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The Netherlands Journal of Medicine May 2003Aplastic anaemia is featured by bone marrow hypocellularity and peripheral pancytopenia and is a potentially fatal disease. In recent years, insight in it pathogenesis... (Review)
Review
Aplastic anaemia is featured by bone marrow hypocellularity and peripheral pancytopenia and is a potentially fatal disease. In recent years, insight in it pathogenesis has increased. It appears that activated autoreactive T lymphocytes induce apoptosis of haematopoietic stem cells resulting in a hypocellular bone marrow. Nowadays, it can be treated by stem cell transplantation or immunosuppressive therapy. This review focuses on the pathophysiology and treatment of aplastic anaemia.
Topics: Anemia, Aplastic; Humans
PubMed: 12916541
DOI: No ID Found -
American Family Physician Nov 2000Anemia is a common problem that is often discovered on routine laboratory tests. Its prevalence increases with age, reaching 44 percent in men older than 85 years.... (Review)
Review
Anemia is a common problem that is often discovered on routine laboratory tests. Its prevalence increases with age, reaching 44 percent in men older than 85 years. Normocytic anemia is the most frequently encountered type of anemia. Anemia of chronic disease, the most common normocytic anemia, is found in 6 percent of adult patients hospitalized by family physicians. The goals of evaluation and management are to make an accurate and efficient diagnosis, avoid unnecessary testing, correct underlying treatable causes and ameliorate symptoms when necessary. The evaluation begins with a thorough history and a careful physical examination. Basic diagnostic studies include the red blood cell distribution width, corrected reticulocyte index and peripheral blood smear; further testing is guided by the results of these studies. Treatment should be directed at correcting the underlying cause of the anemia. A recent advance in treatment is the use of recombinant human erythropoietin.
Topics: Adult; Anemia, Aplastic; Anemia, Hemolytic; Child; Chronic Disease; Erythrocytes; Female; Humans; Middle Aged; Patient Education as Topic; Teaching Materials
PubMed: 11126852
DOI: No ID Found -
Clinical and Experimental Immunology Jun 2015Immune-mediated destruction of haematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired aplastic anaemia (aAA). Dysregulated... (Review)
Review
Immune-mediated destruction of haematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired aplastic anaemia (aAA). Dysregulated CD8(+) cytotoxic T cells, CD4(+) T cells including T helper type 1 (Th1), Th2, regulatory T cells and Th17 cells, natural killer (NK) cells and NK T cells, along with the abnormal production of cytokines including interferon (IFN)-γ, tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β, induce apoptosis of HSPCs, constituting a consistent and defining feature of severe aAA. Alterations in the polymorphisms of TGF-β, IFN-γ and TNF-α genes, as well as certain human leucocyte antigen (HLA) alleles, may account for the propensity to immune-mediated killing of HSPCs and/or ineffective haematopoiesis. Although the inciting autoantigens remain elusive, autoantibodies are often detected in the serum. In addition, recent studies provide genetic and molecular evidence that intrinsic and/or secondary deficits in HSPCs and bone marrow mesenchymal stem cells may underlie the development of bone marrow failure.
Topics: Anemia, Aplastic; Animals; Cytokines; Disease Susceptibility; Genetic Predisposition to Disease; Hematopoietic Stem Cells; Humans; Immunity, Innate; Immunomodulation; Mesenchymal Stem Cells; T-Lymphocyte Subsets
PubMed: 25683099
DOI: 10.1111/cei.12605 -
Haematologica Oct 2017A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome...
A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70-80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking. We performed a national retrospective study to determine the incidence, treatment, and survival of patients with aplastic anemia diagnosed in Sweden from 2000-2011. Patients were included via the National Patient Registry, and diagnosed according to the Camitta criteria. In total, 257 confirmed cases were identified, with an overall incidence of 2.35 (95% CI: 2.06-2.64) cases per million inhabitants per year. Median age was 60 years (range: 2-92), and median follow up was 76 (0-193) months. Primary treatments included immunosuppressive therapy (63%), allogenic stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy (27%). The 5-year survival was 90.7% in patients aged 0-18 years, 90.5% in patients aged 19-39 years, 70.7% in patients aged 40-59 years, and 38.1% in patients aged ≥60 years. Multivariate analysis showed that age (both 40-59 and ≥60 age groups), very severe aplastic anemia and single-agent cyclosporine/no specific therapy were independent risk factors for inferior survival. In conclusion, younger aplastic anemia patients experience a very good long-term survival, while that of patients ≥60 years in particular remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients, and prospective studies to address this medical need are warranted.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Aplastic; Child; Child, Preschool; Combined Modality Therapy; Female; History, 21st Century; Humans; Incidence; Male; Middle Aged; Patient Outcome Assessment; Population Surveillance; Proportional Hazards Models; Registries; Retrospective Studies; Severity of Illness Index; Survival Analysis; Sweden; Young Adult
PubMed: 28751565
DOI: 10.3324/haematol.2017.169862 -
Cell Death & Disease Apr 2022In acquired immune aplastic anemia (AA), pathogenic cytotoxic Th1 cells are activated and expanded, driving an immune response against the hematopoietic stem and...
In acquired immune aplastic anemia (AA), pathogenic cytotoxic Th1 cells are activated and expanded, driving an immune response against the hematopoietic stem and progenitor cells (HSPCs) that provokes cell depletion and causes bone marrow failure. However, additional HSPC defects may contribute to hematopoietic failure, reflecting on disease outcomes and response to immunosuppression. Here we derived induced pluripotent stem cells (iPSCs) from peripheral blood (PB) erythroblasts obtained from patients diagnosed with immune AA using non-integrating plasmids to model the disease. Erythroblasts were harvested after hematologic response to immunosuppression was achieved. Patients were screened for germline pathogenic variants in bone marrow failure-related genes and no variant was identified. Reprogramming was equally successful for erythroblasts collected from the three immune AA patients and the three healthy subjects. However, the hematopoietic differentiation potential of AA-iPSCs was significantly reduced both quantitatively and qualitatively as compared to healthy-iPSCs, reliably recapitulating disease: differentiation appeared to be more severely affected in cells from the two patients with partial response as compared to the one patient with complete response. Telomere elongation and the telomerase machinery were preserved during reprogramming and differentiation in all AA-iPSCs. Our results indicate that iPSCs are a reliable platform to model immune AA and recapitulate clinical phenotypes. We propose that the immune attack may cause specific epigenetic changes in the HSPCs that limit adequate proliferation and differentiation.
Topics: Anemia, Aplastic; Bone Marrow Failure Disorders; Cell Differentiation; Hematopoietic Stem Cells; Humans; Induced Pluripotent Stem Cells
PubMed: 35484113
DOI: 10.1038/s41419-022-04850-5 -
Journal of Clinical Laboratory Analysis Nov 2012Management of aplastic anemia is etiology driven, whether constitutional or acquired. Age, gender, and severity of disease also play crucial role in the survival of...
BACKGROUND
Management of aplastic anemia is etiology driven, whether constitutional or acquired. Age, gender, and severity of disease also play crucial role in the survival of aplastic anemia. Since, inadequate data are available from India, the present study was conducted with the aim to evaluate the etiology and survival of aplastic anemia.
METHODS
Three hundred patients were enrolled between May 2007 and April 2010. Severity analysis and chromosomal breakage study was performed and patients were followed up to calculate the survival rate.
RESULTS
Only 9.4% of the cases demonstrated the evidence of constitutional disease. Patients with acquired disease showed a significantly higher odd ratio for hepatitis. Overall survival was found to be independent of the gender and inherited etiology. Phenotype resembling to constitutional disease was present in only 22.22% (6/27) of patients. Similar ratio of the constitutional and acquired disease in both the age groups was observed.
CONCLUSION
Irrespective of the age and phenotype, chromosomal breakage study should be mandatory for all patients with aplastic anemia. Hepatitis as a preceding event may be associated with the cause of aplastic anemia. Young age and less severe disease were strongly associated with better survival. Lack of tertiary care facility in the country, time lag between diagnosis and treatment, and unaffordability to abide the treatment cost could be the major contributory factors for poorer survival.
Topics: Adolescent; Adult; Anemia, Aplastic; Child; Child, Preschool; Chromosome Breakage; Communicable Diseases; Female; Humans; Infant; Male; Middle Aged; Odds Ratio; Phenotype; Survival Analysis
PubMed: 23143628
DOI: 10.1002/jcla.21546 -
Blood Oct 2006Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. Almost universally fatal just a few decades ago, aplastic... (Review)
Review
Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. Almost universally fatal just a few decades ago, aplastic anemia can now be cured or ameliorated by stem-cell transplantation or immunosuppressive drug therapy. The pathophysiology is immune mediated in most cases, with activated type 1 cytotoxic T cells implicated. The molecular basis of the aberrant immune response and deficiencies in hematopoietic cells is now being defined genetically; examples are telomere repair gene mutations in the target cells and dysregulated T-cell activation pathways. Immunosuppression with antithymocyte globulins and cyclosporine is effective at restoring blood-cell production in the majority of patients, but relapse and especially evolution of clonal hematologic diseases remain problematic. Allogeneic stem-cell transplant from histocompatible sibling donors is curative in the great majority of young patients with severe aplastic anemia; the major challenges are extending the benefits of transplantation to patients who are older or who lack family donors. Recent results with alternative sources of stem cells and a variety of conditioning regimens to achieve their engraftment have been promising, with survival in small pediatric case series rivaling conventional transplantation results.
Topics: Anemia, Aplastic; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; T-Lymphocytes
PubMed: 16778145
DOI: 10.1182/blood-2006-03-010777 -
Haematologica Jun 2011
Topics: Anemia, Aplastic; Child; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Transplantation, Homologous
PubMed: 21632841
DOI: 10.3324/haematol.2011.044917 -
Experimental Hematology Dec 2018Single-stranded oligonucleotides containing deoxyuridine are aptamers (SOMAmers) that can bind proteins with high specificity and affinity and slow dissociation rates....
Single-stranded oligonucleotides containing deoxyuridine are aptamers (SOMAmers) that can bind proteins with high specificity and affinity and slow dissociation rates. SOMAscan, an aptamer-based proteomic technology, allows measurement of more than 1,300 proteins simultaneously for the identification of new disease biomarkers. The aim of the present study was to identify new serum and plasma protein markers for diagnosis of acquired aplastic anemia (AA) and response to immunosuppressive therapies (IST). SOMAscan was used to screen 1,141 serum proteins in 28 AA patients before and after therapy and 1,317 plasma proteins in seven SAA patients treated with standard IST and a thrombopoietin receptor agonist. From our analysis, 19 serum and 28 plasma proteins were identified as possible candidate diagnostic and prognostic markers. A custom immunobead-based multiplex assay with five selected serum proteins (BMP-10, CCL17, DKK1, HGF, and SELL) was used for validation in a verification set (n = 65) of samples obtained before and after IST and in a blinded validation cohort at baseline (n = 16). After technical validation, four biomarkers were employed to predict diagnosis (accuracy, 88%) and long-term response to IST (accuracy, 79%). In conclusion, SOMAscan is a powerful tool for the identification of new biomarkers. We propose further larger studies to validate new candidate serum and plasma diagnostic and prognostic markers of AA.
Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Aptamers, Nucleotide; Benzoates; Biomarkers; Blood Proteins; Child; Child, Preschool; Female; Humans; Hydrazines; Immunosuppressive Agents; Male; Middle Aged; Molecular Targeted Therapy; Proteomics; Pyrazoles; Receptors, Thrombopoietin; Young Adult
PubMed: 30312735
DOI: 10.1016/j.exphem.2018.09.008 -
Journal of Postgraduate Medicine 2021
Topics: Anemia, Aplastic; Hematopoietic Stem Cell Transplantation; Humans; Stem Cell Transplantation
PubMed: 34845888
DOI: 10.4103/jpgm.JPGM_64_21