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Immunologic Research Feb 2017Pernicious anemia is the hematologic manifestation of chronic atrophic gastritis affecting the corpus of the stomach that denudes the gastric mucosa of gastric parietal... (Review)
Review
Pernicious anemia is the hematologic manifestation of chronic atrophic gastritis affecting the corpus of the stomach that denudes the gastric mucosa of gastric parietal cells. Asymptomatic autoimmune gastritis, a chronic inflammatory disease of the gastric mucosa, precedes the onset of corpus atrophy by 10-20 years. The gastritis arises from activation of pathologic Th1 CD4 T cells to gastric H/K ATPase that is normally resident on gastric mucosal secretory membranes. The onset of autoimmune gastritis is marked by circulating parietal cell antibody to gastric H/K ATPase. Gastric parietal cells produce two essential biologics: intrinsic factor and HCl acid. Pernicious anemia is a consequence of intrinsic factor loss and neutralizing intrinsic factor antibody that impairs cobalamin absorption. Acid loss leads to iron deficiency anemia that precedes cobalamin-deficient pernicious anemia by 20 years. Laboratory diagnosis rests on parietal cell antibody with or without intrinsic factor antibody, cobalamin-deficient megaloblastic anemia and elevated serum gastrin from loss of acid secretion. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus.
Topics: Anemia, Pernicious; Animals; Autoimmune Diseases; Gastritis, Atrophic; Humans
PubMed: 27538411
DOI: 10.1007/s12026-016-8841-7 -
Genetics in Medicine : Official Journal... Feb 2019Lesch-Nyhan disease is an inherited metabolic disorder characterized by overproduction of uric acid and neurobehavioral abnormalities. The purpose of this study was to...
PURPOSE
Lesch-Nyhan disease is an inherited metabolic disorder characterized by overproduction of uric acid and neurobehavioral abnormalities. The purpose of this study was to describe macrocytic erythrocytes as another common aspect of the phenotype.
METHODS
The results of 257 complete blood counts from 65 patients over a 23-year period were collected from 2 reference centers where many patients are seen regularly.
RESULTS
Macrocytic erythrocytes occurred in 81-92% of subjects with Lesch-Nyhan disease or its neurological variants. After excluding cases with iron deficiency because it might pseudonormalize erythrocyte volumes, macrocytosis occurred in 97% of subjects. Macrocytic erythrocytes were sometimes accompanied by mild anemia, and rarely by severe anemia.
CONCLUSION
These results establish macrocytic erythrocytes as a very common aspect of the clinical phenotype of Lesch-Nyhan disease and its neurological variants. Macrocytosis is so characteristic that its absence should prompt suspicion of a secondary process, such as iron deficiency. Because macrocytosis is uncommon in unaffected children, it can also be used as a clue for early diagnosis in children with neurodevelopmental delay. Better recognition of this characteristic feature of the disorder will also help to prevent unnecessary diagnostic testing and unnecessary attempts to treat it with folate or B12 supplements.
Topics: Adolescent; Adult; Anemia, Macrocytic; Child; Child, Preschool; Humans; Infant; Lesch-Nyhan Syndrome; Longitudinal Studies; Male; Phenotype; Young Adult
PubMed: 29875418
DOI: 10.1038/s41436-018-0053-1 -
The National Medical Journal of India 2023We report a 26-year-old girl who was diagnosed with diabetes mellitus in her childhood and was treated with insulin. With a history of visual disturbances during her...
We report a 26-year-old girl who was diagnosed with diabetes mellitus in her childhood and was treated with insulin. With a history of visual disturbances during her childhood and anaemia, which was partially evaluated; the possibility of syndromic diabetes was considered. Genetic analysis was done and revealed a mutation in the SLC19A2 gene, confirming the diagnosis of thiamine-responsive megaloblastic anaemia. She was supplemented with thiamine, which dramatically improved her haemoglobin levels and glucose control. However, her vision could not be salvaged as the rod-cone dystrophy is a permanent damage.
Topics: Humans; Female; Anemia, Megaloblastic; Adult; Thiamine; Thiamine Deficiency; Membrane Transport Proteins; Mutation; Vitamin B Complex; Diabetes Mellitus; Hearing Loss, Sensorineural
PubMed: 38759983
DOI: 10.25259/NMJI_20_21 -
Seminars in Hematology Oct 2015Myelodysplastic syndromes (MDS) are a constellation of different diseases sharing anemia in the great majority of cases, and this cytopenia defines these pathologies and... (Review)
Review
Myelodysplastic syndromes (MDS) are a constellation of different diseases sharing anemia in the great majority of cases, and this cytopenia defines these pathologies and their most dramatic clinical manifestations. Anemia in MDS is due to ineffective erythropoiesis, with a high degree of apoptosis of marrow erythroid progenitors. These progenitors show distinctive dysplastic features that consent diagnosis, and are recognizable and differentiated, although not easily, from other morphologic alterations present in other types of anemia. Reaching the diagnosis of MDS in a macrocytic anemia and alleviating the symptoms of anemia are therefore an essential objective of the treating physician. In this work, the signs and symptoms of anemia in MDS, as well as its peculiar pathophysiology, are discussed. Erythopoietic stimulating agents (ESAs) are providing the best treatment for anemic MDS patients, but their use is still not approved by health agencies. While still waiting for this waiver, their clinical use is widespread and their effectivness is well known, as well as the dismal prognosis of patients who do not respond to ESAs and require transfusions. MDS with del5q constitute a unique model of anemia whose complex pathophysiology has been clarified at least partially, defining its link to ribosomal alterations likewise what observed in hereditary anemias like Blackfan Diamond anemia. Lenalidomide is the agent that has shown striking and specific erythropoietic activity in del5q MDS, and the basis of this response is starting to be understood. Several new agents are under evaluation for ESA refractory/relapsed MDS patients, targeting different putative mechanisms of ineffective erythropoiesis, and are here reviewed.
Topics: Anemia; Apoptosis; Chromosomes, Human, Pair 15; Humans; Myelodysplastic Syndromes; Prognosis
PubMed: 26404446
DOI: 10.1053/j.seminhematol.2015.06.002 -
[Rinsho Ketsueki] the Japanese Journal... 2018Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by cytopenia and leukemic transformation. Allogeneic hematopoietic stem cell... (Review)
Review
Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by cytopenia and leukemic transformation. Allogeneic hematopoietic stem cell transplantation is the only potential curative therapy for MDS; however, the first treatment option for transfusion-independent patients with low-risk MDS remains limited. Recently, lenalidomide has become available for patients with low-risk MDS and symptomatic anemia with del (5q) (5q-syndrome), darbepoetin (DA) for those with anemia without del (5q), and azacitidine for those with DA-resistant anemia or anemia with thrombocytopenia. DA may be the first treatment option for anemic patients with low-risk MDS because the incidence of 5q-syndrome is rare in Japan in contrast to western countries. It has been reported that primary or secondary failure of Erythropoiesis-stimulating agents (ESA) correlated with a higher risk of acute myeloid leukemia, and none of the leading second-line treatments significantly improved survival. In this review, I have described the treatment strategies in using such drugs and future perspectives for low-risk MDS.
Topics: Anemia, Macrocytic; Azacitidine; Darbepoetin alfa; Humans; Lenalidomide; Myelodysplastic Syndromes
PubMed: 30305508
DOI: 10.11406/rinketsu.59.2050 -
Haematologica May 2023Diamond-Blackfan anemia (DBA) is a ribosomopathy that is characterized by macrocytic anemia, congenital malformations, and early onset during childhood. Genetic studies... (Review)
Review
Diamond-Blackfan anemia (DBA) is a ribosomopathy that is characterized by macrocytic anemia, congenital malformations, and early onset during childhood. Genetic studies have demonstrated that most patients carry mutations in one of the 20 related genes, most of which encode ribosomal proteins (RP). Treatment of DBA includes corticosteroid therapy, chronic red blood cell transfusion, and other forms of immunosuppression. Currently, hematopoietic stem cell transplantation is the only cure for DBA. Interestingly, spontaneous remissions occur in 10-20% of transfusion-dependent DBA patients. However, there is no consistent association between specific mutations and clinical manifestations. In the past decades, researchers have made significant progress in understanding the pathogenesis of DBA, but it remains unclear how the ubiquitous RP haploinsufficiency causes the erythroid-specific defect in hematopoiesis in DBA patients, and why there is a difference in penetrance and spontaneous remission among individuals who carry identical mutations. In this paper, we provide a comprehensive review of the development of DBA animal models and discuss the future research directions for these important experimental systems.
Topics: Animals; Anemia, Diamond-Blackfan; Ribosomal Proteins; Mutation; Models, Animal; Hematopoiesis
PubMed: 36384250
DOI: 10.3324/haematol.2022.282042 -
Cardiovascular & Hematological Agents... Nov 2017Pernicious Anemia (PA), the most common cause of cobalamin deficiency anemia worldwide, is an autoimmune disease of multifactorial etiologies involving complex... (Review)
Review
BACKGROUND
Pernicious Anemia (PA), the most common cause of cobalamin deficiency anemia worldwide, is an autoimmune disease of multifactorial etiologies involving complex environmental and immunological factors. Although it was first reported by Addison in 1849 with subsequent advances in understanding of pathogenesis and molecular biology, diagnosis of PA is still challenging for clinicians because of its complexity and diverse clinical presentations.
CONCLUSION
Herein, we provide an overview of PA, mainly focusing on its scientific and practical aspects in diagnosis. We also discuss the limitations of currently available diagnostic tools for the evaluation of cobalamin deficiency and PA.
Topics: Anemia, Pernicious; Autoantibodies; Gastritis, Atrophic; Humans; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 28164751
DOI: 10.2174/1871525715666170203114632 -
F1000Research 2018Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia characterized by a block in erythropoiesis at the progenitor stage, although the exact stage at... (Review)
Review
Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia characterized by a block in erythropoiesis at the progenitor stage, although the exact stage at which this occurs remains to be fully defined. DBA presents primarily during infancy with macrocytic anemia and reticulocytopenia with 50% of cases associated with a variety of congenital malformations. DBA is most frequently due to a sporadic mutation (55%) in genes encoding several different ribosomal proteins, although there are many cases where there is a family history of the disease with varying phenotypes. The erythroid tropism of the disease is still a matter of debate for a disease related to a defect in global ribosome biogenesis. Assessment of biological features in conjunction with genetic testing has increased the accuracy of the diagnosis of DBA. However, in certain cases, it continues to be difficult to firmly establish a diagnosis. This review will focus on the diagnosis of DBA along with a description of new advances in our understanding of the pathophysiology and treatment recommendations for DBA.
Topics: Abnormalities, Multiple; Anemia, Diamond-Blackfan; Humans
PubMed: 30228860
DOI: 10.12688/f1000research.15542.1 -
Frontiers in Pharmacology 2021Mean corpuscular volume (MCV) is major used as an indicator for the differential diagnosis of anemia. Macrocytic anemia in decompensated cirrhosis is common. However,...
Mean corpuscular volume (MCV) is major used as an indicator for the differential diagnosis of anemia. Macrocytic anemia in decompensated cirrhosis is common. However, the relationship between macrocytic anemia and decompensated hepatitis B virus (HBV) associated cirrhosis has not been fully addressed. In this cross-sectional study, a total of 457 patients diagnosed decompensated HBV associated cirrhosis who met all inclusion criteria from 2011 to 2018 were analyzed. Association between macrocytic anemia and the liver damaged (Model for End Stage Liver Disease (MELD) score) were examined using multiple logistic regression analyses and identified using smooth curve fitting. Compared with normocytic anemia, MCV and MELD are significantly positively correlated in macrocytic anemia ( < 0.001). A non-linear relationship of MCV and MELD association was found though the piecewise linear spline models in patients with decompensated HBV associated cirrhosis. MCV positive correlated with MELD when the MCV was greater than 98.2 fl (regression coefficient = 0.008, 95% CI 0.1, 0.4). Macrocytic anemia may be a reliable predictor for mortality because it is closely related to the degree of liver damage in patients with decompensated HBV associated cirrhosis.
PubMed: 34616304
DOI: 10.3389/fphar.2021.755625 -
Current Opinion in Hematology May 2017Myelodysplastic syndromes (MDS) are heterogeneous diseases of the hematopoietic stem cell in the elderly. Anemia is the main symptom that mostly correlates with... (Review)
Review
PURPOSE OF REVIEW
Myelodysplastic syndromes (MDS) are heterogeneous diseases of the hematopoietic stem cell in the elderly. Anemia is the main symptom that mostly correlates with dysplastic erythropoiesis in the bone marrow. We will review the recent advances in understanding the diverse mechanisms of dyserythropoiesis.
RECENT FINDINGS
Dyserythropoiesis defined as 10% dysplastic erythroid cells in the bone marrow is found in more than 80% of early MDS. Immature erythroblasts accumulate at the expense of mature erythroblasts due to differentiation arrest and apoptosis. In early MDS with dyserythropoiesis, caspase-dependent cleavage of the erythroid transcription factor GATA-1 occurring in basophilic erythroblasts accounts for impairment of final maturation. Depending on initiating genetic alteration, specific mechanisms contribute to erythroid defect. In MDS with 5q deletion, the haploinsufficiency of ribosomal protein gene, RPS14, opposes the transition of immature to mature erythroblasts by inducing a p53-dependent ribosome stress, cell cycle arrest and apoptosis. Recent work identifies the activation of a p53-S100A8/9 innate immune pathway that both intrinsically and extrinsically contributes to defective erythropoiesis. In MDS with ring sideroblasts, a paradigm of dyserythropoiesis, a unique mutation in SF3B1 splicing factor gene induces a multiplicity of alterations at RNA level that deeply modifies the patterns of gene expression.
SUMMARY
Insights in the pathophysiology of MDS with dyserythropoiesis may guide the choice of the appropriate therapy, for instance lenalidomide in MDS with del(5q). A better understanding of the mechanisms of dyserthropoiesis is required to treat anemia in non-del(5q) MDS, especially in case of resistance to first-line therapy by erythropoiesis-stimulating agents.
Topics: Anemia, Macrocytic; Anemia, Sideroblastic; Animals; Bone Marrow; Bone Marrow Cells; Chromosome Deletion; Chromosomes, Human, Pair 5; Erythroid Cells; Erythropoiesis; GATA1 Transcription Factor; Gene Expression Regulation; Humans; Immunity, Innate; Mitochondria; Myelodysplastic Syndromes; RNA Splicing; Signal Transduction
PubMed: 28072603
DOI: 10.1097/MOH.0000000000000325