Aplastic Crisis Research Articles

Erythema Infectiosum: A Narrative Review.

Erythema infectiosum occurs worldwide. School-aged children are most often affected. Since the diagnosis is mainly clinical, physicians should be well-versed in the clinical manifestations of erythema infectiosum to avoid misdiagnosis, unnecessary investigations, and mismanagement of the disease. The purpose of this article is to familiarize physicians with the wide spectrum of clinical manifestations and complications of erythema infectiosum associated with parvovirus B19 infection. A search was conducted in July 2022 in PubMed Clinical Queries using the key terms "Erythema infectiosum" OR "Fifth disease" OR "Slapped cheek disease" OR "Parvovirus B19". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. Erythema infectiosum is a common exanthematous illness of childhood caused by parvovirus B19. Parvovirus B19 spreads mainly by respiratory tract secretions and, to a lesser extent, the saliva of infected individuals. Children between 4 and 10 years of age are most often affected. The incubation period is usually 4 to 14 days. Prodromal symptoms are usually mild and consist of lowgrade fever, headache, malaise, and myalgia. The rash typically evolves in 3 stages. The initial stage is an erythematous rash on the cheeks, with a characteristic "slapped cheek" appearance. In the second stage, the rash spreads concurrently or quickly to the trunk, extremities, and buttocks as diffuse macular erythema. The rash tends to be more intense on extensor surfaces. The palms and soles are typically spared. Central clearing of the rash results in a characteristic lacy or reticulated appearance. The rash usually resolves spontaneously within three weeks without sequelae. The third stage is characterized by evanescence and recrudescence. In adults, the rash is less pronounced than that in children and is often atypical. Only approximately 20% of affected adults have an erythematous rash on the face. In adults, the rash is more frequently found on the legs, followed by the trunk, and arms. A reticulated or lacy erythema is noted in 80% of cases which helps to distinguish erythema infectiosum from other exanthems. Pruritus is noted in approximately 50% of cases. The diagnosis is mainly clinical. The many manifestations of parvovirus B19 infection can pose a diagnostic challenge even to the best diagnostician. Complications include arthritis, arthralgia, and transient aplastic crisis. In most cases, treatment is symptomatic and supportive. When parvovirus B19 infection occurs in pregnant women, hydrops fetalis becomes a real concern. Erythema infectiosum, the most common clinical manifestation of parvovirus B19 infection, is characterized by a "slapped cheek" appearance on the face and lacy exanthem on the trunk and extremities. Parvovirus B19 infection is associated with a wide spectrum of clinical manifestations. Physicians should be aware of potential complications and conditions associated with parvovirus B19 infection, especially in individuals who are immunocompromised, chronically anemic, or pregnant.

The Aplastic Crisis in HbSS: Observations from the Jamaican Birth Cohort

In order to document the prevalence, clinical features, hematology and outcome of the aplastic crisis in homozygous sickle cell disease (HbSS), a cohort study has been conducted from birth. Newborn screening of 100 000 deliveries at the main government maternity hospital, Kingston, Jamaica between 1973 and 1981 detected 311 cases of HbSS who have been followed at the Medical Research Council Laboratories at the University of the West Indies, Kingston, Jamaica. Clinically defined aplastic crises occurred in 118 (38%) patients at a median age of 7.5 years (range 0.5–23.0 years). All but one event seroconverted to parvovirus B19, the exception being a 9.3 year male with classic aplasia but subsequent IgG did not exceed 3 IU. Defined by zero reticulocyte counts, 94 patients presented with a median hemoglobin of 3.7 g/dL (range 18–87 g/L) representing a median fall from steady state levels of 3.8 g/dL. Clear epidemic peaks occurred at 1979–1980, 1984–1986, and 1990–1993 and the admission rate and use of blood cultures fell with each epidemic, reflecting increased familiarity with the complication. Symptoms were usually nonspecific and all but 7 were transfused. No patient had a recurrence and two died from aplasia (one with remote rural residence and the other following an incorrect diagnosis). Of those seroconverting to parvovirus B19, 68% manifested aplasia and 24% had no hematologic change. Correctly diagnosed and managed, the aplastic crisis is essentially benign. (230 words)

Clinical Presentations of Parvovirus B19: A Case Series.

Parvovirus B19 (PVB19) is a small, nonenveloped, single-stranded DNA virus commonly causing asymptomatic infections or mild, flu-like symptoms. In children, PVB19 can lead to various clinical conditions, including erythema infectiosum, arthropathy, transient aplastic crisis and papular-purpuric eruptions, among others. We present 3 pediatric cases treated at Luigi Sacco University Hospital in Milan, Italy, in March 2024, each demonstrating distinct manifestations of PVB19 infection. Case 1 involved a 7-year-old girl with a maculopapular rash and panniculitis-like symptoms. Case 2 described an 8-year-old boy with a maculopapular rash, vasculitis component and mild thrombocytopenia. Case 3 focused on a 7-year-old girl with petechial and purpuric eruptions and a mild decrease in platelets. Serological tests confirmed PVB19 infection in all cases. The discussed cases highlight the heterogeneous clinical spectrum of PVB19 infection and emphasize its potential to cause thrombocytopenia even in healthy children. The recent surge in PVB19 cases in Europe, aligned with known epidemiological cycles, underscores the importance of vigilance in diagnosis, particularly during peak seasons. Additionally, concerning the role of serological testing in the diagnostic process, the potential for cross-reactivity among viral antigens is pointed out. PVB19 is a common infection with a broad range of clinical presentations. Awareness of its potential complications, including thrombocytopenia, even in nonimmunocompromised children, is crucial. Moreover, understanding the epidemiological patterns of PVB19 can aid in anticipating and managing outbreaks, thus minimizing its impact on pediatric health.

Ensuring Transfusion Safety: Screening Blood Donors for Human Parvovirus B19.

Ensuring the safety of blood and blood products is a vital aspect of healthcare. The potential for transmission of pathogens through blood and blood products makes transfusion safety a significant concern. Despite advancements in testing methodologies, donated blood products still pose a risk for infection transmission. Human parvovirus B19 (B19V) is a small, single-stranded, non-enveloped DNA virus transmissible parenterally by blood transfusion. B19V causes a wide range of clinical manifestations, which is generally harmless in healthy individuals. B19V infection may cause severe complications, such as aplastic crises, as it affects erythrocyte progenitor cells in individuals with increased erythrocyte turnover. Additionally, B19V can be transmitted from pregnant women to their foetus, potentially causing hydrops fetalis and foetal death. The potential for transmission through blood and blood products makes B19V a significant concern for transfusion safety. In response to the growing recognition of B19V's impact on transfusion safety, various international health organisations have introduced guidelines to minimise its transmission through blood and plasma products. However, the implementation of these guidelines varies globally, with some regions, such as India, still lacking formal protocols for B19V monitoring. This review article explores the existing methodologies for screening blood donors for B19V, assesses the associated transfusion risks, and considers the implications for public health and clinical practice. By emphasising advancements in diagnostic techniques and the challenges of their implementation, this article provides a comprehensive overview of efforts to reduce the transmission of B19V through blood transfusions, thereby ensuring safer blood supplies and improved patient outcomes.

Prevalence, Risk Factors, and Complications of Sickle Cell Disease in Saudi Arabia: A Systematic Review.

This study examined sickle cell disease (SCD) in Saudi Arabia. A systematic search of relevant databases was conducted to identify studies investigating SCD in the Saudi population. Studies were then screened based on predefined criteria and critically appraised for methodological quality. Data was extracted and synthesized to provide an overall picture of the SCD burden in Saudi Arabia. The most commonly reported complications were vaso-occlusive crises (VOC), acute chest syndrome (ACS), acute painful crisis, splenic sequestration, osteomyelitis, aplastic crisis, hemolytic crisis, serious bacterial infections, chronic vascular occlusion (CVO), depression, sickle cell nephropathy (SCN), obstructive sleep apnea (OSA), and renal complications. Reduced blood levels of antioxidant trace elements (Cu, Zn, and Se) may encourage oxidative stress, which in turn may contribute to the pathophysiology of SCD. Infections and ACS were common among young children (<7 years) while pain attacks were common in older children (>7 years). The high rate of hospitalizations among SCD patients highlights the need for better management strategies. Future research should focus on understanding the underlying causes of SCD complications and developing new ways to control them.

Co-prevalence of Human Parvovirus 4 and Primate Erythroparvovirus 1 (B19) in Sickle Cell Disease and Healthy Populations

Background: Human Parvovirus 4 (P4) is a non-enveloped, single-stranded DNA virus belonging to the Tetraparvovirus genus within the Parvoviridae family. Epidemiologically, P4 exhibits similarities with its well-established family member, primate erythroparvovirus 1 (known as B19), a blood-borne virus implicated in causing aplastic crises in individuals with sickle cell disease (SCD). Despite the acknowledged association with B19, there is a dearth of prior investigations into the prevalence and clinical significance of P4 in SCD patients. Objectives: This study aims to ascertain the prevalence and outcomes of P4, along with exploring the co-prevalence of P4 with B19 in individuals with SCD. Methods: A total of 162 participants were enrolled, comprising 120 individuals with SCD and 45 healthy controls. The prevalence of P4 and B19 DNA was determined utilizing a nested-PCR method. Sequencing was performed on positive samples to validate the diagnosis, and a phylogenetic tree was constructed based on the sequencing results. Correlations in the data were analyzed using statistical methods. Results: The prevalence of P4 and B19, as well as the co-prevalence of these viruses, was significantly higher in SCD patients than in healthy individuals. Moreover, the prevalence of P4 did not exhibit a significant correlation with variables such as age, sex, aplastic crises, or specific complications associated with SCD. Conclusions: Sickle cell disease patients represent a susceptible population for P4 infection, as indicated by the heightened prevalence observed in this study.

When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms.

Aplastic anemia (AA) and hypoplastic myelodysplastic syndrome are paradigms of autoimmune hematopoietic failure (AHF). Myelodysplastic syndrome and acute myeloid leukemia are unequivocal myeloid neoplasms (MNs). Currently, AA is also known to be a clonal hematological disease. Genetic aberrations typically observed in MNs are detected in approximately one-third of AA patients. In AA patients harboring MN-related genetic aberrations, a poor response to immunosuppressive therapy (IST) and an increased risk of transformation to MNs occurring either naturally or after IST are predicted. Approximately 10%-15% of patients with severe AA transform the disease phenotype to MNs following IST, and in some patients, leukemic transformation emerges during or shortly after IST. Phenotypic transformations between AHF and MNs can occur reciprocally. A fraction of advanced MN patients experience an aplastic crisis during which leukemic blasts are repressed. The switch that shapes the disease phenotype is a change in the strength of extramedullary inflammation. Both AHF and MNs have an immune-active bone marrow (BM) environment (BME). In AHF patients, an inflamed BME can be evoked by infiltrated immune cells targeting neoplastic molecules, which contributes to the BM-specific autoimmune impairment. Autoimmune responses in AHF may represent an antileukemic mechanism, and inflammatory stressors strengthen antileukemic immunity, at least in a significant proportion of patients who have MN-related genetic aberrations. During active inflammatory episodes, normal and leukemic hematopoieses are suppressed, which leads to the occurrence of aplastic cytopenia and leukemic cell regression. The successful treatment of underlying infections mitigates inflammatory stress-related antileukemic activities and promotes the penetration of leukemic hematopoiesis. The effect of IST is similar to that of treating underlying infections. Investigating inflammatory stress-powered antileukemic immunity is highly important in theoretical studies and clinical practice, especially given the wide application of immune-activating agents and immune checkpoint inhibitors in the treatment of hematological neoplasms.

Identification of Risk Factors for Sickle Cell Crisis Readmissions: A Community Center Experience

Introduction: Sickle cell disease (SCD) exerts a significant morbidity and mortality burden worldwide, with 300,000 infants being diagnosed with SCD annually. The term sickle cell crisis (SCC) encompasses several acute conditions under its umbrella, namely vaso-occlusive crisis, aplastic crisis, splenic sequestration crisis, dactylitis, and acute chest syndrome. SCC has been established to be a known cause of readmissions across the year with studies showing 17% of the population returning two to three times annually. This has resulted in a high mean length of stay for this diagnosis (5.3 days) in comparison to an index hospitalization (4.9 days), with a mean cost of $8485 per admission. Readmissions owing to SCC have relayed a significant burden of 95,445 hospitalization days and a total charge of $609 million in the US. Despite the high morbidity and financial burden it imposes, limited studies have been performed studying the risk factors for readmissions in these patients. Despite the establishment of a framework of recommendations and guidelines, there appears to be a high incidence of readmissions and discrepancies in adherence to evidence based recommendations. We performed a retrospective study to evaluate the risk factors for patients hospitalized in three community hospitals between October 2021 and August 2022. Methods: The admissions database of a community health system across three hospitals was scanned for admissions with SCC between the time period October 2021 and August 2022. ICD9 and ICD-10 codes of SCC were used. 50 patients found with the admitting diagnosis code of SCC and 103 encounters were included. After excluding patients who left against medical advice before initiation of treatment, those with the wrong diagnosis and incomplete documentation, a cohort of 47 patients with 100 encounters was attained. Patient charts were reviewed and demographic variables such as age, gender and race were studied. Readmissions and the length of stay were assessed for risk factors with the help of a chi square test. Risk factors assessed included use of pain medications (opioids with non-steroid anti-inflammatory medications versus monotherapy), use of IV Fluid Boluses, placement of Hematology consult, having an established primary care physician and the use of hydroxyurea as a home medication. Results: 87% of the patient population was African American with equal gender distribution (Males 51%; Females 49%). 59% of the patient population lay in the age group of 18-35. 49% of the patient population was noted to have readmissions within the time frame studied with 29% of the patient population having a length of stay of more than 3 days. 100% of the patients without an established primary care physician (PCP) were noted to have readmissions in comparison to 3.6% of the patients with an established PCP (p&amp;lt; 0.01). Length of stay was less than 3 days for 91.3% of the patients treated with the combination of opioids and NSAID's for pain in comparison to 64.9% of the patients that were not treated with this combination (p= 0.014). It was noted however, that 37% of the population was on hydroxyurea outpatient and 44% of the cases had involved hematology for the inpatient management of these patients. IV Fluid boluses and their association with length of stays in our patient population was unequivocal. 52.7% of the patients on hydroxyurea had readmissions within 30 days as opposed to 28.6% of the patients not on the drug. This was likely explained by non-compliance to the medication. No deaths were reported in this patient cohort. Conclusion: Several risk factors for readmissions in SCC patients exist in the community setting. Our findings reported that lack of close outpatient follow up is associated with higher readmission rates. In addition, we also observed that the type of medical pain management (combination vs monotherapy) played a role in length of stay with combination therapy being linked to shorter hospitalization stay. Integrated education for various medicine specialties regarding management guidelines should be instituted. In addition, maximum utilization of social work and case management for ensuring close follow ups for this patient population may further mitigate readmissions of SCC patients in the community setting.

National Long-Term Follow-up of Children with Sickle Cell Disease Diagnosed By Newborn Screening in the Netherlands: Overview of the Morbidity and Mortality

Background: Sickle cell disease (SCD) is a genetic red blood cell disorder associated with increased morbidity and mortality. Newborn screening for SCD was introduced in January 2007 in the Netherlands to enable early diagnosis and initiation of preventive measures. The objective of this study was to assess the effect of newborn screening on the morbidity and mortality of children living with SCD in the Netherlands, 16 years after its implementation. Methods: In this national cohort study all children with SCD diagnosed by newborn screening were included. Patients were followed between 1 January 2007 and 31 March 2023 until end of follow-up, death or successful stem cell transplantation. Following informed consent, data were collected from medical files on SCD genotype, treatment, mortality and development of SCD-related complications. The incidence rate of SCD-complications was presented as lifetime-event per 100 person-years for the total duration of follow-up and for the age categories: 0-4, 5-11, and 12-16 years. Results: In total, 391 out of 540 eligible patients (72%) with SCD were included in all hospitals with patients with SCD under treatment, accounting for 3047 person-years. The mean age at the end of follow-up was 7.8 years (SD±4.5). The majority of patients had SCD genotype HbSS (58%), followed by HbSC (28%). As for the mortality, five patients died during follow-up, primarily at or below the age of 2 years (4/5, 80%). In three patients, the cause of death was related to SCD, including infection (n=2; aged 1.2 and 2.0 years) and acute splenic sequestration (n=1; 2.0 years). The SCD-related complications are presented in Table 1. The most common SCD complication in this cohort was vaso-occlusive crisis (including dactylitis) with hospitalization. SCD-related complications that mainly developed within the first 4 years of life, were vaso-occlusive crisis, acute hemolytic crisis, aplastic crisis, severe infections, splenic sequestration and ischemic cerebral infarction. Acute chest syndrome occurred equally in all age categories. Other SCD-related complications developed to a lesser extent in our cohort, and at a later age in adolescence or adulthood. Conclusion: In this cohort of neonatally screened children with SCD, a substantial number of SCD-complications occurred in the first 4 years of life. This study underlines the importance of parental education and 24/7 availably, high level acute specialized clinical care for these children from birth on. Further analysis to identify risk factors at young age for a severe phenotype will be conducted, to enable more targeted interventions in a timely manner. Hopefully, this will lead to reduction of disease burden, improving the quality of life in children living with SCD in the Netherlands.

Parvovirus in dermatology: A review

AbstractParvovirus B19 is a small nonenveloped single‐stranded DNA virus belonging to the parvoviridae family. The dermatological manifestations are varied ranging from infective to inflammatory, but the most common among infective etiologies is erythema infectiosum, also known as the fifth disease or ‘slapped cheek’ disease, which is mildly contagious. Clinical corroboration of symptoms and signs with serum antibody levels has been seen in acute and persistent parvoviral infections. Other dermatological manifestations of parvovirus B19 infections include erythema multiforme, vasculitis, reticular erythema, maculopapular eruptions, pustular eruptions, papular‐purpuric gloves and socks syndrome (PPGSS) and Gianotti‐Crosti syndrome. Skin lesions are quite characteristic and begin with oedema and erythema symmetrically localized to the hands and feet. Subsequently, petechial and purpuric changes appear varying from a few millimetres in diameter to larger, confluent patches. The primary target of parvovirus B19 is the hematopoietic‐erythroid cell line, specifically near the pronormoblast stage and the vulnerability to cellular damage increases along the differentiation lineage. There's multimodal clinical phenotypic presentation seen in parvoviral infections. Among the clinical expression of HPV B19 infections, the most common is dermatologic, however other manifestations such as rheumatologic and hematologic are not uncommon. However, some infections can be asymptomatic, especially in immunocompetent hosts, whereas in others with haematological abnormalities, these can lead to aplastic cellular crises.

Clinical Profiles of Children With Sickle Cell Anaemia Presenting With Acute Clinical Events: A Single-Center Study.

Sickle cell disease is a common genetic disorder characterised by chronic haemolytic anaemia and vaso-occlusive crisis. Sickle cell anaemia (SCA) has both short-term effects in the form of acute clinical events and long-term repercussions seen with chronic multiorgan involvement. It is associated with significant morbidity and mortality. In India, the disease is largely undocumented. Thus, there is an urgent need to highlight the features of the disease so that locally appropriate models of care may be implemented. This study aims to evaluate acute clinical events in SCA and to provide data that may help to reduce the rate of morbidity and mortality associated with this disease by early interventions. A cross-sectional observational study was conducted between November 2020 and May 2022 at Indira Gandhi Government Medical College and Hospital, Nagpur, Central India. The inclusion criteria included previously diagnosed patients of SCA (homozygous sickle cell disease) on high-performance liquid chromatography (HPLC) between the age groups of six months and 12 years, presenting with acute clinical events. The exclusion criteria included patients younger than six months and older than 12 years of age, and all patients with other haemoglobinopathies and sickle cell trait. The study was approved by the Institutional Ethical Committee. All the data was entered into a well-designed Microsoft Office Excel spreadsheet (v 2019, Microsoft, Washington, USA). All the clinical, biochemical, and haematological data were tabulated and analysed. A total of 100 children with sickle cell disease diagnosed by HPLC were enrolled during the study period. About 215 acute clinical events among the 100 cases were recorded, for which they were admitted to the paediatric ward or PICU. The majority (35%, n=35) were seen in the age group of six to nine years (school-going age). About 52% were male and 48% were female (male-to-female ratio= 1.08:1). Pain was the most common symptom. The highest incidence of 36.75% (n=79) was seen with acute painful crises and was the most common indication of hospitalisation, followed by acute febrile illness (AFI) (34.42%, n=74), aplastic crisis (10.23%, n=22), splenic sequestration crisis (9.77%, n=21), hepatobiliary involvement (3.72%, n=8), acute chest syndrome and haemolytic crisis (each 1.86%, n=4), and stroke (1.40%, n=3). In cases of having foetal haemoglobin (HbF) ≥20%, the incidence of acute painful crisis (p=0.0001), hand-foot syndrome (p=0.047), aplastic crisis (p=0.033), splenic sequestration crisis (p=0.039), and AFI (p=0.035) was low as compared to cases having HbF ≤20% which was statistically significant. The incidence of acute painful crisis, hand-foot syndrome, and an aplastic crisis was significantly low in patients receiving hydroxyurea therapy as compared to patients who were not on hydroxyurea. Out of 100 cases, four died during the study period, three died because of splenic sequestration crisis with septic shock, and one died due to hepatic encephalopathy due to haemolytic crisis with septic shock. Acute clinical events in sickle cell disease can have significant morbidity and mortality in the paediatric age group. The nutritional status of sickle cell disease children must be given due importance. Early initiation of hydroxyurea must be encouraged to maintain higher HbF levels, which plays a significant role in reducing morbidity.

Successful use of interferon alfa-2a for persistent parvovirus B19 infection.

Human infection with parvovirus B19 causes a range of clinical manifestations, including benign erythema infectiosum in children, arthralgias in adults, aplastic crisis in patients with bone marrow failure, and potentially fatal congenital hydrops fetalis. Persistent parvovirus B19 infection is a rare disease presentation mostly seen in adult women or immunocompromised individuals. Treatment options include corticosteroids and intravenous immunoglobulin; however, viral clearance is difficult to obtain and rarely maintained. In this Grand Round, we report the case of a 43-year-old man with persistent parvovirus B19 infection and anaemia, who was refractory to standard treatment regimens, and whom we successfully treated with pegylated interferon alfa-2a. Initial treatment led to viral clearance and remission of anaemia, although secondary recurrence of virus required treatment extension. Despite extensive genetic and immunological evaluations, no underlying primary or secondary immunodeficiency was identified in the patient. We propose interferon alfa-2a as a treatment option for persistent parvovirus B19 infection and advocate long-term follow-up of patients and potentially repeated treatment.

Parvo B19 and Anaemia: The Various Profiles – A Mini Review

Introduction: Parvovirus 19 (Parvo B19) is a single stranded DNA virus which predominantly affects school-aged children, parents of such children and adults who are working in day care centres or schools. Individuals with underlying haemoglobinopathies, haemophilia, immunocompromised, malignancy and pregnancy states are at a higher risk of infection. This virus has been associated with multiple clinical manifestations including erythema infectiosum, arthopathy, fetal cardiomyopathy and hydrops fetalis. However, one of the most significant complications is the anaemia caused in the adult population. This includes pure red cell aplasia and transient aplastic crisis (TAC). Review: Pure red cell aplasia occurs predominantly in patients with immunocompromised states. The aplasia characteristically presents with a chronic or recurrent severe normocytic normochromic anaemia with reticulocytopaenia. The bone marrow reveals an absence of red-cell precursors or with the presence of giant pro-normoblasts with intra-nuclear inclusions. The condition is effectively managed using packed red cell transfusions, based on the degree of anaemia, and with intravenous immunoglobulin at 1g/kg over a period of 2 days or, more preferably, 500mg/kg over 5 days. The majority of patients respond after 1-3 doses. Correction of the underlying patient risk factors is vital. TAC occurs more frequently in patients with underlying red-cell abnormalities. This presents with a one to two week severe anaemia with variable smear and cellular findings varying from microcytic hypochromic to normocytic normochromic. Additionally, there is a reduced reticulocyte percentage and index. Packed red cell transfusion and correction of the underlying risk factor are often sufficient for the management of anaemia. The addition of immunoglobulin administration, 500mg/kg over 5 days, may be needed for patients who are immunocompromised. Conclusion: Parvovirus B19 remains a prevalent and prominent virus associated with multiple medical conditions particularly in immunocompromised states such as that of HIV, as well as erythrocyte disorders. Clinically, the virus has a plethora of presentations, two of which are severe anaemias: transient aplastic crisis and pure red cell aplasia. These conditions may be effectively and successfully managed with intravenous packed red-cell transfusions, intravenous immunoglobulins and by addressing of the underlying patient risk factors.

A rare presentation of sickle cell disease diagnosed for the first time in a 60-year-old female: A misdiagnosis or missed diagnosis

Sickle cell disease (SCD) mainly manifests in early childhood. During the first 6 months of life, infants are largely protected by high levels of hemoglobin F; soon thereafter, the disease becomes evident in form of various crises such as vaso-occlusive crisis, hemolytic crisis, and acute chest syndrome, and in rare instances aplastic crisis. Therefore, the majority of patients with SCD are diagnosed in childhood or adulthood, whereas those with sickle cell trait usually remain asymptomatic. However, here, we are presenting a rare case in which a patient has been diagnosed to have SCD for the 1st time at the age of 60 years while being treated for dengue and severe anemia. Our case is one of the rare presentations of SCD, as she never required any blood transfusions even during childbirth and without any sickle crises; therefore, she might not be diagnosed with SCD till her presentation to our hospital. This indicates that advanced age should not be considered as an exclusion criterion for the suspecting and diagnosis of SCD. This case outlines the need for awareness and incorporation of screening for sickle cell anemia in childhood or adulthood as same thalassemia screening programs. The early diagnosis by screening programs will ensure appropriate treatment and therefore improve the quality of life in such patients.

Utility of Whole Exome Sequencing in the Early Diagnosis of Atypical Diamond-Blackfan Anemia.

Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome, with a hallmark of erythroblastopenia and congenital anomalies. DBA demonstrates genetic heterogeneity and variable phenotypic expression. We present two cases of atypical DBA harboring de novo mutations in the RPS-19 gene with c.49 G>C and c.357-1G>T allelic variants. The two cases presented confounding critical illness demonstrated by multiorgan failure, aplastic crisis, with case 2 meeting the criteria for hemophagocytic lymphohistiocytosis. We highlight the utility of genetic testing in the early diagnosis of DBA and the associated complexities and burden of disease in caring for DBA patients.

Human parvovirus B19-induced aplastic crisis in a patient with folate deficiency.

The authors declare no conflict of interest.

Molecular detection of human parvovirus B19 DNA amongst pregnant women attending antenatal clinic in Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria

Background: Parvovirus B19 infection causes a wide range of complication in pregnant women including spontaneous abortion, severe fetal anaemia, non-immune hydrops fetalis and even intrauterine fetal death, erythema infectiosum (5th) disease and aplastic crisis. Objective: To perform molecular detection of human Parvovirus B19 among pregnant women attending antenatal clinic in Nnamdi Azikiwe Teaching Hospital Nnewi, Anambra State, Nigeria. Materials and Methods: This is a cross-sectional study conducted among 92 consented pregnant women, between the ages of 20-40 years who are attending antenatal clinic in Nnamdi Azikiwe University Teaching Hospital Anambra State, Nigeria, from May 2020-November 2020. A total of 92 blood specimen was collected from the pregnant women. Result: Out of the 20 IgM positive samples analyzed for Parvovirus B19 DNA, 13(65.0%) had Parvovirus B19 DNA and 7(35.0%) were negative for Parvovirus B19 DNA. Prevalence of Parvovirus B19 DNA in relation to gestational age was highest (69.2%) among pregnant women who were in their 2nd trimester and the prevalence was lowest (0.0%) among pregnant women who were in their 3rd trimester. Prevalence of Parvovirus B19 in relation to history of blood transfusion was highest (100.0%) among pregnant women who have had transfusion history and the prevalence was lowest (0.0%) among pregnant women who had no transfusion history. Conclusion: The frequency rate of Parvovirus B19 DNA seropostivity was highest (65.0%) among the pregnant women investigated. The association of Parvovirus B19 DNA seroposivity with gestation age and history of blood transfusion was statistically significant.

An Overview of the Epidemiology, Pathogenesis, Diagnosis, and Treatment of Human Parvovirus B19

Human Parvovirus B19 (HPV-B19) infections are reported from different parts of the globe. The infection occurs in all age groups; however, most infections occur in childhood. There is evidence of exposure to the virus in about 80% of adults when screened for specific IgG. HPV-B19 is incriminated in several conditions like erythema infectious, aplastic crisis, hydrops fetalis and arthropathy. HPV-B19 is a cause of the Fifth disease (erythema infectious); it could also cause a febrile illness with or without rash in adults. Many adults especially women develop arthropathy and the condition could be chronic following a febrile illness. Patients (adults) with End Stage Renal Disease (ESRD) are prone to develop aplastic crisis or chronic anemia [1]. This review article aims to comprehensively describe the etiology, epidemiology, clinical features, diagnostic methods, and treatment in the management of HPV-B19.

Conjunctival tumour as an acute myeloblastic lymphoma presentation in a paediatric patient

AbstractPurpose: The most frequent ocular tumours are those that affect the conjunctiva which have a wide spectrum of presentation and can arise from any cell lineage that forms the conjunctiva, being the most representatives those that origins from epithelial and melanocytic cells. A case of a 10‐month‐old female patient who was diagnosed with acute myeloblastic leukaemia after studying a conjunctival tumour is presented.Methods: The case of a 10‐month‐old female with a conjunctival lesion located in the right eye who was also being studied for two masses, one on the right preauricular zone and the other on the left zygomatic area is described. About her medical history, she had an aplastic crisis due to parvovirus infection when she was 8 months old. No ophthalmological background was reported. On the clinical exam of the right eye, a pink conjunctival lesion located in the outer corner of the superior conjunctival fornix was found. The ocular motility was normal and the eyeball position was normal.Results: A biopsy of the conjunctival mass was performed immediately. The histopathology report showed infiltration with leukaemic cells. After this finding, a bone marrow biopsy, lumbar puncture, full‐body CT scan and an orbit MRI were performed, concluding the patient was suffering from an acute myeloblastic leukaemia with extramedullary involvement (face, orbit, ovaries) and central nervous system affection. After two cycles of chemotherapy, complete remission is achieved, including the conjunctival and orbital lesions.Conclusions: Haematology‐Oncology systemic diseases can imply the eye and the orbit. The manifestations most commonly found in children with leukaemia are proptosis, retinal and choroidal affection, optic nerve damage, and sixth nerve palsy. In the conjunctiva, it usually manifests as a subconjunctival salmon‐pink flesh coloured mass. Excision‐biopsy study is essential in the differential diagnosis of conjunctival neoplasms.

Effect of Hydroxyurea on Patient with High Fetal Hemoglobin Expression

High Fetal Hemoglobin (Hb F) expression in Sickle Cell Disease (SS), when first described, was defined as an "entirely benign disorder", due to its less severe manifestations; protective levels were described as 10 pg or more (AJCD, 133:1248, 1979). Continued high expression of Hb F as hereditary persistence of fetal hemoglobin (HPFH) occurs in 0.1% of African-American individuals. Other individuals may not have compound heterozygosity for Hemoglobin S and gene deletion HPFH but still have haplotypic differences resulting in higher HbF levels. We performed an IRB-approved chart review looking at SS patients with High HbF, followed at Children's Hospital from 2005-2020. We identified 13 children, 4-20 years, having mean HbF levels of 22.14 +/- 4.9%. Two children were considered inevaluable for analysis due to one being on voxelotor and the other being on chronic transfusion at the time of analysis. Of the 11 children remaining for analysis, 8 were girls and 3 boys. Complications requiring hospitalization included: acute chest syndrome, VOE, stroke including occult, osteomyelitis, aplastic crisis. Surgeries included osteotomy, cholecystectomy, and tonsillectomy/adenoidectomy. Eight children were placed on hydroxyurea (HU). After HU, total Hb and HbF did not significantly change (Hb 7.08+/-1.27 vs 8.97+/-1.55;HbF 22.4 +/-4.9 pre to 18.9+/-6.6, respectively). Admission or hospitalization frequency (admits or hospital stays/years studied) were evaluated, as were ED visits/years studied for SS-related problems. These data were: 1.36+/-0.51 pre vs. 0.4+/-0.46 post (for admits); 1.52+/-0.32 pre vs 0.33+/-0.21 post (for ED visits) p<0.05 for both). Three individuals were not on HU with an annual admission frequency of .75-1.2 and 1-3.2 for ED visits. The limitations of this study are: small n, lack of serologic proof of HU compliance, difficulties with data retrieval. Although the sample size is small, however, there does appear to be a salutary effect of HU on hospitalizations or vasoocclusive events after placement of these children on HU. Current recommendations to begin HU in children with SS at 9 months of age appear to have validation even in children with high HbF. We used the Kleihauer-Betke stain for HPFH diagnosis in most instances since gene analysis was not available to us due to insurance restraints; we acknowledge the need for genetic analysis to determine whether these individuals are "high F" or HPFH patients. Moderation of clinical course is dependent not only on HbF levels (which did not show significant increment after HU), but also on decreased WBC and platelet count with associated decreased inflammation and hypercoagulability.