in 2008. Transmission may occur in immunocompromised patients lacking PVB19-neutralizing antibodies. The report of further such cases will allow the establishment of minimal threshold values and more effective screening tests for PBV19 transmission through RBC products.

Neonatal outcome after fetal anemia managed by intrauterine transfusion.

UNLABELLED: In-utero transfusion is now well under control and improves the survival of foetuses monitored for fetal anemia with a survival rate of more than 80 %. The aim was to evaluate short-term neonatal outcome after fetal severe anemia managed by intrauterine transfusions. We did a retrospective study of all neonates born after management of severe fetal anemia (n = 93) between January 1999 and January 2013 in our regional center. The two main causes of anemia were maternal red blood cell alloimmunization (N = 81, 87 %) and Parvovirus B19 infection (N = 10, 10.8 %). In the alloimmunization group, phototherapy was implemented in 85.2 % of cases with a maximum level of bilirubin of 114.4 ± 60.7 (mg/dl). Transfusion and exchange transfusion were, respectively, required in 51.9 % and in 34.6 % of cases. One neonate presented a convulsive episode, and we observed three neonatal deaths. In the parvovirus group, none of the child had anemia at birth and no management was necessary. CONCLUSION: Contemporary management of Rhesus disease is associated with encouraging neonatal outcomes. In case of Parvovirus infection, no specific management is necessary at. But, in all cases of fetal anemia, children should be followed up with particular attention to neurologic development. WHAT IS KNOWN: • In-utero transfusion is now well under control and improves the survival of fetuses monitored for fetal anemia. • Limited studies are available on the effect of IUT on postnatal outcome in infants with a history of fetal anemia. What is New: • Contemporary management of severe Rhesus disease is associated with encouraging neonatal outcomes. • The majority of infants can be managed with phototherapy and a limited number of top-up transfusions and exchange transfusions. In case of Parvovirus infection, the short-term neonatal outcome is excellent.

Non-immune Hydrops fetalis due to Parvovirus B19 Infection in 2 Extremely Preterm Infants: Perinatal Management and Long-term Neurodevelopmental Outcome.

Parvovirus B19 (B19V) infection during pregnancy can lead to fetal damage and even fetal loss. In some cases a severe fetal anemia with hydrops fetalis occurs. An intrauterine red blood cell transfusion can reduce the mortality rate. Neurodevelopmental outcome after fetal B19V infection is affected by fetal anemia and presumably direct infection of the CNS. There are only a few studies on long-term neurodevelopmental outcome after B19V infection induced hydrops fetalis. There are hardly any long-term data especially in preterm infants. We report on the long-term outcomes of 2 extremely preterm children after non-immune hydrops fetalis due to intrauterine B19V Infection.

Clinical presentation and outcome of 20 fetuses with parvovirus B19 infection complicated by severe anemia and/or fetal hydrops.

AIM: The aim of this study was to assess the prognosis of parvovirus B19 infection with severely anemic and/or hydropic fetuses according to initial ultrasound and biological criteria. MATERIAL AND METHODS: Retrospective study of 20 cases of congenital parvovirus B19-proven infection (positive PCR) complicated by fetal anemia and/or hydrops was examined. Anemia was suspected on an elevated peak systolic velocity of the middle cerebral artery and was confirmed by fetal blood sampling. RESULTS: Survival rate was 70% (14/20) overall and 76% (13/17) for fetuses with one or more transfusions. When fetal effusion regressed after the transfusion, all 11 fetuses survived, and neonatal condition was favorable for all. Among the 14 live-born children, there was one neonatal death and one admission to the neonatal care unit with no major complications. CONCLUSION: Despite active management by transfusion in fetuses with parvovirus B19 infection, mortality remained substantial during the acute phase of anemia and fetal hydrops. Regression of effusion appears to be an important variable for prognosis. Non-anemic forms exist with isolated refractory ascites or pleural effusion. Maternal mirror syndrome appears to reflect the intensity and persistence of the fetal anemia.

Intrauterine blood transfusion: current indications and associated risks.

Fetal anemia is a serious complication in pregnancy and associated with perinatal mortality and morbidity. During 25 years of worldwide experience with intravascular intrauterine blood transfusion, a variety of indications have been described. Intrauterine transfusion (IUT) treatment is considered most successful for fetal anemia due to red cell alloimmunization. Moreover, the use of this procedure has also been reported in pregnancies with parvovirus B19 infection, fetomaternal hemorrhage and placental chorioangiomas, for example. This review focuses on the current indications of intrauterine blood transfusions. In addition, we describe the potential complications of IUT treatment.

TCRαß-depleted hematopoietic stem cell transplant and third-party CD45RA+ depleted adoptive cell therapy for treatment of post-transplant parvovirus B19 aplastic crisis.

This is a case report of a 6-year-old girl with relapsed B cell acute lymphoblastic leukemia in which adoptive cell therapy was applied successfully to treat refractory human parvovirus (HPV) B19 infection. Allogenic chimeric antigen receptor (CAR) T-cell therapy (bispecific CD19/CD22) was bridged to hematopoietic stem cell transplantation (HSCT) using a haploidentical paternal donor. However, HPV B19 DNAemia progressed and transfusion-related graft versus host disease occurred. After finding a third-party related donor with a better HLA match, haploidentical HPV B19-seropositive CD45RA+ depleted cells (16.5 × 106/kg) were administered and paternal TCRαß+ depleted stem cell were retransplanted. The HPV B19 DNAemia became negative within 1 week and the reticulocyte, neutrophil, hemoglobin, and platelet counts gradually normalized. The patient remained stable during the 1-year outpatient follow-up period. Thus, our case report highlights that persistent B19 infection can lead to pancytopenia, aplastic crisis, and graft rejection and TCRαß+ depleted haplo-HSCT is an effective means of hematopoiesis recovery. CD45RO memory T-cell therapy is the key to treating and preventing the development of refractory severe HPV B19 infection.