Epstein-Barr virus (EBV) causes various acute and chronic diseases. Chronic active EBV infection (CAEBV) is characterized by infectious mononucleosis-like symptoms that persist for more than 6 months with high viral loads in peripheral blood and/or an unusual pattern of anti-EBV antibodies. Severe CAEBV is associated with poor prognosis with severe symptoms, an extremely high EBV-related antibody titer, and hematologic complications that often include hemophagocytic lymphohistiocytosis. However, CAEBV which led to the development of aplastic anemia (AA) has not been reported yet. A 73-year-old woman was admitted to our hospital with intermittent fever, general weakness and elevated liver enzymes. In the serologic test, EBV-related antibody titer was elevated, and real-time quantitative-PCR in peripheral blood showed viral loads exceeding 10(4) copies/microg DNA. Liver biopsy showed characteristic histopathological changes of EBV hepatitis and in situ hybridization with EBV-encoded RNA-1 was positive for EBV. Pancytopenia was detected in peripheral blood, and the bone marrow aspiration biopsy showed hypocellularity with replacement by adipocytes. AA progressed and the patient was treated with prednisolone but deceased 8 months after the diagnosis due to multiple organ failure and opportunistic infection. Herein, we report a rare case of severe CAEBV in an adult patient accompanied by AA and persistent hepatitis.
Aged ; Anemia, Aplastic/*complications ; Carbapenems/therapeutic use ; Chronic Disease ; DNA, Viral/blood ; Epstein-Barr Virus Infections/complications/*diagnosis/pathology ; Female ; Hepatitis/*complications ; Herpesvirus 4, Human/*genetics/isolation & purification ; Humans ; Real-Time Polymerase Chain Reaction ; Severity of Illness Index ; Urinary Tract Infections/drug therapy

No abstract available.
Adolescent ; Anemia, Aplastic/*diagnosis/pathology ; Bone Marrow/pathology ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Half-Life ; Humans ; Immunohistochemistry ; Male ; Mutation ; Myelodysplastic Syndromes/*diagnosis/pathology ; Retrospective Studies ; Tumor Suppressor Protein p53/genetics/*metabolism

OBJECTIVETo analyze changes in gene amplification in the mitochondrial genome and in the ID4 gene promoter methylation region in patients with chronic aplastic anemia (CAA) suffering from Kidney (Shen) yin deficiency or Kidney yang deficiency.

METHODSBone marrow and oral epithelium samples were collected from CAA patients with Kidney yin deficiency or Kidney yang deficiency (20 cases). Bone marrow samples were collected from 20 healthy volunteers. The mitochondrial genome was amplified by polymerase chain reaction (PCR), and PCR products were used for sequencing and analysis.

RESULTSHigher mutational rates were observed in the ND1-2, ND4-6, and CYTB genes in CAA patients suffering from Kidney yin deficiency. Moreover, the ID4 gene was unmethylated in bone marrow samples from healthy individuals, but was methylated in some CAA patients suffering from Kidney yin deficiency (positive rate, 60%) and Kidney yang deficiency (positive rate, 55%).

CONCLUSIONSThese data supported that gene mutations can alter the expression of respiratory chain enzyme complexes in CAA patients, resulting in energy metabolism impairment and promoting the physiological and pathological processes of hematopoietic failure. Functional impairment of the mitochondrial respiration chain induced by gene mutation may be an important reason for hematopoietic failure in patients with CAA. This change is closely related to maternal inheritance and Kidney yin deficiency. Finally, these data supported the assertion that it is easy to treat disease in patients suffering from yang deficiency and difficult to treat disease in patients suffering from yin deficiency.

Adult ; Anemia, Aplastic ; genetics ; Base Sequence ; Biopsy ; Bone Marrow ; pathology ; Case-Control Studies ; Child ; Chronic Disease ; DNA Methylation ; genetics ; DNA, Mitochondrial ; genetics ; Electrophoresis, Agar Gel ; Female ; Genome, Mitochondrial ; genetics ; Humans ; Inhibitor of Differentiation Proteins ; genetics ; Kidney ; pathology ; Male ; Middle Aged ; Mutation ; genetics ; Polymorphism, Genetic ; Promoter Regions, Genetic ; genetics ; Yin Deficiency ; genetics ; Young Adult

OBJECTIVETo explore the clinical characteristics, and the effect of paroxysmal nocturnal hemoglobinuria (PNH) clone size and its evolution on response and survival in aplastic anemia (AA) patients.

METHODSThe clinical data of 90 AA cases with PNH clones from 316 AA patients between January 2011 and September 2014 were retrospectively reviewed, their clinical characteristics were analyzed, and the influence of PNH clone evolution and size on response and survival were explored.

RESULTS① Of 316 patients, 90 cases (28.5%) with PNH clones. Of 83 cases with long-term follow-up data available, the complete (CR) and partial response (PR) rates were 43.4% and 33.7% respectively, with the overall responsive rate of 77.1%. The 3-year and 5-year overall survival (OS)rates were 79.4% and 76.1% respectively. ② After immunosuppressive therapy (IST), the PNH clone changed from negative to positive in 24 cases, persistently positive PNH clones were observed in 22 cases, disappeared in 10 cases. There were no significant differences in terms of overall responsive rates, survival rates, absolute reticulocyte value, TBIL, IBIL and LDH among the three groups (P >0.05). Ten cases became AA-PNH after a median time of 15.6 months, no significant differences were found in overall responsive and survival rates between the 10 cases and the other 46 cases who were monitored for PNH clones (P values were 0.896, 0.688, respectively). ③ According to univariate analysis, age≥55, infection, VSAA, ANC <0.5 × 10(9)/L and absolute reticulocyte value <0.012 × 10(12)/L had significant influence on survival (P values were 0.026, 0.000, 0.001, 0.000 and 0.010, respectively). Cox regression model analysis identified that age, infection and ANC were independent prognostic factors affecting survival (P values were 0.050, 0.012 and 0.050, respectively). The PNH clone size had no significant influence on response and survival based on univariate and Cox analyses.

CONCLUSIONThe PNH clone size and its evolution had no significant influence on response and survival.

Anemia, Aplastic ; complications ; pathology ; Clone Cells ; Hemoglobinuria, Paroxysmal ; complications ; pathology ; Humans ; Immunosuppression ; Reticulocytes ; Retrospective Studies

BACKGROUND: The presence of significant dysplasia in bone marrow (BM) aspirates helps to distinguish between hypocellular myelodysplastic syndrome (hMDS) and aplastic anemia (AA). Occasionally, diluted BM aspirates make it difficult to recognize dysplastic changes and can also negatively affect the detection of cytogenetic abnormalities in hMDS. We evaluated the usefulness of CD34 and p53 immunoreactivity for discriminating between hMDS and AA and for estimating survival outcomes in hMDS patients. METHODS: BM clot section (BMC) or BM biopsy (BMB) specimens were obtained from 64 hMDS/AA patients (33 with hMDS and 31 with AA) and seven controls. Immunohistochemical (IHC) staining for CD34 and p53 was performed by using the EnVision detection system (Dako, Denmark). We compared the results of IHC staining, BM findings, and chromosomal analyses, and determined overall survival outcomes. RESULTS: The number of CD34- and p53-positive BM cells was higher among the patients with hMDS than among the patients with AA (P<0.001 and P=0.001, respectively). hMDS patients with increased CD34-positive cells had significantly poorer survival outcomes compared with those with normal number of CD34-positive cells (P=0.013). CONCLUSIONS: CD34 and p53 IHC stains of BMC or BMB provide useful information for differentiating between hMDS and AA. CD34 IHC staining of BMC or BMB also provides useful information for estimating survival outcomes in hMDS patients.
Adolescent ; Adult ; Anemia, Aplastic/*diagnosis ; Antigens, CD34/*metabolism ; Bone Marrow/metabolism/*pathology ; Child ; Chromosome Aberrations ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Myelodysplastic Syndromes/*diagnosis/mortality ; ROC Curve ; Tumor Suppressor Protein p53/*metabolism

OBJECTIVETo explore the clinical characteristics and histopathological morphology features of bone marrow biopsies between refractory cytopenia of children (RCC) and acquired aplastic anemia (AAA) to facilitate the diagnosis, differential diagnosis and treatment of RCC and AAA.

METHODSWe retrospectively analyzed clinical data and histopathological morphology of bone marrow biopsies in RCC or AAA patients referred to our hospital from January 2011 to December 2012.

RESULTSThere were totally 130 patients studied. The final diagnoses of them were RCC in 78 cases (60.0%) and AAA in 52 cases (40.0%). The median WBC count, absolute neutrophil count, blood platelet count, hemoglobin level, and reticulocyte count were all higher in RCC children than AAA (P<0.01). All of RCC patients showed hypocellular biopsy specimens, and 84.6% (66/78) of them had cellularity of bone marrow biopsy specimens ranging from 20% to 60%. Patchy pattern distribution was seen in 98.7% (77/78) of RCC cases, and micromegakaryocyte was found in 61.5% (48/78) of RCC cases. All of AAA patients showed severe hypocellular biopsy specimens, and 88.5% (46/52) of them had cellularity of bone marrow biopsy specimens under 5%. Megakaryocyte was not found in 98.1% (51/52) of AAA cases. The response rates of immunosuppressive therapy using CsA ± rabbit anti- thymocyte globulin ± androgen ± traditional Chinese medicine for patients with RCC and AAA were 59.5% and 26.9% at 3 months (P=0.011), and 75.0% and 38.1% at 6 months, respectively (P=0.007).

CONCLUSIONRCC patients showed milder cytopenia and bone marrow hyperplasia than AAA. Patchy distribution of hematopoietic cells, erythroid islands with a marked left shift and micromegakaryocytes were decisive histomorphological patterns used to separate RCC from SAA. Immunosuppressive therapy using CsA ± rabbit anti- thymocyte globulin ± androgen ± traditional chinese medicine was an effective therapy in patients with RCC and AAA, and the outcome of immunosuppressive therapy for RCC patients was superior to that of AAA patients.

Adolescent ; Anemia, Aplastic ; diagnosis ; pathology ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Myelodysplastic Syndromes ; diagnosis ; pathology ; Retrospective Studies

Anemia, Aplastic ; diagnosis ; pathology ; Humans ; Severity of Illness Index

Aplastic anemia(AA) is mostly considered as an immune-mediated bone marrow failure syndrome, characterized by pancytopenia and bone marrow hypoplasia. The pathogenesis of AA is complicated, until now it is not fully understood. Further study on the pathological mechanism will be helpful for the diagnosis and treatment of AA. CD8(+) T cells and their secreted cytokines play important roles in the abnormal immunity during the process of AA. Thus, this review focuses on the role of CD8(+) T cells and their secreted cytokines in the pathogenesis of AA.
Anemia, Aplastic ; immunology ; metabolism ; pathology ; CD8-Positive T-Lymphocytes ; immunology ; metabolism ; secretion ; Cytokines ; metabolism ; Humans ; Immunity, Cellular

This study was aimed to investigate the changes of CD34(+) and CD71(+)CD45(-) cell levels in MDS and AA patients. A total of 25 cases MDS and 43 cases of AA (18 cases SAA and 25 cases of NSAA) from January 2010 to October 2013 in the Department of Hematology, affiliated hospital of Hebei United University were enrolled in this study. The complete blood count, bone marrow smears, bone marrow biopsy, karyotype analysis and bone marrow blood cell immune genotyping (mainly the proportion of CD34(+) cells, CD71(+)CD45(-) cells in nucleated cells) were carried out for all patients; the changes of CD34(+) and CD71(+)CD45(-) cell levels in patients with MDS and AA (SAA NSAA) were compared; the differences of white blood cell count, platelet count and hemoglobin concentration in patients with count of CD71(+)CD45(-) ≥ 15% or <15% were analyzed. The results showed that the count of CD34(+) in MDS group was higher than that in AA (NSAA and SAA) group (P < 0.05). The count of CD71(+)CD45(-) cells in MDS group was higher than that in SAA (P < 0.05), there was no significant difference between NSAA group and MDS group. In MDS group with CD71(+)CD45(-) ≥ 15%, the platelet count was significantly higher than that in NSAA group (P < 0.05); and there was no statistical difference for leukocyte, platelet count and hemoglobin level between MDS and NSAA group with CD71(+)CD45(-) <15% (P > 0.05). It is concluded that the count of CD34(+) cells in MDS patients is significantly higher than that in AA and SAA patients. The count of CD71(+)CD45(-) cells in MDS group is significantly higher than that of SAA group. The platelet count in MDS patients with CD71(+)CD45(-) cells ≥ 15% is significantly higher than that of the NSAA group.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia, Aplastic ; pathology ; Antigens, CD ; immunology ; Antigens, CD34 ; immunology ; Blood Cell Count ; Bone Marrow ; Bone Marrow Cells ; cytology ; immunology ; Female ; Flow Cytometry ; Humans ; Leukocyte Common Antigens ; immunology ; Male ; Middle Aged ; Myelodysplastic Syndromes ; pathology ; Receptors, Transferrin ; immunology ; Young Adult

This study was aimed to explore the regulation of arsenic trioxide (As₂O₃) on imbalance between adipogenic and osteogenic differentiation of BM-MSC from patients with aplastic anemia(AA). The BM-MSC from AA patients were separated and purified, placed into the adipogenic and osteogenic differentiation culture system, then added the As₂O₃, CsA, As₂O₃combined with CsA were added to corresponding differentiation culture system, the concentration of As₂O₃and CsA were set at 0.001 µmol/ml and 2.5 mmol/ml respectively, the cells were divided into As₂O₃group, the CsA group, combined group and control group (no drug). The cell morphological observation, oil red 'O' staining, Von-Kossa staining, and RT-PCR were used to detect corresponding differentiation marks. The results indicated that in respect to adipogenic differentiation, cellular morphology observing and oil red 'O' staining showed that the rate of adipocyte differentiation in As₂O₃group was (18.3 ± 1.9)%, which was lower than the (91.8 ± 2.7)% in the CsA group and (92.1 ± 1.2)% in control group (P < 0.05), there was no significant difference in comparison with (8.3 ± 1.9)% in the combined group (P > 0.05), but the rate of differentiation in CsA group was higher than that in combined group (P < 0.05), and there was no significant difference in comparison wtih control group. RT-PCR showed that the LPL-mRNA expression level in As₂O₃group were significantly lower than that in the CsA group and the control group (P < 0.05), no difference was observed while compared with the combined group (P > 0.05), but the LPL-mRNA expression level in CsA group was significantly higher than that in the combined group (P < 0.05). In terms of osteogenetic differentiation, the calcium deposition in As₂O₃group and combined group was obviously observed while rarely in the CsA group and the control group when detected by the Von-Kossa staining. OST-mRNA expression level in As₂O₃group were higher than that in CsA group and the control group (P < 0.05), while compared with the combined group, there was no significant difference (P > 0.05), but the OST-mRNA expression level in the CsA group was lower than that in the combined group (P < 0.05). It is concluded that As₂O₃can significantly enhance the ability of BM-MSC from AA patients to differentiate into osteoblast, also can inhibit the adipogenic differentiation, in contrast, the CsA can not promote the osteoblast differentiation of BM-MSC from AA patients.
Adipocytes ; cytology ; drug effects ; Anemia, Aplastic ; pathology ; Arsenicals ; pharmacology ; Bone Marrow ; drug effects ; Cell Differentiation ; drug effects ; Cells, Cultured ; Humans ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Osteoblasts ; Osteogenesis ; drug effects ; Oxides ; pharmacology