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 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 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 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.

Two nonsense mutations in the TMPRSS6 gene in a patient with microcytic anemia and iron deficiency

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 2089-2091 ◽  
Author(s):  
Flavia Guillem ◽  
Sarah Lawson ◽  
Caroline Kannengiesser ◽  
Mark Westerman ◽  
Carole Beaumont ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Microcytic Anemia ◽  
Deficiency Anemia ◽  
Nonsense Mutations ◽  
Hepcidin Expression ◽  
Hypochromic Microcytic Anemia ◽  
Iv Iron ◽  
Membrane Bound ◽  
Inherited Mutations ◽  
Iron Utilization

Abstract Genetic causes of hypochromic microcytic anemia include thalassemias and some rare inherited diseases such as DMT1 deficiency. Here, we show that iron deficiency anemia with poor intestinal absorption and defective iron utilization of IV iron is caused by inherited mutations in TMPRSS6, a liver-expressed gene that encodes a membrane-bound serine protease of previously unknown role that was recently reported to be a regulator of hepcidin expression.

scholarly journals nm1054: a spontaneous, recessive, hypochromic, microcytic anemia mutation in the mouse

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3625-3631 ◽  
Author(s):  
Robert S. Ohgami ◽  
Dean R. Campagna ◽  
Brendan Antiochos ◽  
Emily B. Wood ◽  
John J. Sharp ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Uptake ◽  
Genetic Locus ◽  
Failure To Thrive ◽  
Microcytic Anemia ◽  
Zinc Protoporphyrin ◽  
Hematopoietic Stem ◽  
Hypochromic Microcytic Anemia ◽  
Iron Deficient ◽  
Sparse Hair

AbstractHypochromic, microcytic anemias are typically the result of inadequate hemoglobin production because of globin defects or iron deficiency. Here, we describe the phenotypic characteristics and pathogenesis of a new recessive, hypochromic, microcytic anemia mouse mutant, nm1054. Although the mutation nm1054 is pleiotropic, also resulting in sparse hair, male infertility, failure to thrive, and hydrocephaly, the anemia is the focus of this study. Hematologic analysis reveals a moderately severe, congenital, hypochromic, microcytic anemia, with an elevated red cell zinc protoporphyrin, consistent with functional erythroid iron deficiency. However, serum and tissue iron analyses show that nm1054 animals are not systemically iron deficient. From hematopoietic stem cell transplantation and iron uptake studies in nm1054 reticulocytes, we provide evidence that the nm1054 anemia is due to an intrinsic hematopoietic defect resulting in inefficient transferrin-dependent iron uptake by erythroid precursors. Linkage studies demonstrate that nm1054 maps to a genetic locus not previously implicated in microcytic anemia or iron phenotypes.

Differential Diagnosis of Hypochromic Microcytic Anemia

1980 ◽  
Vol 1 (7) ◽  
pp. 196-222
Keyword(s):  
Iron Deficiency ◽  
Lead Poisoning ◽  
Microcytic Anemia ◽  
Beta Thalassemia ◽  
Age Group ◽  
Peak Incidence ◽  
Hypochromic Microcytic Anemia ◽  
Alpha Thalassemia ◽  
History Of ◽  
Thalassemia Trait

The only hypochromic microcytic anemias in young children are iron deficiency, lead poisoning, and thalassemia. Clinical features helpful in the diagnosis include the following. Iron deficiency: peak incidence from 1 to 2 years of age, diet deficient in iron, or ingestion of more than one quart of milk per day. Alpha-thalassemia trait: occurs in any age group and predominantly in Oriental, black, and Mediterranean races. Beta-thalassemia trait occurs in children more than 6 months of age and predominately in black and Mediterranean races. Lead poisoning: peak incidence from 6 months to 4 years of age and a history of pica. It occurs largely in urban children.

scholarly journals Hepcidin induction by transgenic overexpression of Hfe does not require the Hfe cytoplasmic tail, but does require hemojuvelin

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5679-5687 ◽  
Author(s):  
Paul J. Schmidt ◽  
Nancy C. Andrews ◽  
Mark D. Fleming
Keyword(s):  
Iron Deficiency ◽  
Hereditary Hemochromatosis ◽  
Cytoplasmic Domain ◽  
Microcytic Anemia ◽  
Structural Basis ◽  
Mouse Strains ◽  
Protein Overexpression ◽  
Hepcidin Expression ◽  
Hypochromic Microcytic Anemia ◽  
High Level

Abstract Mutations in HFE cause the most common form of hereditary hemochromatosis (HH). We previously showed that liver-specific, transgenic overexpression of murine Hfe stimulates production of the iron regulatory hormone hepcidin. Here, we developed several additional transgenic mouse strains to further interrogate the structural basis of HFE function in the pathophysiology of HH. We hypothesized that the small, cytoplasmic domain of HFE might be necessary for HFE-mediated induction of hepcidin. We demonstrate that, like the full-length protein, overexpression of Hfe proteins lacking the cytoplasmic domain leads to hepcidin induction, iron deficiency and a hypochromic, microcytic anemia. However, high-level expression of a liver-specific Hfe transgene carrying the mouse equivalent of the common HFE C282Y human disease-causing mutation (murine C294Y) did not cause iron deficiency. Furthermore, hepcidin induction by transgenes encoding both WT Hfe and Hfe lacking its cytoplasmic domain is greatly attenuated in the absence of hemojuvelin (Hjv). Our observations indicate that the extracellular and transmembrane domains of Hfe are sufficient, and Hjv is essential, for Hfe-mediated induction of hepcidin expression.

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

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 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

Abstract 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.

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