Microcytic anemia. Differential diagnosis and management of iron deficiency anemia

Microcytic anemia is defined as the presence of small, often hypochromic, red blood cells in a peripheral blood smear and is usually characterized by a low MCV (less than 83 micron 3). Iron deficiency is the most common cause of microcytic anemia. The absence of iron stores in the bone marrow remains the most definitive test for differentiating iron deficiency from the other microcytic states, ie, anemia of chronic disease, thalassemia, and sideroblastic anemia. However, measurement of serum ferritin, iron concentration, transferrin saturation and iron-binding capacity, and, more recently, serum transferrin receptors may obviate proceeding to bone marrow evaluation. The human body maintains iron homeostasis by recycling the majority of its stores. Disruptions in this balance are commonly seen during menstruation, pregnancy, and gastrointestinal bleeding. Although the iron-absorptive capacity is able to increase upon feedback regarding total body iron stores or erythropoietic activity, this physiologic response is minimal. Significant iron loss requires replacement with iron supplements. The vast majority of patients respond effectively to inexpensive and usually well-tolerated oral iron preparations. In the rare circumstances of malabsorption, losses exceeding maximal oral replacement, or true intolerance, parenteral iron dextran is effective. In either form of treatment, it is necessary to replete iron stores in addition to correcting the anemia. [1]

A Mutation In The TMPRSS6 Gene, Encoding A Transmembrane Serine Protease That Suppresses Hepcidin Production, In Familial Iron Deficiency Anemia Refractory To Oral Iron

Background Hepcidin plays a key role in body iron metabolism by preventing the release of iron from macrophages and intestinal cells. Defective hepcidin synthesis causes iron loading, while overproduction results in defective reticuloendothelial iron release and iron absorption.

Design and Methods We studied a Sardinian family in which microcytic anemia due to defective iron absorption and utilization is inherited as a recessive character. Five members showed iron deficiency anemia that was not responsive to oral iron and only partially responsive to parenteral iron administration. To investigate the involvement of known genes implicated in iron metabolism we carried out linkage analysis with microsatellite markers mapping close to these genes. Afterwards, a genome-wide search was performed.

Results No linkage was found between the phenotype of the patients and several known human genes involved in iron metabolism (DMT1, TF, TFRC, ZIRTL, HAMP, HJV). Genome-wide scanning by microsatellites and single nucleotide polymorphisms showed a multipoint LOD score of 5.6 on chromosome 22q12.3–13.1, where the matriptase-2 (also known as transmembrane protease, serine 6 or TMPRSS6) gene is located. Its murine counterpart (Tmprss6) has recently been found to be an essential component of a pathway that detects iron deficiency and suppresses hepcidin production. Sequencing analysis of TMPRSS6 revealed a homozygous causal mutation, predicting a splicing error and a truncated TMPRSS6 protein in affected members. Homozygous subjects had inappropriately elevated levels of serum and urinary hepcidin.

Conclusions The findings of this study suggest that the observed TMPRSS6 mutation leads to overproduction of hepcidin and, in turn, to defective iron absorption and utilization. More generally, they confirm in humans the inhibitory effect of matriptase-2 on hepcidin synthesis already demonstrated in mice. [2]

Brain iron and behavior of rats are not normalized by treatment of iron deficiency anemia during early development

Previous studies in rats have shown that iron deficiency anemia (IDA) during brain development results in lower brain iron concentration and behavioral deficits that persist despite iron treatment after weaning. The present study used a developmental IDA model to determine whether earlier iron treatment might normalize brain iron concentration and behavior. One and one-half week periods of IDA were instituted during early or late gestation or lactation by providing low iron diet to adolescent rat dams and oral iron treatment at the end of the anemia period. The iron deficiency anemia of dams during gestation and lactation resulted in significantly lower pup brain iron concentration at 3 mo of age (15-33% lower than control), despite iron treatment of dams as early as mid-gestation. Dam IDA during lactation lowered pup brain iron concentration significantly more than IDA during gestation (21% lower). All IDA groups had significantly poorer performance and lower activity compared with controls on a screen of home orientation at 8 d of age. Activity on this test was significantly less than controls at 12 d of age. Homing ability on d 12 and 16 and activity on d 16 did not differ from controls. Groups that were anemic around delivery had significant behavioral differences at 3 mo which included less defecation in the open field and greater swim distance in the Morris maze. These results raise the concern that iron sufficiency throughout the course of rain development is crucial to the achievement of normal brain iron concentration and behavior in rats. [3]

Iron Deficiency and Iron Deficiency Anemia in Adolescent Girls in Rural Upper Egypt

Background: Iron deficiency (ID) and iron deficiency anemia (IDA) in adolescents tends to increase with age due to acceleration of growth.

Objectives: This study aimed to determine the prevalence of ID and IDA in adolescent girls in rural Upper Egypt.

Methods: 912 girls in 5 different village preparatory schools situated in El-Minya governorate at Upper Egypt were enrolled in the study. Complete blood count and serum ferritin were done to determine the prevalence of ID and IDA among them.

Results: Our study revealed 39.9% of the girls were anemic, the prevalence of IDA was 30.2% and that of ID without anemia was 11.4%.

Conclusions: ID, with or without anemia is still a major health problem in adolescent girls living in rural Upper Egypt. [4]


Comparison between Ferrous Ascorbate and Colloidal Iron in the Treatment of Iron Deficiency Anemia in Children from Kolkata, India

Aim: To compare the efficacy and safety of ferrous ascorbate and colloidal iron in children with iron deficiency anemia.

Study Design: An open, randomized, comparative, parallel-group study.

Place and Duration of Study: Department of Pediatric Medicine of ‘Nilratan Sircar Medical College and Hospital’, Kolkata, India, between January 2009 and February 2010.

Methodology: Children between the age group of 6 months to 12 years were included if they had anemia defined as hemoglobin <10 gm%. Children received treatment with either ferrous ascorbate or colloidal iron for 12 weeks. Each child received elemental iron 3 mg/kg body weight/day. Follow-up assessments were performed at the end of week 4, week 8 and week 12.

Results: Out of the 137 children screened, 80 were included in the analysis. The mean rise in hemoglobin at the end of the 12 weeks was significantly higher in ferrous ascorbate group than colloidal iron group [3.24 ± 1.66 gm% vs. 1.42 ± 2.04 gm%; p <0.01]. Responder rate (hemoglobin ≥11.5 gm%) after 12 weeks of therapy was 53.57% in ferrous ascorbate group versus 10.34% in colloidal iron group; p<0.01.

Conclusion: The study provides evidence for the role of ferrous ascorbate as an efficient oral iron supplement in the treatment of iron deficiency anemia in children. [5]


[1] Massey, A.C., 1992. Microcytic anemia. Differential diagnosis and management of iron deficiency anemia. The Medical Clinics of North America, 76(3), pp.549-566.

[2] Melis, M.A., Cau, M., Congiu, R., Sole, G., Barella, S., Cao, A., Westerman, M., Cazzola, M. and Galanello, R., 2008. A mutation in the TMPRSS6 gene, encoding a transmembrane serine protease that suppresses hepcidin production, in familial iron deficiency anemia refractory to oral iron. haematologica, 93(10), pp.1473-1479.

[3] Felt, B.T. and Lozoff, B., 1996. Brain iron and behavior of rats are not normalized by treatment of iron deficiency anemia during early development. The Journal of nutrition, 126(3), pp.693-701.

[4] Mohamed Omar Mousa, S., Mahmoud Saleh, S., Mohammed Monir Higazi, A. and Ahmed Abdelnaeem Ali, H. (2016) “Iron Deficiency and Iron Deficiency Anemia in Adolescent Girls in Rural Upper Egypt”, International Blood Research & Reviews, 5(4), pp. 1-6. doi: 10.9734/IBRR/2016/25826.

[5] Ganguly, S., Dewan, B., Philipose, N., Samanta, T., Paul, D. and Purkait, R. (2012) “Comparison between Ferrous Ascorbate and Colloidal Iron in the Treatment of Iron Deficiency Anemia in Children from Kolkata, India”, Journal of Advances in Medicine and Medical Research, 2(2), pp. 195-205. doi: 10.9734/BJMMR/2012/900.

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