A coronavirus disease-2019 induced pancytopenia.

As the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) pandemic progresses, various hematologic complications have emerged, often centered around the hypercoagulable state. However, pancytopenia represents a rare but serious complication from SARS-CoV2 infection. While lymphopenia is a common finding, concomitant acute anemia and thrombocytopenia are not commonly reported. We describe a novel case of SARS-CoV2 pancytopenia in a 40-year-old male without active risk factors for cell line derangements but subsequent critical illness.

Parvovirus B19 infection masquerading as relapsed acute lymphoblastic leukaemia following haematopoietic stem cell transplantation.

A 7-year-old boy presented with a constellation of bone pain, a skeletal lesion, and pancytopenia after undergoing allogeneic haematopoietic stem cell transplantation for recurrent acute B-cell lymphoblastic leukaemia. Investigations to rule out leukaemia recurrence were unremarkable. Due to presence of maturation arrest in erythropoiesis with giant pronormoblasts and aberrant intranuclear inclusions on a bone marrow aspirate, parvovirus B19 (PVB-19) staining was completed and confirmed the diagnosis of disseminated PVB-19. Though PVB-19 infection after solid organ transplantation was reported in the literature as early as 1986, acquired PVB-19 viremia presenting with a solitary bone lesion is a novel presentation in paediatrics.

Hemophagocytic Syndrome as Uncommon Cause of Severe Pancytopenia After Liver Transplantation.

BACKGROUND: A rare but life-threatening cause of pancytopenia after liver transplantation is hemophagocytic syndrome. We present a 48-year-old woman who underwent liver transplantation and developed a hemophagocytic syndrome secondary to Epstein-Barr virus with a fatal course, despite initial treatment with immunosuppressants. The diagnosis was made based on the bone marrow aspiration, in which macrophages with phagocytic activity were observed, and clinical findings. Due to the very poor outcomes and high mortality, in patients with severe pancytopenia hemophagocytic syndrome should be excluded, and a bone marrow aspiration should be considered.

[A 79-year-old patient with pancytopenia and Kaposi sarcoma]. / Een 79-jarige man met pancytopenie en huidafwijkingen.

We report the case of a 79-year-old patient with pancytopenia and blue-purple cutaneous lesions on his legs, arms and in the oral cavity. These lesions had been present for several months. Based on a positive HIV test result we made a presumptive diagnosis of cutaneous Kaposi sarcoma. Histological examination confirmed the diagnosis of AIDS-related Kaposi sarcoma.

Parvoviral disease in childhood cancer: Clinical outcomes and impact on therapy at a tertiary cancer center in India.

BACKGROUND AND AIM: Parvovirus-B19 disease in immunocompromised children can cause myelosuppression and therapeutic delays. We studied the clinical profiles of children having symptoms suggestive of parvoviral disease at our institution, a large tertiary cancer center. METHODS: Children below age 15 years undergoing treatment for malignancies with clinical features suggestive of parvoviral infection, and/or unexplained drop in hemoglobin, and/or prolonged cytopenia were screened for parvovirus infection using DNA-PCR for parvovirus-B19 (PB19) in the peripheral blood. Patients testing positive from September 2014 till February 2017 were studied. RESULTS: Of the 59 patients (36 patients with hematolymphoid malignancies, 23 with solid tumors) screened for suspected parvoviral infections, 27 tested positive. Median age was 9.6 years (2.25-15 years), 18 (66%) had hematolymphoid malignancies, while 7 (33%) had solid tumors. Six patients (26%) were on intensive phases, 16 (60%) patients developed the symptoms during maintenance chemotherapy, and 4 (15%) after completion of therapy. Isolated anemia was the commonest feature seen in 10 patients (37%) while bicytopenia and pancytopenia were noticed in 8 (30%) and 9 (33%) patients respectively. Fifty percent of patients those who received rituximab (3/6) developed persistent parvoviremia (>4 weeks) as compared with 24% (5/21) of those who did not. Two patients (7%) developed hemophagocytic lymphohistiocytosis (HLH). Treatment delay by more than 14 days was encountered in a majority (62%), with 5 patients requiring treatment modification or even suspension. CONCLUSIONS: Parvoviral infection in children who are on or have recently completed chemotherapy can lead to multiple cytopenias and significant treatment delays. Rituximab exposure may lead to persistent parvoviral disease (p < 0.05). HLH, though occasional, can be a serious complication.

Azathioprine-induced pancytopenia with normal TPMT activity presenting with HSV oral ulcers.

A 65-year-old man with treatment-resistant psoriatic arthritis, hypertension, dyslipidaemia and benign prostatic hyperplasia (BPH) presented with herpes simplex virus (HSV) oral ulcers and a recent 15 lb weight loss due to reduced consumption. Five weeks previously, his methotrexate was tapered and he had begun taking azathioprine. The patient's thiopurine S-methyltransferase (TPMT) activity level was normal prior to starting azathioprine. He was found to have pancytopenia with normal folate levels and azathioprine was discontinued. His pancytopenia worsened, with a nadir 8 days after stopping azathioprine, before returning to normal levels. His oral ulcers improved and he was able to tolerate solid food. This case illustrates that decreased TPMT activity is not the only risk factor for pancytopenia as an adverse reaction to azathioprine. Furthermore, HSV stomatitis may be the presenting symptom of pancytopenia. The timeline of improvement in cell counts illustrated in this patient has implications for the management of suspected azathioprine-induced pancytopenia.

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.

Profile of HIV-Infected Hispanics with Pancytopenia.

Pancytopenia is seen in late HIV infection; it is associated with medical complications and with decreased survival. We determined the prevalence of pancytopenia at baseline in a cohort of HIV-positive Hispanics living in Puerto Rico, and compared their socio-demographic, immunological and clinical characteristics. A total of 1202 patients enrolled between 2000 and 2010 were included. They were grouped according to pancytopenia status, defined by having: platelets <150,000 µL, white cell count <4000 µL, and hemoglobin <12 g/dL (women) or <13 g/dL (men). Differences were evaluated using Student's t-test, Chi-square test and Kaplan-Meier method. The prevalence of pancytopenia was 8.7%. Patients with pancytopenia had lower BMI and lower CD4 count, as well as higher HIV viral load and higher proportions of unemployment, clinical AIDS and antiretroviral treatment (ART) use (p < 0.05). One-year mortality rate was significantly higher in patients with pancytopenia (18.1% vs. 5.1%, p < 0.001). When stratifying for ART this association persisted for patients who did not receive ART (41.4% vs. 5.2%, p < 0.001), but it was not seen in patients who received treatment (9.2% vs. 5.6%, p = 0.196). Pancytopenia was associated with elements of advanced stages of HIV. ART could reduce the mortality of HIV-patients with pancytopenia to levels comparable to patients without the disorders.

Cholestasis, ascites and pancytopenia in an immunocompetent adult with severe cytomegalovirus hepatitis.

Human cytomegalovirus (CMV) is a herpesvirus, which establishes lifelong latency after primary infection and leads to severe disease in immunocompromised patients. However, CMV infection in immunocompetent patients is usually asymptomatic and severe organ damage is rarely reported. We report a case of severe CMV hepatitis in an immunocompetent patient presenting with cholestasis, portal hypertension-related ascites and pancytopenia. The patient was asymptomatic with normal liver function and negative CMV DNA after two weeks of antiviral therapy. This case is an example of a common infection with an uncommon presentation, and suggests that testing for CMV should be carried out, even in patients with normal immune status, presenting with severe liver damage or cholestasis.

Fetal cytomegalovirus infection manifesting as transient pancytopenia.

We encountered a patient with a fetal cytomegalovirus infection manifesting as pancytopenia and thoracic hypoplasia. The fetal anemia was treated by transfusion via the umbilical cord, and did not progress after 22 weeks' gestation. The neutropenia resolved spontaneously, and only thrombocytopenia was persistent at birth. The severe thoracic hypoplasia led to pulmonary hypertension and required intensive postnatal respiratory management. Our experience suggests that pancytopenia is a possible manifestation in fetuses infected with cytomegalovirus. This may be transient, resolving spontaneously during fetal life; however, caution should be taken with blood counts, particularly platelet counts, after delivery. In addition, clinicians should carefully follow the thoracic volume in cytomegalovirus-infected fetuses and consider the possibility of postnatal severe respiratory insufficiency.

Systematic Epstein-Barr virus-positive T-cell lymphoproliferative disease presenting as a persistent fever and cough: a case report.

INTRODUCTION: Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is an extremely rare disorder and classically arises following primary acute or chronic active Epstein-Barr virus infection. It is characterized by clonal proliferation of Epstein-Barr virus-infected T-cells with an activated cytotoxic phenotype. This disease has a rapid clinical course and is more frequent in Asia and South America, with relatively few cases being reported in Western countries. The clinical and pathological features of the disease overlap with other conditions including infectious mononucleosis, chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis and natural killer cell malignancies. We describe the rare case of systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease in a 16-year-old Malay boy. CASE PRESENTATION: He presented with a six-month history of fever and cough, with pulmonary and mediastinal lymphadenopathy and severe pancytopenia. Medium- to large-sized, CD8+ and Epstein-Barr virus-encoded RNA-positive atypical lymphoid cells were present in the bone marrow aspirate. He subsequently developed fatal virus-associated hemophagocytic syndrome and died due to sepsis and multiorgan failure. CONCLUSIONS: Although systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is a disorder which is rarely encountered in clinical practice, our case report underlines the importance of a comprehensive diagnostic approach in the management of this disease. A high level of awareness of the disease throughout the diagnosis process for young patients who present with systemic illness and hemophagocytic syndrome may be of great help for the clinical diagnosis of this disease.

Pancytopenia secondary to cytomegalovirus reactivation.

A 64-year-old woman with a 1-year history of microscopic polyangiitis developed isolated pancytopenia secondary to cytomegalovirus (CMV) reactivation. The patient was originally admitted to the medical service for the management of a rapidly progressing 10 cm ulcer on her left lower extremity. Prior to admission, the patient had been on several immunosuppressive agents for the treatment of microscopic polyangiitis, including prednisone, azathioprine, cyclophosphamide and rituximab. Her hospital course was notable for pancytopenia and after a very thorough diagnostic work-up, the aetiology was found to be secondary to CMV reactivation. This was confirmed by blood analysis that revealed a highly elevated CMV level at 899 100 copies/mL by quantitative PCR. The patient was promptly treated with intravenous ganciclovir for a total course of 14 days before transitioning to an oral regimen. She had a pronounced response to the anti-CMV therapy with complete recovery of her white cell count, haemoglobin and platelet count to baseline.

Neonatal adenoviral infection: a seventeen year experience and review of the literature.

OBJECTIVES: To describe the clinical manifestations and short-term outcomes of adenoviral infections in neonates and review all published cases to better determine impact and treatment outcomes. STUDY DESIGN: Retrospective cohort study of all neonates hospitalized at Children's Medical Center (CMC) and Parkland Memorial Hospital (PMH), Dallas, TX with laboratory-confirmed adenoviral infection from January 1,1995-December 31, 2012. Neonates were identified by review of the CMC Virology Laboratory's prospective database of all positive adenovirus tests performed in the inpatient and ambulatory settings, and at PMH, of a prospective neonatal database that included all neonatal intensive care unit admissions. Patients also were identified by discharge International Classification of Disease, 9th edition codes for adenoviral infection. The medical records were reviewed, and a review of the English literature was performed. RESULTS: During 17 years, 26 neonates had adenoviral infection (25, CMC; 1, PMH). The principle reasons for hospitalization were respiratory signs (88%) and temperature instability (65%). Five (19%) had disseminated disease and 4 (80%) of these infants died. Ribavirin or cidofovir treatment, as well as immune globulin intravenous, did not improve outcomes except in 1 neonate. Literature review (n = 72) combined with our data found that disseminated infection was associated with death (68% vs 21% with localized infection, P < .001). In addition, neonates <14 days of age were more likely to have disseminated disease (44% vs 12%, P = .004) and death (48% vs 8%; P < .001). CONCLUSION: Adenoviral infection in hospitalized neonates was associated with severe morbidity and mortality, especially when infection was disseminated and involved the respiratory tract. Development of new therapeutic strategies is needed.

Calf-level factors associated with bovine neonatal pancytopenia--a multi-country case-control study.

Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A multi-country matched case-control study was conducted in 2011 to identify calf-level risk factors for BNP. 405 BNP cases were recruited from 330 farms in Belgium, France, Germany and the Netherlands by laboratory confirmation of farmer-reported cases. Up to four calves of similar age from the same farm were selected as controls (1154 calves). Risk factor data were collected by questionnaire. Multivariable modelling using conditional logistic regression indicated that PregSure®BVD (PregSure, Pfizer Animal Health) vaccination of the dam was strongly associated with BNP cases (adjusted matched Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval - ci 2.4, 134.4; p = 0.005), and second or more lactation PregSure-vaccinated dams were more likely to have a case than first lactation vaccinated dams (amOR 2.2 second lactation; ci 1.1, 4.3; p = 0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8; p = <0.001). Feeding colostrum from other cows was strongly associated with BNP if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; p = 0.012), but the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; p = 0.024). Feeding exclusively dam's milk was a higher risk than other types of milk (amOR 3.4; ci 1.6, 7.5; p = 0.002). The population attributable fractions were 0.84 (ci 0.68, 0.92) for PregSure vaccination, 0.13 (ci 0.06, 0.19) for feeding other cows' colostrum, and 0.15 (ci 0.08, 0.22) for feeding dam's milk. No other calf-level factors were identified, suggesting that there are other important factors that are outside the scope of this study, such as genetics, which explain why BNP develops in some PregSure-colostrum-exposed calves but not in others.

Monitoring the immune response to vaccination with an inactivated vaccine associated to bovine neonatal pancytopenia by deep sequencing transcriptome analysis in cattle.

Bovine neonatal pancytopenia (BNP) is a new fatal, alloimmune/alloantibody mediated disease of new-born calves induced by ingestion of colostrum from cows, which had been vaccinated with a specific vaccine against the Bovine Virus Diarrhoea Virus (BVDV). The hypothesis of pathogenic MHC class I molecules in the vaccine had been put up, but no formal proof of specific causal MHC class I alleles has been provided yet. However, the unique features of the vaccine obviously result in extremely high specific antibody titres in the vaccinated animals, but apparently also in further molecules inducing BNP. Thus, a comprehensive picture of the immune response to the vaccine is essential. Applying the novel approach of next generation RNA sequencing (RNAseq), our study provides a new holistic, comprehensive analysis of the blood transcriptome regulation after vaccination with the specific BVDV vaccine. Our RNAseq approach identified a novel cytokine-like gene in the bovine genome that is highly upregulated after vaccination. This gene has never been described before in any other species and might be specific to ruminant immune response. Furthermore, our data revealed a very coordinated immune response to double-stranded (ds) RNA or a dsRNA analogue after vaccination with the inactivated single-stranded (ss) RNA vaccine. This would suggest either a substantial contamination of the vaccine with dsRNA from host cells after virus culture or a dsRNA analogue applied to the vaccine. The first option would highlight the potential risks associated with virus culture on homologous cells during vaccine production; the latter option would emphasise the potential risks associated with immune stimulating adjuvants used in vaccine production.

Preemptive intravenous immunoglobulin allows safe and timely administration of antineoplastic therapies in patients with multiple myeloma and parvovirus B19 disease.

BACKGROUND: Parvovirus B19 (B19) disease is a rare cause of anemia in cancer patients and often goes unrecognized, causing delays in anticancer therapy. METHODS: A retrospective review was carried out of the records of patients with multiple myeloma who underwent melphalan-based autologous stem cell transplantation (MEL-ASCT) and developed B19 infection (January 2009-December 2011). Cases were defined by the presence of clinical and laboratory findings consistent with B19 disease in patients with repeatedly positive plasma quantitative polymerase chain reaction for parvovirus. RESULTS: Six patients qualified as cases; 5 presented with trilineage cytopenias (chronic in 1) and 1 with anemia later progressing to pancytopenia. Transfusion-dependent thrombocytopenia led to testing in 5 patients. Two of these patients also had manifestations of autoimmune disease. Therapy with intravenous immunoglobulin (IVIG) resulted in clinical and hematologic response in all; however, 1 patient, whose white blood cell counts and serum hemoglobin levels improved, required splenectomy for persistent thrombocytopenia. All patients required additional IVIG for recurrent B19 disease. Although viral load at diagnosis did not correlate with the severity of cytopenia, its decrease was associated with response during 17 of 20 evaluable episodes (P = 0.02). Preemptive IVIG allowed the safe administration of chemotherapy in 3 patients, including MEL-ASCT in 1. CONCLUSION: Parvovirus B19 can cause severe disease in myeloma patients including ASCT recipients. Thrombocytopenia - not anemia - was the leading presentation and may be associated with autoimmune conditions. Patients with unexplained cytopenias, particularly when prolonged, should undergo testing for circulating parvovirus. A reduction in viral load was associated with response to IVIG, although additional therapy was needed for recurrent disease. Most importantly, preemptive IVIG allowed for safe and timely administration of antineoplastic therapy in patients with ongoing B19 disease.