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CMAJ : Canadian Medical Association... Jul 2016
Topics: Aged; Anemia, Macrocytic; Bone Marrow; Erythropoietin; Fatigue; Humans; Lenalidomide; Myelodysplastic Syndromes; Stem Cell Transplantation; Thalidomide
PubMed: 26728842
DOI: 10.1503/cmaj.151077 -
World Journal of Gastroenterology Nov 2009Pernicious anemia (PA) is a macrocytic anemia that is caused by vitamin B(12) deficiency, as a result of intrinsic factor deficiency. PA is associated with atrophic body... (Review)
Review
Pernicious anemia (PA) is a macrocytic anemia that is caused by vitamin B(12) deficiency, as a result of intrinsic factor deficiency. PA is associated with atrophic body gastritis (ABG), whose diagnosis is based on histological confirmation of gastric body atrophy. Serological markers that suggest oxyntic mucosa damage are increased fasting gastrin and decreased pepsinogen I. Without performing Schilling's test, intrinsic factor deficiency may not be proven, and intrinsic factor and parietal cell antibodies are useful surrogate markers of PA, with 73% sensitivity and 100% specificity. PA is mainly considered a disease of the elderly, but younger patients represent about 15% of patients. PA patients may seek medical advice due to symptoms related to anemia, such as weakness and asthenia. Less commonly, the disease is suspected to be caused by dyspepsia. PA is frequently associated with autoimmune thyroid disease (40%) and other autoimmune disorders, such as diabetes mellitus (10%), as part of the autoimmune polyendocrine syndrome. PA is the end-stage of ABG. Long-standing Helicobacter pylori infection probably plays a role in many patients with PA, in whom the active infectious process has been gradually replaced by an autoimmune disease that terminates in a burned-out infection and the irreversible destruction of the gastric body mucosa. Human leucocyte antigen-DR genotypes suggest a role for genetic susceptibility in PA. PA patients should be managed by cobalamin replacement treatment and monitoring for onset of iron deficiency. Moreover, they should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.
Topics: Anemia, Pernicious; Gastritis, Atrophic; Helicobacter Infections; Humans; Thyroiditis, Autoimmune; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex
PubMed: 19891010
DOI: 10.3748/wjg.15.5121 -
The EMBO Journal Jul 2022Red blood cells are produced by terminal erythroid differentiation, which involves the dramatic morphological transformation of erythroblasts into enucleated...
Red blood cells are produced by terminal erythroid differentiation, which involves the dramatic morphological transformation of erythroblasts into enucleated reticulocytes. Microtubules are important for enucleation, but it is not known if the centrosome, a key microtubule-organizing center, is required as well. Mice lacking the conserved centrosome component, CDK5RAP2, are likely to have defective erythroid differentiation because they develop macrocytic anemia. Here, we show that fetal liver-derived, CDK5RAP2-deficient erythroid progenitors generate fewer and larger reticulocytes, hence recapitulating features of macrocytic anemia. In erythroblasts, but not in embryonic fibroblasts, loss of CDK5RAP2 or pharmacological depletion of centrosomes leads to highly aberrant spindle morphologies. Consistent with such cells exiting mitosis without chromosome segregation, tetraploidy is frequent in late-stage erythroblasts, thereby giving rise to fewer but larger reticulocytes than normal. Our results define a critical role for CDK5RAP2 and centrosomes in spindle formation specifically during blood production. We propose that disruption of centrosome and spindle function could contribute to the emergence of macrocytic anemias, for instance, due to nutritional deficiency or exposure to chemotherapy.
Topics: Anemia, Macrocytic; Animals; Cell Cycle Proteins; Centrosome; Chromosome Segregation; Mice; Microtubules; Mitosis; Spindle Apparatus
PubMed: 35678476
DOI: 10.15252/embj.2021108739 -
British Journal of Haematology Sep 1999
Topics: Aged; Anemia, Macrocytic; Chromosome Deletion; Chromosomes, Human, Pair 5; Female; Humans; Karyotyping; Syndrome
PubMed: 10519982
DOI: 10.1046/j.1365-2141.1999.106004841.x -
The Western Journal of Medicine Apr 1987The laboratory evaluation of anemia begins with a complete blood count and reticulocyte count. The anemia is then categorized as microcytic, macrocytic or normocytic,...
The laboratory evaluation of anemia begins with a complete blood count and reticulocyte count. The anemia is then categorized as microcytic, macrocytic or normocytic, with or without reticulocytosis. Examination of the peripheral smear and a small number of specific tests confirm the diagnosis. The serum iron level, total iron-binding capacity, serum ferritin level and hemoglobin electrophoresis generally separate the microcytic anemias. The erythrocyte size-distribution width may be particularly helpful in distinguishing iron deficiency from thalassemia minor. Significant changes have occurred in the laboratory evaluation of macrocytic anemia, and a new syndrome of nitrous oxide-induced megaloblastosis and neurologic dysfunction has been recognized. A suggested approach to the hemolytic anemias includes using the micro-Coombs' test and ektacytometry. Finally, a number of causes have been identified for normocytic anemia without reticulocytosis, including normocytic megaloblastic anemia and the acquired immunodeficiency syndrome.
Topics: Anemia; Anemia, Macrocytic; Diagnosis, Differential; Humans
PubMed: 3577135
DOI: No ID Found -
Science (New York, N.Y.) Aug 2013Ribosomes are essential in all cell types, yet mutations to ribosomal proteins or assembly factors cause tissue-specific disease.
Ribosomes are essential in all cell types, yet mutations to ribosomal proteins or assembly factors cause tissue-specific disease.
Topics: Anemia, Diamond-Blackfan; Anemia, Macrocytic; Animals; Chromosome Deletion; Chromosomes, Human, Pair 5; Genetic Diseases, Inborn; Humans; Mice; Mutation; Organ Specificity; Ribosomal Proteins; Ribosomes
PubMed: 23970686
DOI: 10.1126/science.1244156 -
Acta Haematologica 1979
Topics: Agglutinins; Anemia, Macrocytic; Autoantibodies; Cold Temperature; Diagnostic Errors; Erythrocyte Count; Hemoglobins; Humans; Male; Middle Aged
PubMed: 105543
DOI: 10.1159/000207628 -
Clinical Medicine & Research Sep 2006
Review
Topics: Anemia, Macrocytic; Anemia, Megaloblastic; Folic Acid Deficiency; Humans; Megaloblasts; Vitamin B 12 Deficiency
PubMed: 16988104
DOI: 10.3121/cmr.4.3.236 -
Science Translational Medicine May 2016Diamond Blackfan anemia (DBA) and myelodysplastic syndrome (MDS) with isolated del(5q) are severe macrocytic anemias; although both are associated with impaired ribosome...
Diamond Blackfan anemia (DBA) and myelodysplastic syndrome (MDS) with isolated del(5q) are severe macrocytic anemias; although both are associated with impaired ribosome assembly, why the anemia occurs is not known. We cultured marrow cells from DBA (n = 3) and del(5q) MDS (n = 6) patients and determined how heme (a toxic chemical) and globin (a protein) are coordinated. We show that globin translation initiates slowly, whereas heme synthesis proceeds normally. This results in insufficient globin protein, excess heme and excess reactive oxygen species in early erythroid precursors, and CFU-E (colony-forming unit-erythroid)/proerythroblast cell death. The cells that can more rapidly and effectively export heme or can slow heme synthesis preferentially survive and appropriately mature. Consistent with these observations, treatment with 10 μM succinylacetone, a specific inhibitor of heme synthesis, improved the erythroid cell output of DBA and del(5q) MDS marrow cultures by 68 to 95% (P = 0.03 to 0.05), whereas the erythroid cell output of concurrent control marrow cultures decreased by 4 to 13%. Our studies demonstrate that erythropoiesis fails when heme exceeds globin. Our data further suggest that therapies that decrease heme synthesis (or facilitate heme export) could improve the red blood cell production of persons with DBA, del(5q) MDS, and perhaps other macrocytic anemias.
Topics: Adult; Anemia; Anemia, Diamond-Blackfan; Anemia, Macrocytic; Erythroid Cells; Erythropoiesis; Female; Flow Cytometry; Globins; Heme; Humans; Myelodysplastic Syndromes; Reactive Oxygen Species
PubMed: 27169803
DOI: 10.1126/scitranslmed.aaf3006 -
Blood Oct 2016
Topics: Aged, 80 and over; Anemia, Macrocytic; Diagnosis, Differential; Humans; Leukemia, Myeloid, Acute; Lymphoma, B-Cell, Marginal Zone; Male; Splenic Neoplasms
PubMed: 28157680
DOI: 10.1182/blood-2016-07-727958