Anorexia nervosa (AN) has a high mortality rate due to the widespread organ dysfunction caused by the underlying severe malnutrition. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases, while acute liver failure and aplastic crisis related to coagulation disease and encephalopathy rarely occur in AN patients. The supervised increase of caloric intake can quickly improve the elevated aminotransferases caused by starvation and aplastic crisis. This current case report describes a 12-year-old adolescent girl who was admitted with a 3-month history of weight loss. Within 3 months, she had lost 10 kg of weight. The girl was diagnosed with AN, acute liver failure, severe malnutrition with emaciation, electrolyte disorder, bradycardia and aplastic crisis. She was gradually supplemented with vitamins and enteral nutrition to avoid refeeding syndrome. After treatment, her liver function and haematopoietic function returned to normal. In conclusion, acute liver failure and aplastic crisis are rare but potentially life-threatening complications of AN, which could be improved by supervised feeding and timely rehydration. AN should be considered as the potential aetiology of acute liver failure and aplastic crisis.

BACKGROUND: Myelodysplastic syndrome (MDS) is caused by malignant proliferation and ineffective hematopoiesis. Oncogenic somatic mutations and increased apoptosis, necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells. An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage. Bone marrow cellularity and myeloblasts usually increase with disease progression. However, aplastic crisis occasionally occurs in advanced MDS.
METHODS: A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1 (MDS-EB-1) based on an increase in the percentages of myeloblasts and cluster of differentiation (CD)34+ hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples. The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years. In the treatment process, the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia. During the aplastic crisis, the bone marrow was infiltrated with sparsely distributed atypical lymphocytes. Surprisingly, the leukemic cells disappeared. Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3, CD5, CD8, CD16, CD56 and CD57, suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer (NK)/NKT cells that suppressed both normal and leukemic hematopoiesis. Elevated serum levels of inflammatory cytokines, including interleukin (IL)-6, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), confirmed the deranged type I immune responses. This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia. Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche. Antituberculosis treatment led to reversion of the aplastic crisis, disappearance of the atypical lymphocytes, increased marrow cellularity and 2 mo of hematological remission, providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis, the regression of leukemic cells and the activation of CD56+ atypical lymphocytes. Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state. However, the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.
CONCLUSIONS: Disseminated tuberculosis can induce CD56+ lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis, resulting in the development of aplastic crisis and leukemic cell regression.

Valproic acid (VPA) is a commonly used antiepileptic drug (AED). Aplastic crisis is defined as acute arrest of hematopoiesis. Stevens-Johnson syndrome (SJS) is a fatal cutaneous adverse drug reaction. We herein report a rare case of aplastic crisis and SJS in a single pediatric patient that were probably caused by VPA. A 2-year-old girl was involved in a car accident. She was diagnosed with skull fractures, cerebral contusions, pulmonary contusions, and fractures of the left iliac bone by computed tomography. VPA was administered as prophylaxis for post-traumatic epilepsy. From day 13, she developed repeated high fevers, and multiple antibiotics were ineffective; she was then transferred to our pediatric intensive care unit. After transfer, she developed liver function impairment, decreased peripheral blood cell counts, and skin damage. After withdrawal of the VPA and administration of prednisone, intravenous immunoglobulin, local skin care, and nutritional support, her body temperature normalized and her hematopoietic function and skin lesions successively resolved. She was transferred out of the pediatric intensive care unit on day 56 and discharged on day 70. At the 6-month follow-up, a blood examination was normal, and repeat computed tomography revealed multiple softening foci of the bilateral brain and less subdural effusion than before. To our knowledge, no report to date has described aplastic crisis and SJS in a single patient. The purpose of this paper is to increase clinicians\' knowledge in the treatment of adverse drug reactions (ADRs) and emphasize the importance of standardized application and strict monitoring of VPA in patients with post-traumatic brain trauma.

A toddler with an unbalanced diet and gastrointestinal bleeding by juvenile polyp developed an aplastic crisis due to the human parvovirus B19 (HPVB19). Although he exhibited microcytic anemia without iron deficiency in the acute phase of HPVB19 infection, he presented with iron deficiency anemia (IDA) in the chronic phase. IDA results in erythroblast hyperplasia and shortened red blood cell lifespan as like congenital hemolytic diseases, which may lead to an aplastic crisis during HPVB19 infection. It should be noted that iron deficiency is often masked, and microcytic anemia may be a clue for IDA.

Children with sickle cell disease (SCD) suffer life-threatening transient aplastic crisis (TAC) when infected with parvovirus B19. In utero, infection of healthy fetuses may result in anemia, hydrops, and death. Unfortunately, although promising vaccine candidates exist, no product has yet been licensed. One barrier to vaccine development has been the lack of a cost-effective, standardized parvovirus B19 neutralization assay. To fill this void, we evaluated the unique region of VP1 (VP1u), which contains prominent targets of neutralizing antibodies. We discovered an antigenic cross-reactivity between VP1 and VP2 that, at first, thwarted the development of a surrogate neutralization assay. We overcame the cross-reactivity by designing a mutated VP1u (VP1uAT) fragment. A new VP1uAT ELISA yielded results well correlated with neutralization (Spearman\'s correlation coefficient = 0.581; p = 0.001), superior to results from a standard clinical diagnostic ELISA or an ELISA with virus-like particles. Virus-specific antibodies from children with TAC, measured by the VP1uAT and neutralization assays, but not other assays, gradually increased from days 0 to 120 post-hospitalization. We propose that this novel and technically simple VP1uAT ELISA might now serve as a surrogate for the neutralization assay to support rapid development of a parvovirus B19 vaccine.

Parvovirus B19 infections are prevalent in children and commonly present as slapped cheek fever, also known as the fifth disease. They are seen frequently in daycares and professions that require close contact with children. The most common presentation is a rash that is prominent on the cheeks; less common symptoms include painful or swollen joints (polyarthopathy syndrome). The infection is self-limited and resolves within one to two weeks. The virus has an affinity to the red blood cell (RBC) precursors and can rarely cause temporary cessation of the bone marrow\'s RBC production, leading to aplastic anemia. This is especially of significance in patients predisposed to increased RBC destruction, such as hereditary spherocytosis, sickle cell anemia, and other morphological abnormalities of the RBC. The overlapping arrest of RBC production and excessive destruction leads to a transient aplastic crisis (TAC), leading to severe life-threatening anemia, requiring blood urgent blood transfusions. There have been many studies reporting the incidence of TAC in patients with sickle cell crisis. Only a few cases have been reported in patients with hereditary spherocytosis.

OBJECTIVE: The clinical presentations of parvovirus B19 in patients with underlying diseases have greater diversity than previously healthy patients. We retrospectively identified patients with polymerase chain reaction (PCR)-confirmed parvovirus B19 infection in attempt to describe its clinical features especially in these populations.
METHODS: From 2009 to 2018, patients with real-time PCR-confirmed parvovirus B19 infection were collected. Comparisons were done between previously healthy patients and patients with preexisting diseases, as well as patients with high (>5.5 × 105 copies/mL sera) and low viral loads.
RESULTS: Parvovirus B19 DNA was detected in 31 patients. Fourteen (45%) patients had underlying diseases, including six (19%) with immunologic diseases, five (16%) with hematologic diseases, and three (10%) with cardiopulmonary diseases. Only seven (23%) patients received an initial impression of erythema infectiosum prior to positive PCR. A higher proportion of patients with underlying diseases presented with fatigue and pallor, and suffered from tachycardia and hepatosplenomegaly compared to previously healthy patients. Among patients with a high viral load, a substantial proportion were of older age, suffered fatigue, and anemia. There was a trend of patients with immunologic comorbidity having a higher viral load.
CONCLUSIONS: The classical parvovirus B19 manifestations were less frequently observed in patients with a preexisting disease compared with previously healthy patients. Depending on host factors, the symptoms of parvovirus B19 infection can be multifaceted.

Introduction: Hyperhemolytic crisis is a rare and dangerous complication of sickle cell disease where the hemoglobin level drops rapidly. This can quickly lead to organ failure and death. In the literature, most cases of hyperhemolysis in sickle cell patients followed a red cell transfusion. Case Summary: In this article, we report a case of a 6-year-old African American boy with sickle cell disease who presented with fever, increased work of breathing, and consolidation in the left lower lobe of the lung on chest X-ray. He initially improved with oxygen, fluids, and antibiotics but his hemoglobin acutely dropped from 7.6 to 6 g/dL the next day of admission. He was not previously transfused, and his reticulocyte count remained high. Subsequent transfusion recovered his hemoglobin. Conclusion: This case demonstrates that in the background of the chronic hemolysis of sickle cell disease, an acute anemia should warrant exploration of aplastic crisis (parvovirus infection), immune hemolytic anemia, hepatic sequestration crisis, splenic sequestration crisis, and hyperhemolytic crisis as possible etiologies. Ongoing reticulocytosis and a source of infection may direct suspicion especially toward hyperhemolytic crisis even without preceding red cell transfusion. We propose that the optimum management should include full supportive care (including transfusions if necessary) and treatment of the underlying cause of hemolysis (such as infections or drug exposure).

OBJECTIVE: To determine whether patients with undiagnosed hereditary spherocytosis hospitalized for transfusions might have avoided hospitalization via earlier diagnosis.
METHODS: Charts of all (N = 30) patients with hereditary spherocytosis seen in pediatric hematology at West Virginia University-Charleston were reviewed. Family and transfusion history and presence of neonatal jaundice were recorded. Complete blood count and reticulocyte values during infancy were available for 20 of 30 patients, while baseline steady-state values were available for all 30.
RESULTS: Transfusions were given to 22 patients; 12 of 14 with an aplastic crisis were undiagnosed. In 10 of 12, the severity of anemia led to hospitalization (3 to intensive care). All 10 had prior mean corpuscular hemoglobin concentration and/or red cell distribution width elevations and a history of neonatal jaundice; 7 of 10 had a positive family history.
CONCLUSIONS: Undiagnosed hereditary spherocytosis may lead to inpatient transfusions for severe anemia. Earlier detection of hereditary spherocytosis is easily achievable and may reduce hospitalizations via closer monitoring.

Hemoglobin Evans is an unstable variant caused by a single nucleotide mutation that produces a valine-to-methionine substitution at residue 62 of the α-globin chain. It has not been reported in the Asian population and only three cases have been reported worldwide. We diagnosed a Japanese boy with chronic hemolytic anemia with hemoglobin Evans after genetic testing. This is the first familial case of hemoglobin Evans in an Asian population.