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Megaloblastic Anemia (megaloblastic + anemia)
Selected AbstractsDNA ploidy and cell cycle analyses in the bone marrow cells of patients with megaloblastic anemia using laser scanning cytometry,CYTOMETRY, Issue 2 2008Takayuki Tsujioka Abstract Background: Megaloblastic anemias are characterized by several hematopoietic cells with dysplastic nuclear morphology. The analyses of DNA ploidy and cell cycle of these cells are important to understand the property of such diseases. Methods: As laser scanning cytometry (LSC) is a useful tool to evaluate the morphology of the cells fixed on the slide glass together with the quantitative analysis of the fluorescence information of each cell by rapid scanning of the specimens, the authors examined the DNA ploidy and cell cycle of six cases with megaloblastic anemia using LSC. Results: Giant neutrophilic series such as giant metamyelocytes and giant band cells were found to have extraordinarily higher DNA ploidy, while hypersegmented neutrophils represented the normal diploid pattern like normal neutrophils. As to megaloblasts, cell cycle analysis showed that the proportion of the cells in S phase was increased as compared with the case of normal erythroblasts. Conclusions: The present study clearly demonstrates the abnormal aspects of the hematopoietic cells with megaloblastic anemia from the viewpoint of the DNA ploidy and cell cycle analyzed by the use of LSC. © 2007 Clinical Cytometry Society. [source] Severe vitamin B12 deficiency resulting in pancytopenia, splenomegaly and leukoerythroblastosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2008Thorvardur R. Halfdanarson Abstract Deficiency of vitamin B12 is a well known cause of megaloblastic anemia and pancytopenia. Splenomegaly and leukoerythroblastosis are much less well known manifestations of B12 deficiency. We report a B12 deficient female with severe pancytopenia including normocytic anemia who also had enlarged spleen and circulating nucleated red blood cells as well as circulating immature myeloid cells. Although these findings are reported in the earlier literature, more modern reviews of the subject often fail to mention this association. We review the literature on these unusual manifestations of B12 deficiency and remind clinicians that splenomegaly and erythroblastosis can serve as diagnostic clues in cases of severe megaloblastic anemia secondary to B12 deficiency. [source] Disruption of transport activity in a D93H mutant thiamine transporter 1, from a Rogers Syndrome familyFEBS JOURNAL, Issue 22 2003Dana Baron Rogers syndrome is an autosomal recessive disorder resulting in megaloblastic anemia, diabetes mellitus, and sensorineural deafness. The gene associated with this disease encodes for thiamine transporter 1 (THTR1), a member of the SLC19 solute carrier family including THTR2 and the reduced folate carrier (RFC). Using transient transfections into NIH3T3 cells of a D93H mutant THTR1derived from a Rogers syndrome family, we determined the expression, post-translational modification, plasma membrane targeting and thiamine transport activity. We also explored the impact on methotrexate (MTX) transport activity of a homologous missense D88H mutation in the human RFC, a close homologue of THTR1. Western blot analysis revealed that the D93H mutant THTR1 was normally expressed and underwent a complete N -glycosylation. However, while this mutant THTR1 was targeted to the plasma membrane, it was completely devoid of thiamine transport activity. Consistently, introduction into MTX transport null cells of a homologous D88H mutation in the hRFC did not result in restoration of MTX transport activity, thereby suggesting that D88 is an essential residue for MTX transport activity. These results suggest that the D93H mutation does not interfere with transporter expression, glycosylation and plasma membrane targeting. However, the substitution of this negatively charged amino acid (Asp93) by a positively charged residue (His) in an extremely conserved region (the border of transmembrane domain 2/intracellular loop 2) in the SLC19 family, presumably inflicts deleterious structural alterations that abolish thiamine binding and/or translocation. Hence, this functional characterization of the D93H mutation provides a molecular basis for Rogers syndrome. [source] A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency,HUMAN MUTATION, Issue 1 2004Marilyn M. Gordon Abstract Congenital intrinsic factor (IF) deficiency is a disorder characterized by megaloblastic anemia due to the absence of gastric IF (GIF, GenBank NM_005142) and GIF antibodies, with probable autosomal recessive inheritance. Most of the reported patients are isolated cases without genetic studies of the parents or siblings. Complete exonic sequences were determined from the PCR products generated from genomic DNA of five affected individuals. All probands had the identical variant (g.68A>G) in the second position of the fifth codon in the coding sequence of the gene that introduces a restriction enzyme site for Msp I and predicts a change in the mature protein from glutamine5 (CAG) to arginine5 (CGG). Three subjects were homozygous for this base exchange and two subjects were heterozygous, one of which was apparently a compound heterozygote at positions 1 and 2 of the fifth codon ([g.67C>G] + [g.68A>G]). The other patient, heterozygous for position 2, had one heterozygous unaffected parent. Most parents were heterozygous for this base exchange, confirming the pattern of autosomal recessive inheritance for congenital IF deficiency. cDNA encoding GIF was mutated at base pair g.68 (A>G) and expressed in COS-7 cells. The apparent size, secretion rate, and sensitivity to pepsin hydrolysis of the expressed IF were similar to native IF. The allelic frequency of g.68A>G was 0.067 and 0.038 in two control populations. This sequence aberration is not the cause of the phenotype, but is associated with the genotype of congenital IF deficiency and could serve as a marker for inheritance of this disorder. Hum Mutat 23:85,91, 2004. © 2003 Wiley-Liss, Inc. [source] Evaluation of eosin-5-maleimide flow cytometric test in diagnosis of hereditary spherocytosisINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1p2 2010R. KAR Summary A flow cytometry-based test using eosin-5-maleimide (EMA) dye was used for diagnosis of hereditary spherocytosis (HS). The mean fluorescence intensiy (MFI) of EMA tagged erythrocytes is lower in HS than that in other hemolytic and nonhemolytic anemias. We enrolled 114 subjects comprising 20 confirmed HS, 20 suspected HS/hemolytic anemia (HA), 20 normal controls, 20 other hemolytic anemias [13 autoimmune hemolytic anemia, three congenital dyserythropoietic anemia (CDA), one pyruvate kinase deficiency, two microangiopathic hemolytic anemia], 18 microcytic anemia and 16 macrocytic anemia cases. All samples were subjected to flow cytometry as per standard protocol. The mean MFI of normal control subjects was 11 861.5 (SD 883.5) and of confirmed HS was 7949.3 (SD 1304.1). Using this test, of 20 patients suspected to be HS/HA but with no confirmatory diagnosis, eight patients were diagnosed as HS. Using logistic regression analysis, the optimum cut-off MFI value between HS and normal controls was 10126. The area under the ROC curve was 0.99. The statistical significance of MFI values was obtained by t -test or Wilcoxon rank sum test as applicable. Compared with normal controls, the MFI values in HS were lower and in megaloblastic anemia were higher which was statistically highly significant (P < 0.01), and the MFI values in CDA were lower which was statistically significant (P < 0.05). False-positive values were obtained in three cases of AIHA and two cases of CDA. The sensitivity and specificity was 96.4% and 94.2% respectively. The EMA-based flow cytometry test is a highly sensitive and specific method for the diagnosis of HS. [source] Utility of reticulocyte maturation parameters in the differential diagnosis of macrocytic anemiasINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2003A. Torres Gomez Summary The aim of this study was to test the clinical utility of reticulocyte maturation parameters in the differential diagnosis of macrocytic anemias. Using an automated reticulocyte counter, we analyzed immature reticulocyte fraction (IRF), mean reticulocyte volume (MRV) and mean fluorescence index (MFI) in peripheral blood samples from healthy donors (n = 30), patients diagnosed with myelodysplastic syndromes (MDS, n = 35), with megaloblastic anemia (MA, n = 10) and with non-megaloblastic macrocytic anemias (NMMA, n = 30). Macrocytic anemias due to ineffective erythropoiesis (MA and MDS) showed reticulocytes skewed to a more immature fraction. Therefore, they have a larger volume and a greater RNA content than healthy controls. Interestingly, reticulocytes in both low and high risk MDS are significantly larger (127.3 vs. 118.3 fl, P < 0.01) and have a greater RNA content (MFI 20.5 vs. 12.9, P < 0.01 and IRF 22.5 vs. 9.1%, P < 0.01) than NMMA patients. We conclude that measurement of reticulocyte maturation parameters may be a very useful tool in the differential diagnosis of macrocytic anemia. The presence of extremely high values of IRF (>16%), MFI (>18) and MRV (>129 fl), makes the diagnosis of NMMA very unlikely. An underlying MDS should, therefore, be sought. [source] Schistocytes in megaloblastic anemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2010Barbara J. Bain No abstract is available for this article. [source] Prevalence and etiology of acquired anemia in Medieval York, EnglandAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2005Amy Sullivan Abstract This paper presents three distinct models for the development of acquired anemia: iron-deficiency anemia produced by the inadequate intake and/or absorption of iron, the anemia of chronic disease (ACD) caused by the body's natural iron-withholding defense against microbial invaders, and megaloblastic anemia caused by insufficient intake and/or absorption of vitamin B12 or folic acid. These etiological models are used to interpret the distribution and etiology of anemia among adult individuals interred at the Medieval Gilbertine Priory of St. Andrew, Fishergate, York (n = 147). This bioarchaeological analysis uncovered not only a strong relationship between decreasing status and increasing prevalence of anemia for both men and women, but also identified clear sex-based differences at this site. Within the high-status group, blood and iron loss as a result of rampant parasitism likely produced an environment ripe for the development of iron-deficiency anemia, while the parasitic consumption of vitamin B12 may have caused occasional cases of megaloblastic anemia. As status decreases, the interpretation of anemia becomes more complex, with megaloblastic anemia and ACD emerging as viable, potentially heavy contributors to the anemia experiences of low-status people at St. Andrew's. Apart from status effects, women (especially young women) are disproportionately affected by anemia when compared to men within their own status group and, on average, are also more likely to have experienced anemia than their male peers from other status groups. This suggests that high iron-demand reproductive functions helped to make iron-deficiency anemia a chronic condition in many women's lives irrespective of their status affiliation. Am J Phys Anthropol, 2005. © 2005 Wiley-Liss, Inc. [source] The causes of porotic hyperostosis and cribra orbitalia: A reappraisal of the iron-deficiency-anemia hypothesisAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2009Phillip L. Walker Abstract Porosities in the outer table of the cranial vault (porotic hyperostosis) and orbital roof (cribra orbitalia) are among the most frequent pathological lesions seen in ancient human skeletal collections. Since the 1950s, chronic iron-deficiency anemia has been widely accepted as the probable cause of both conditions. Based on this proposed etiology, bioarchaeologists use the prevalence of these conditions to infer living conditions conducive to dietary iron deficiency, iron malabsorption, and iron loss from both diarrheal disease and intestinal parasites in earlier human populations. This iron-deficiency-anemia hypothesis is inconsistent with recent hematological research that shows iron deficiency per se cannot sustain the massive red blood cell production that causes the marrow expansion responsible for these lesions. Several lines of evidence suggest that the accelerated loss and compensatory over-production of red blood cells seen in hemolytic and megaloblastic anemias is the most likely proximate cause of porotic hyperostosis. Although cranial vault and orbital roof porosities are sometimes conflated under the term porotic hyperostosis, paleopathological and clinical evidence suggests they often have different etiologies. Reconsidering the etiology of these skeletal conditions has important implications for current interpretations of malnutrition and infectious disease in earlier human populations. Am J Phys Anthropol 2009. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||