Hemoglobin Agenogi in Argentina: Case Report

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4776-4776
Author(s):  
Ana Paula Martin ◽  
Patricia Martha Gargallo ◽  
Irma Margarita Bragos ◽  
Alejandro Abbate ◽  
Mara Jorgelina Ojeda ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Transferrin Saturation ◽  
Serum Vitamin ◽  
Oxygen Affinity ◽  
Peripheral Blood Smear ◽  
Microcytic Anemia ◽  
Hypochromic Microcytic Anemia ◽  
Slow Moving ◽  
Complete Cell ◽  
Unstable Hemoglobin

Abstract Abstract 4776 Hb Agenogi [b90(F6)Glu–>Lys], a beta chain variant was detected in a 44-years-old female patient of italian ancestry. She showed a hypochromic microcytic anemia and was treated as ferropenic anemia since she was 27 years old. The complete cell blood count revealed the following results: RBC: 4.01× 1012/L, PCV:30.9%, Hb:10.4 g/dl, MCV: 77fl, RDW 13.5%, MCH: 25.9 pg, MCHC:33.7%; reticulocytes: 0.6% and the peripheral blood smear showed no basophilic stippling. Serum vitamin B12, folate, iron, transferrin, transferrin saturation and ferritin were normal. The electrophoresis performed on agarose (alkaline pH) revealed a band of 44.5% with a mobility between Hb C and S. The unstable hemoglobin test was positive and the P50 was 31.3 mmHg (NR: 24 –28 mm Hg). This slow-moving hemoglobin, mild unstable and with decreased oxygen affinity was further characterized by sequencing of the amplified DNA, showing the substitution of glutamic acid (GAG) to lysine (AAG) at position 90 of the β globin chain This mutation has been described in only nine families, this is the second affected case in Argentina. Disclosures: No relevant conflicts of interest to declare.

Two New Human DMT1 Mutations in a Compound Heterozygous Patient with Microcytic Anemia and Low Iron Stores.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3540-3540
Author(s):  
Carole Beaumont ◽  
Jean Delaunay ◽  
Gilles Hetet ◽  
Mariane de Montalembert ◽  
Bernard Grandchamp ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Transferrin Receptor ◽  
Serum Iron ◽  
Transmembrane Domain ◽  
Iron Absorption ◽  
Transferrin Saturation ◽  
Microcytic Anemia ◽  
The Other ◽  
Erythroid Cells ◽  
Hypochromic Microcytic Anemia

Abstract DMT1 is a divalent metal transporter with 12 transmembrane domains. It is expressed at the apical membrane of duodenal enterocytes, where it mediates pH-dependent uptake of Fe2+. In erythroid cells, it is found in the endosomal membrane where it transfers iron internalized through the transferrin-transferrin receptor pathway from the endosome to the cytosol. The same homozygous G>A substitution resulting in the G185A replacement is responsible for a severe hypochromic microcytic anemia in both the mk mouse and in the Belgrade rat. In humans, a homozygous G>C mutation has been described in a Czech patient, affecting the last nucleotide of exon 12. This mutation leads to the G399A replacement, without affecting the transport function of the protein. However, this mutation also induces a preferential in-frame skipping of exon 12, albeit not in all tissues. Accordingly, the patient has impaired iron acquisition in erythrocytes while duodenal iron absorption is increased leading to progressive iron overload. Here, we report a female patient born in 1996, with low birth weight and hypochromic microcytic anemia (Hb = 7.5 g/dl; MCV = 53 fL). She was transfused at day 0 and put on oral iron treatment. She was then lost to follow-up for five years. At the age of five, more extensive explorations showed a persistent microcytic anemia. The bone marrow displayed normal cellularity, 30% of nucleated cells were erythroid precursors with a moderate maturation defect, acidophilic forms being under-represented as compared to more immature forms. Soluble transferrin receptors were increased (8.3 mg/L; N = 0.83–1.76). Following oral iron therapy, serum ferritin levels remained low (15–25 μg/L; N = 14–197) despite an increase in transferrin saturation from 68 to 95 %. This high transferrin saturation resulted from the combination of reduced transferrin levels (1.64 g/L, N = 2.2–4.0) and increased serum iron levels (35 μmol/L; N = 11–24). On the other hand, hemoglobin raised from 7 to 9 g/dL only through increased number of RBC (5 to 5.7 T/L), since MCV and MCHC remained unchanged. We sequenced the entire transferrin receptor cDNA in this patient and found no mutation. We then sequenced the exons and the intron-exon boundaries of the DMT1 gene and found two heterozygous mutations. One mutation was a deletion of a GTG codon in exon 5, leading to the V114 in-frame deletion, in transmembrane domain 2. The other mutation is a G>T substitution in exon 8 leading to the G212V replacement in transmembrane domain 5. Both parents were asymptomatic, the father being heterozygous for the delV114 mutation and the mother heterozygous for the G212V mutation. This is the second patient described with a neonatal hypochromic microcytic anemia due to DMT1 mutations. Our data suggest that the two combined DMT1 mutations are responsible for the defect in iron utilization by erythroid cells, resulting in persistant microcytosis and impaired red cell maturation. The effect of the mutations on intestinal iron absorption is more difficult to evaluate since iron therapy allowed serum iron and transferrin saturation to increase but serum ferritin remained low and hemoglobin did not reach normal values.

A NOVEL Mutation of the Erythroid-Specific Aminolevulinate Synthase 2 Gene IN A Patient with Pyridoxine Responsive Sideroblastic Anemia and Deferasirox Responsive Hemochromatosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5105-5105
Author(s):  
Umran Caliskan ◽  
Huseyin Tokgoz ◽  
Hasan Yuksekkaya
Keyword(s):  
Novel Mutation ◽  
Hereditary Hemochromatosis ◽  
Gene Mutations ◽  
Chelating Agent ◽  
Peripheral Blood Smear ◽  
Microcytic Anemia ◽  
Hfe Gene ◽  
Sideroblastic Anemia ◽  
Aminolevulinate Synthase ◽  
Hypochromic Microcytic Anemia

Abstract Abstract 5105 A-14 years-old man, admitted to our clinic with weakness and paleness since one month. He has hepatosplenomegaly. Blood tests and peripheral blood smear showed anemia that severe hypochromic, microcytic anemia. There is ringed sideroblasts without dysplastic hematopoiesis in bone marrow cytology. Liver tests were normal. A liver biopsy showed heavy parenchymal iron deposition and grade-III fibrosis. Screening for HFE gene mutations was negative. MR imaging demonstrated that severe iron accumulation in liver and heart. ALAS2 gene screening showed that novel mutation in exon 7 (Gly390Gly, c.1170, C□T). Eventually, was diagnosed as sideroblastic anemia and hemochromatosis. He was treated successfully with pyridoxine and chelating agent (deferasirox, IGL-670). The findings suggest that the Gly390Gly in ALAS2 mutation causes sideroblastic anemia and hemochromatosis, without hereditary hemochromatosis gene mutations. This mutation cause sideroblastic anemia is clinically pyridoxine-responsive. Deferasirox is effective agent for reduce hepatic iron loading in this condition. Disclosures Off Label Use: deferasiroks was used for hemochromatosis secondary to congenital syderoblastic anemia.

FLVCR1a But Not FLVCR1b Is Required For Effective Erythropoiesis In Adult Mice

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 308-308
Author(s):  
Raymond T Doty ◽  
Marilyn Sanchez-Bonilla ◽  
Siobán B. Keel ◽  
Janis L. Abkowitz
Keyword(s):  
Conflicts Of Interest ◽  
Macrocytic Anemia ◽  
Microcytic Anemia ◽  
Model Systems ◽  
Over Expression ◽  
Post Transplant ◽  
Hypochromic Microcytic Anemia ◽  
Adult Mice ◽  
And Control

Abstract There are two characterized isoforms of FLVCR. The long form, FLVCR1a, is a broadly expressed cell surface heme exporter (Cell 118: 757, 2004) which exports heme from the cytoplasm to an extracellular carrier protein (JBC 285: 28874, 2010). The short isoform, FLVCR1b, is transcribed off an internal promoter and localizes to the mitochondria where it exports heme out of mitochondria into the cytoplasm (JCI 112: 4569, 2012). Adult mice with an induced deletion of both isoforms of FLVCR develop severe macrocytic anemia (Science 319: 825, 2008), indicating that FLVCR is essential for erythropoiesis. Mice constitutively lacking both isoforms of FLVCR die midgestation with craniofacial and digit abnormalities and lack definitive erythropoiesis while mice lacking only FLVCR1a die midgestation with craniofacial and digit abnormalities yet appear to have intact erythropoiesis (Science 319: 825, 2008, JCI 112: 4569, 2012). These results suggest that FLVCR1b, and not FLVCR1a, is required for erythropoiesis. To definitively test whether FLVCR1a or FLVCR1b is sufficient for red cell development, we transplanted mice with marrow lacking both isoforms of FLVCR that had been transduced with either FLVCR1a or FLVCR1b along with a GFP marker. Both cohorts of mice had comparable marking frequency in granulocytes (31.1±16.4%, N=15, FLVCR1a vs 32.7±16.9%, N=8, FLVCR1b) at 4 weeks post-transplant. By 7 wks post-transplant, 71.3±19.7% of the RBC in mice that received FLVCR1a were derived from transduced cells, while only 1.0±0.8% of the RBC in mice that received FLVCR1b were derived from transduced cells. Mice that received FLVCR1a are healthy and have normal CBC parameters (WBC 8.34±4.7 k/ml, RBC 7.95±1.2 M/ml, HGB 12.5±1.7 g/dl, MCV 47.9±2.0 fl , PLT 879±387 k/ml) which persist 9 months later, while mice that received FLVCR1b are severely anemic (WBC 1.9±1.3 k/ml, RBC 1.5±0.6 M/ml, HGB 2.0±0.8 g/dl, MCV 36.5±0.8 fl , PLT 1442±1232 k/ml) and die by 8 weeks post-transplant. This demonstrates that only the FLVCR1a isoform is capable of reconstituting erythropoiesis in adult mice lacking both isoforms in hematopoietic cells. One possible way to reconcile these data with the reported role of FLVCR1b, would be if FLVCR1b were needed during fetal, but not adult, erythropoiesis. As mentioned above, adult mice with an induced deletion of FLVCR develop severe macrocytic anemia (HBG 6.5±2.2 g/dl, MCV 67.9±7.3 fL; vs controls 14.6±0.7, 44.7±3.6), in contrast, over expression of FLVCR1a results in mild hypochromic microcytic anemia (HBG 13.2±1.4 g/dl, MCV 41±5.2 fL; vs controls 15.4±0.5, 49.3±1.3). Because hypochromasia and microcytosis only result from heme or hemoglobin deficiency, FLVCR1a must export heme from differentiating erythroblasts in vivo. To confirm this, we sorted developing erythroblasts from FLVCR-deleted and control mice and measured heme content at each stage. Terminally differentiating erythroid precursors (populations I-IV, PNAS 106: 17413, 2009) from FLVCR-deficient mice have significantly more heme than those from control mice (I&II 359.6±99.9 pg/cell, III 702.2±302.2 pg/cell, IV 657.8±292.9 pg/cell, versus controls 131.4±65.2, 153.9±27.1, and 269.1±102.7 respectively, all p<0.05) and have significantly more apoptosis. To definitively demonstrate that heme toxicity causes proerythroblast apoptosis and macrocytic anemia, we are using existing mouse model systems to modulate impact heme synthesis or degradation and test whether they alter the effect of FLVCR deletion on erythropoiesis. The presence of the ferrochelatase mutation, Fechm1Pas/m1Pas, does not rescue FLVCR deficiency, most likely because the accumulation of toxic precursor products which are also substrates of FLVCR (JBC 285: 28874, 2010). We are currently evaluating whether over-expression of HO-1 or restricted expression of the transferrin receptor can mitigate the effect of FLVCR deletion. Disclosures: No relevant conflicts of interest to declare.

HYPOCHROMIC MICROCYTIC ANEMIA OF INFANCY: IRON DEPLETION AS A FACTOR

PEDIATRICS ◽  
1956 ◽  
Vol 18 (6) ◽  
pp. 959-978
Author(s):  
Hugh W. Josephs
Keyword(s):  
Iron Deficiency ◽  
Severe Infection ◽  
Microcytic Anemia ◽  
Severe Anemia ◽  
Iron Depletion ◽  
Hypochromic Microcytic Anemia ◽  
Premature Babies ◽  
Number Of Factors ◽  
The Difference ◽  
Insight Into

In this work the author has attempted to gain insight into the significance of iron depletion by the use of 4 simple calculations, justification for which is found in recent articles. These are: (a) iron with which the infant is born; (b) iron retained from the food; (c) iron being used by the tissues and therefore unavailable for hemoglobin, and (d) iron combined with the total mass of hemoglobin. With these 4 figures it is possible to estimate the iron still potentially available for use (the "reserves" or "stones"). When the difference between a + b and c + d has reached about zero, depletion is considered to exist. The following characteristics of depletion may be emphasized: Depletion is the result of gain in weight and maximum possible usage of iron. It is therefore a normal result of growth and need not be associated with anemia. As soon as depletion has occurred, the organism is thereafter dependent on current absorption of iron. This is ordinarily sufficient, even with a diet of milk alone, to maintain an adequate concentration of hemoglobin after about 8 to 10 months of age. Severe anemia due to depletion alone is practically confined to premature babies whose relative gain in weight is rapid. Severe anemia in other than premature babies is the result of a number of factors by which iron becomes unavailable or is actually diverted from hemoglobin to storage. Response to iron medication is considerably better in infants with depletion than in those in whom some factor is present that interferes with iron utilization, and which is not connected by the mere giving of iron. The dependence on current absorption, whether the result of depletion or non-availability, introduces a certain precariousness which is apparently characteristic of this time of life. The organism gets along from day to day if nothing happens, but may not be able to meet an emergency, whether this appears as a rapid gain in weight, or a necessity to repair damage done by severe infection. If we consider iron deficiency as the cause of anemia, we can think of deficiency as due to a number of factors of which depletion is only one. The development and characteristics of depletion have been considered in this paper; other factors in iron deficiency will be considered in subsequent papers.

scholarly journals Giant adrenal hemangioma: Unusual cause of huge abdominal mass

2015 ◽  
Vol 9 (11-12) ◽  
pp. 834 ◽  
Author(s):  
Mohamed Tarchouli ◽  
Adil Boudhas ◽  
Moulay Brahim Ratbi ◽  
Mohamed Essarghini ◽  
Noureddine Njoumi ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Abdominal Mass ◽  
Abdominal Distension ◽  
Microcytic Anemia ◽  
Hypochromic Microcytic Anemia ◽  
Normal Limits ◽  
Laboratory Examinations ◽  
Right Lobe ◽  
The Right

Adrenal hemangioma is an extremely rare benign and non-functioning neoplasm of the adrenal gland. We report a case of a 71-year-old woman admitted for intermittent abdominal pain and abdominal distension associated with vomiting and chronic constipation for 5 years. Physical examination revealed a large abdominal mass. Both computed tomography scan and magnetic resonance imaging suggested hemangioma in the right lobe of the liver. Laboratory examinations and tumour markers were within normal limits, except for hypochromic microcytic anemia. The mass was removed intact by conventional surgery and histopathology revealed a cavernous hemangioma of the adrenal gland with no signs of malignancy. Surgical resection was curative, with no recurrence at the 2-year follow-up.

scholarly journals Abnormal megakaryocytopoiesis in the Belgrade laboratory rat

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 456-460 ◽  
Author(s):  
Z Rolovic ◽  
N Basara ◽  
N Stojanovic ◽  
N Suvajdzic ◽  
V Pavlovic-Kentera
Keyword(s):  
Iron Transport ◽  
Basic Mechanism ◽  
Microcytic Anemia ◽  
Severe Anemia ◽  
Erythroid Progenitors ◽  
Hypochromic Microcytic Anemia ◽  
Iron Treatment ◽  
Full Correction ◽  
Partial Correction ◽  
Cell Disorder

Abstract The Belgrade laboratory (b/b) rat has a hereditary hypochromic microcytic anemia because of defective transmembrane iron transport into erythroblasts. The present study was prompted by our previous work in which we showed that the b/b rat has hypomegakaryocytic thrombocytopenia associated with increased megakaryocyte size. To define the basic mechanism underlying this abnormality in the b/b rat we have studied both megakaryocytopoiesis and granulopoiesis in anemic b/b rats, chronically transfused b/b rats, iron-treated b/b rats, and controls. We have found decreased concentrations of megakaryocyte and granulocyte progenitors in the marrow of b/b rats. Full correction of the severe anemia by chronic transfusion resulted in normalization of megakaryocyte progenitors, small acetylcholinesterase positive cells, megakaryocyte size, and platelet counts, along with granulocyte progenitors. In contrast, the partial correction of anemia obtained by iron treatment resulted in improvement, but not normalization, of these parameters. These findings indicate that abnormal megakaryocytopoiesis in the b/b rat can be best interpreted as a consequence of hypoxia because of the severe anemia. Because we have recently shown that the number of erythroid progenitors in b/b rats is also low, we propose that abnormal megakaryocytopoiesis in this animal is a reflection of an acquired stem cell disorder induced by the prolonged hypoxia resulting from the severe anemia.

scholarly journals Echocardiografic Abnormalities in Patients with Sickle Cell/β-Thalassemia Do Not Depend on the β-Thalassemia Phenotype

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 987-987
Author(s):  
Bruno Deltreggia Benites ◽  
Ianara Silva Cisneiros ◽  
Stephany Oliveira Bastos ◽  
Ana Paula Beppler Lazaro Lino ◽  
Fernando Ferreira Costa ◽  
...  
Keyword(s):  
Disease Severity ◽  
Sickle Cell ◽  
Cardiac Involvement ◽  
Myocardial Hypertrophy ◽  
Conflicts Of Interest ◽  
Systolic Function ◽  
Transferrin Saturation ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Acute Chest Syndrome

Abstract Introduction: Heart disease represents an important cause of mortality and morbidity in sickle cell disease and beta-thalassemia, however the impairment of cardiac function in compound heterozygotes, namely sickle cell/β-thalassemia (HbS/β-thal) remains less known. Studies with patients of Greek origin demonstrated abnormal diastolic function in both ventricules, with unchanged systolic function, and biventricular dilatation along with pulmonary hypertension (Aessopos, A., et al., Ann Hematol, 88(6), 2009, Moyssakis, I., et al., Postgrad Med J, 81(961), 2005). The aim of this study was to evaluate echocardiographic findings and clinical and laboratory parameters in a cohort of Brazilian HbS/β-thal patients to better understand the cardiac involvement in this particular ethnic background. Methods: A retrospective chart review was performed on thirty-six HbS/β-thal patients followed from 1998 to 2016. Medical records were reviewed for laboratory and clinical data, and hospital admissions were recorded for sickle related complications: acute chest syndrome, retinopathy, avascular bone necrosis, stroke, priapism, leg ulcers and venous thromboembolism. Echocardiographic evaluation was performed in all patients in steady-state disease, with pulsed, continuous, two-dimensional and color Doppler. Results: Among the studied population, 21 (58%) were women and 15 (42%) were men. The median age was 38 (18-70) years; 22 (61%) patients were diagnosed as Sβ0, and 14 (39%) as Sβ+. As expected, when the Sβ-thalassemia phenotype was considered, the two groups of patients differed significantly: hemoglobin levels were lower in Sβ0 patients, who also presented a higher proportion of HbS and HbF and higher transferrin saturation indexes. Sβ0 patients also demonstrated significantly lower body mass index and higher number of platelets highlighting disease severity in this subgroup of patients. Left atrial (LA) and left ventricular (LV) dilation were found in 19.5 and 11% of patients, respectively. These prevalences are considerably lower than observed in patients with SS phenotype: 78 and 35%, respectively (Damy et al, Eur Heart J, 37(14), 2016). Systolic LV disfunction (defined as LV ejection fraction &lt;59%) was present in only one patient of our cohort, though also uncommon in SS patients (8.5% in the study of Damy et al). There were no significant differences in masses and volumes of cardiac chambers comparing Sβ0 with Sβ+ patients, and we found no relationship between these parameters and the occurrence of specific complications of the disease. However, a significant correlation was found regarding parameters of myocardial hypertrophy with serum creatinine, hepatic transaminases and bilirubin levels. Moreover, among the 36 patients studied, 3 of them (1 Sβ+ and 2 Sβ0) presented stroke; these patients were significantly older (median 53 years x 37.5 years, p = 0.048), had higher values of left ventricular posterior wall diastolic thickness [8 (6-14) x 10 (10-11), p= 0.03], greater left ventricular mass [147 (69-537) x 226 (194-260), p= 0.039] and a significantly higher left atrium / aortic ratio (1.26 (0.9-1,48) x 1.545 (1.48-1.61), p= 0.032). No differences were found in pulmonary artery systolic pressure (PASP) between Sβ+ and Sβ0 patients and there was no relationship between PASP and the occurrence of acute or chronic complications. Discussion: In this cohort of Brazilian patients, we observed significant differences in hematological and clinical parameters between Sβ+ and Sβ0 patients, highlighting the difference in disease severity between the two groups. However, the profile of cardiac involvement analyzed by echocardiography was similar in both groups: higher prevalence of diastolic dysfunction with little systolic function impairment, which follows the patterns of the patients of greek origin. Nevertheless, parameters of myocardial hypertrophy were related to multiorgan impairment, and rendered a higher propensity for stroke in older patients. Thus, cardiac involvement in this disease seems to not depend on the thalassemia phenotype. This may also reflect the older age of subjects evaluated, demonstrating that the exposure to the disease features (anemia/hemolysis/inflammation) renders homogeneity in cardiac damage over time, and represents an alert for greater vigilance and control of associated factors, as hypertension and diabetes. Disclosures No relevant conflicts of interest to declare.

scholarly journals Abnormal megakaryocytopoiesis in the Belgrade laboratory rat

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 60-64 ◽  
Author(s):  
Z Rolovic ◽  
T Jovanovic ◽  
Z Stankovic ◽  
N Marinkovic
Keyword(s):  
Genetic Defect ◽  
Cell Lineage ◽  
Microcytic Anemia ◽  
Severe Anemia ◽  
Red Cell ◽  
Present Evidence ◽  
Hypochromic Microcytic Anemia ◽  
Laboratory Rat ◽  
Maturation Rate ◽  
Normal Rat

The Belgrade laboratory rat (b/b rat) has hereditary, hypochromic, microcytic anemia with a variety of red cell abnormalities. Although this anemic syndrome has been recently ascribed to the defective delivery of iron to the developing red cell, the basic hematopoietic defect is still unknown. In this article we present evidence that the b/b rat has an additional hematologic defect. We have found that the megakaryocyte number in the marrow of the b/b rat is decreased to one half that of the normal rat, but the maturation rate of recognizable megakaryocytes is accelerated and the size is increased. The platelet count is moderately reduced. These findings indicate that megakaryocytopoiesis in the anemic b/b rat is abnormal and suggest that the genetic defect may involve the progenitors of the megakaryocyte cell lineage. Alternatively, the megakaryocytic abnormalities may be secondary to the severe anemia.

scholarly journals Role of Roxadustat in Improving Erythropoiesis-Stimulating Agent (ESA)-Resistant Anemia in Patients on Maintenance Hemodialysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-47
Author(s):  
Satoshi Funakoshi
Keyword(s):  
Iron Metabolism ◽  
Conflicts Of Interest ◽  
Hypoxia Inducible Factor ◽  
Transferrin Saturation ◽  
Hemodialysis Patients ◽  
Maintenance Hemodialysis ◽  
Reactive Protein ◽  
Study Results ◽  
Dialysis Vintage ◽  
Patients With Diabetes

Background: Roxadustat, an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, is shown to stimulate erythropoiesis thus improving iron metabolism. Again, while hyperglycemic states are known to be associated with a decreased tissue hypoxia response, to date, roxadustat has not been revaluated for its role in improving anemia in patients with or without diabetes in clinical settings. Methods: A total of 64 hemodialysis patients being treated with epoetin α (9000 units weekly) participated in the study after giving informed consent. They were switched from intravenous epoetin α to oral roxadustat (100 mg 3 times weekly) therapy and were assessed 8 weeks later for improvements in anemia, as well as for changes in parameters for iron metabolism and C-reactive protein (CRP). Results: The study included 39 patients without diabetes (mean age, 71.1 ± 12.1 years; mean dialysis vintage, 7.5 ± 7.4 years; mean GA, 16.2 ± 2.9%) and 27 patients with diabetes (mean age, 70.3 ± 10.3 years; mean dialysis vintage, 5.9 ± 5.5 years; mean GA, 24.9 ± 5.5%). As shown in Table, after 8 weeks the Hb concentration was significantly increased from 10.3 ± 0.8 g/dL at baseline to 10.7 ± 1.3 g/dL in patients without diabetes (P = 0.03) but was not increased in patients with diabetes (from 10.4 ± 0.6 at baseline to 10.5 ± 1.1 g/dL). Again, the serum iron, ferritin concentrations and the transferrin saturation ratio were decreased, irrespective of whether or not they had diabetes, with no change shown in serum CRP level. Conclusion: Switching hemodialysis patients with ESA-resistant anemia from ESA to roxadustat led to improvements in anemia only in those without diabetes, while study results suggested the involvement of mechanisms, other than impaired iron utilization or inflammation, in the impairment of hematopoiesis in those with diabetes. Table Disclosures No relevant conflicts of interest to declare.

scholarly journals Mutation of the gastric hydrogen-potassium ATPase alpha subunit causes iron-deficiency anemia in mice

Blood ◽  
2011 ◽  
Vol 118 (24) ◽  
pp. 6418-6425 ◽  
Author(s):  
Lara Krieg ◽  
Oren Milstein ◽  
Philippe Krebs ◽  
Yu Xia ◽  
Bruce Beutler ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Absorption ◽  
Osmotic Fragility ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Α Subunit ◽  
Hypochromic Microcytic Anemia ◽  
Gastric Proton Pump ◽  
Potassium Atpase

Abstract Iron is an essential component of heme and hemoglobin, and therefore restriction of iron availability directly limits erythropoiesis. In the present study, we report a defect in iron absorption that results in iron-deficiency anemia, as revealed by an N-ethyl-N-nitrosourea–induced mouse phenotype called sublytic. Homozygous sublytic mice develop hypochromic microcytic anemia with reduced osmotic fragility of RBCs. The sublytic phenotype stems from impaired gastrointestinal iron absorption caused by a point mutation of the gastric hydrogen-potassium ATPase α subunit encoded by Atp4a, which results in achlorhydria. The anemia of sublytic homozygotes can be corrected by feeding with a high-iron diet or by parenteral injection of iron dextran; rescue can also be achieved by providing acidified drinking water to sublytic homozygotes. These findings establish the necessity of the gastric proton pump for iron absorption and effective erythropoiesis.

Sign in / Sign up

Export Citation Format

Share Document