Iron Deficiency Anemia - Research Papers

Melkam Tesfaye,1 Tilahun Yemane,2 Wondimagegn Adisu,2 Yaregal Asres,2 Lealem Gedefaw,2

1Department of Clinical Laboratory, Bonga Hospital, Bonga, 2Department of Medical Laboratory Science and Pathology, College of Health Sciences, Jimma University, Jimma, Ethiopia
 
Background: Adolescence is the period of most rapid growth second to childhood. The physical and physiological changes that occur in adolescents place a great demand on their nutritional requirements and make them more vulnerable to anemia. Anemia in the adolescence causes reduced physical and mental capacity and diminished concentration in work and educational performance, and also poses a major threat to future safe motherhood in girls. The purpose of this study was to determine the prevalence of anemia and its associated factors among school adolescents in Bonga Town, southwest Ethiopia.
Methods: A cross-sectional study was conducted among 408 school adolescents in Bonga Town, southwest Ethiopia, from March 15, 2014 to May 25, 2014. An interviewer-administered questionnaire was used to collect sociodemographic and other data. A total of 7 mL of venous blood and 4 g of stool samples were collected from each study participant. Blood and stool samples were analyzed for hematological and parasitological analyses, respectively. Data were analyzed using SPSS Version 20 software for Windows.
Results: The overall prevalence of anemia was 15.2% (62/408), of which 83.9% comprised mild anemia. The proportion of microcytic, hypochromic anemia was 53% (33/62). Being female (adjusted odds ratio [AOR] =3.04, 95% confidence interval (CI) =1.41–6.57), household size ≥5 (AOR =2.58, 95% CI =1.11–5.96), father's illiteracy (AOR =9.03, 95% CI =4.29–18.87), intestinal parasitic infection (AOR =5.37, 95% CI =2.65–10.87), and low body mass index (AOR =2.54, 95% CI =1.17–5.51) were identified as determinants of anemia among school adolescents.
Conclusion: This study showed that anemia was a mild public health problem in this population. School-based interventions on identified associated factors are important to reduce the burden of anemia among school adolescents.

Keywords: anemia, school adolescents, associated factors, Bonga Town

Introduction

Anemia is a condition characterized by reduction in the number of red blood cells and/or hemoglobin (Hb) concentration.1 Anemia is a global public health problem affecting both developing and developed countries and has major consequences for human health as well as social and economic development. It affects 24.8% of the world population.2 The burden of anemia varies with a person’s age, sex, altitude, and pregnancy.1 The worldwide prevalence of anemia among adolescents is 15% (27% in developing countries and 6% in developed countries).3 In Ethiopia, the prevalence of anemia among the age group of 15–19-year-old males and females ranged from 2.8% to 15% and 9.3% to 34.8%, respectively.4

Causes of anemia in developing countries are multi-factorial, which include nutritional (iron, folate, and vitamin B12) deficiencies, infections (such as malaria and intestinal parasitic infection [IPI]), and chronic illness.5 Iron deficiency anemia is a condition in which anemia occurs due to lack of available iron to support normal red cell production.6 The prevalence of iron deficiency and subsequent anemia increases at the start of adolescence. In girls, this is caused by increased requirements of nutrition for growth, exacerbated a few years later by the onset of menstruation, but subsides for boys.7 The physical and physiological changes that occur in adolescents place a great demand on their nutritional requirements and make them more vulnerable to nutritional deficiencies. Adolescents are at high risk of iron deficiency and anemia. This is due to rapid pubertal growth with sharp increase in lean body mass, blood volume, and red cell mass, which increases iron requirements for myoglobin in muscles and Hb in the blood. Iron requirement increases two- to threefolds from a preadolescent level of ~0.7–0.9 mg iron/day to as much as 1.37–1.88 mg iron/day in adolescent boys and 1.40–3.27 mg iron/day in adolescent girls.7,8 Anemia in adolescence has serious implications for a wide range of outcomes, and nearly all of the functional consequences of iron deficiency are strongly related to the severity of anemia. It causes reduced resistance to infection, impaired physical growth and mental development, and reduced physical fitness, work capacity, and school performance.7,9–11

Interventions to reduce the burden of anemia and iron deficiency anemia should address the causatives. Cost-effective anemia prevention and control strategies are well-documented and have the power for their intended objectives in different countries.2,11,12 Knowledge of the degree and causes of anemia in adolescence is important, as this is a window of opportunity for school-based interventions to improve adolescent health. There is a scarcity of data on anemia in adolescents living in developing countries in the complex ecologic context of poverty, parasitism, and malnutrition. At all levels, the negative effects of anemia during adolescence justify public health action; unfortunately, because initiatives to prevent anemia commonly target infants, young children, and pregnant and lactating women, and not necessarily adolescents, the needs of adolescents may remain unmet and the consequences of anemia in adolescents continue. But limited data are available on the prevalence of anemia, iron deficiency, and associated factors among adolescents in Ethiopia, particularly in Bonga Town.

Therefore, this study was aimed to determine the prevalence of anemia, iron deficiency, and associated factors among school adolescents in Bonga Town, southwest Ethiopia.

Materials and methods

Study area and population

An institution-based cross-sectional study was conducted among school adolescents in Bonga Town from March 15, 2014 to May 25, 2014. Bonga Town, a town in the Kaffa Zone, is located 466 km southwest of the capital city, Addis Ababa. It has an average altitude of 1,714 m above the sea level. The total population of Bonga Town was 28,960, which comprised 14,906 females and 14,054.4 Nineteen percent of the total population was adolescents. There were nine governmental schools in Bonga Town administration (three primary, four primary and secondary, and two secondary schools) with a total number of 7,520 students; 5,393 were within the age group of 12–19 years.

Sample size and sampling technique

The sample size was determined using the single population proportion statistical formula (n= z(1−α/2)2×P(1−p)/d2). We used 50% prevalence of anemia among the group because there was no report in the study area, 5% marginal error, and 95% confidence level, and 10% anticipated non-response rate were considered. The final minimum sample size for the study was 422. We included adolescents between 12 years and 19 years who voluntarily participated in the study and excluded school adolescents who had been blood transfused prior to 4 months of data collection, who were on treatments for anemia, and who were pregnant and lactating. Female school adolescents who were married but not using contraceptives and, at the same time, not confirmed for their pregnancy were requested to undergo the urine human chorionic gonadotropin test.

Among eight governmental schools in Bonga Town (Kenteri, Umiti, Millennium, Sheta, Bandra, Barta, B/Mariam, and Bishaw Woldeyohanis), the first three were not included, since all students were <12 years of age. From a total of 7,520 students in Bonga Town enrolled for the academic year 2013/2014, 5,393 were adolescents, all in five schools, of which 1,013 were in Bishaw Woldeyohanis Preparatory School, 758 in B/Mariam Secondary School, 1,875 in Bandra Primary and Secondary School, 1,125 in Sheta Primary and Secondary School, and 622 in Barta Primary and Secondary School. Study participants were selected using a systematic random sampling technique, using each school student’s registration details for the academic year as a sampling frame, which included name, age, and sex. The sequence of schools from the first to the last was followed by using a lottery method as Bandra, Sheta, B/Mariam, Bishaw Woldeyohanis, and Barta, respectively. Sampling was started from the first grade in all the schools purposively. The constant K was determined by dividing the total study population by the sample size (K=5,393/422=12.7). The fifth adolescent student was selected by using a lottery method. The first study participant was the fifth adolescent student in Bandra School, and consecutive study participants were selected at every thirteenth interval.

Data collection methods and instruments

Questionnaire-based interview and anthropometric measurement

Sociodemographic, socioeconomic, and clinical data were collected by trained clinical nurses by using an interviewer-administered questionnaire. Weight and height were taken for each study participant. Height was measured to the nearest 0.1 cm, and weight to the nearest 0.1 kg. Each subject was weighed with light clothing and no foot wear. All the measurements were taken twice; when necessary, any discrepancies were resolved by a third measurement. The mean values were used for data analysis.

Blood collection and analysis

A total of 4 mL of anticoagulated ethylenediaminetetraacetic acid and 3 mL of nonanticoagulated venous blood sample were collected from each study participant using a vacutainer system. Then the samples were transported to the Bonga Hospital laboratory within 2 hours of collection. We determined Hb concentration, mean corpuscular hemoglobin (MCH), MCH concentration, and mean corpuscular volume using CELL-DYN®1800 (Abbott Laboratories, Abbott Park, IL, USA). We prepared both thick and thin blood films for the assessment of hemoparasites and evaluation of red cell morphology. Serum iron was measured by the chromazurol B method13 by using a Humaster 80 Chemistry analyzer (Human Diagnostics, Wiesbaden, Germany). Female adolescents older than 12 years and males in the age group of 12–14 years who had an Hb concentration <12 g/dL and males older than 15 years who had an Hb concentration <13 g/dL were considered as anemic. Hb values of 11–11.9 g/dL, 8–10.9 g/dL, and <8 g/dL were categorized as having mild, moderate, and severe anemia, respectively; however, for male adolescents older than 15 years, Hb concentration of 11.0–12.9 g/dL indicated mild anemia.1 Microcytosis was defined as a mean corpuscular volume value <80 fL, and hypochromia was defined as MCH concentration value <32 g/dL. Iron deficiency was defined as a serum iron concentration <59 μg/L for males and <37 μg/L for females.13 A body mass index (BMI) <18.5 kg/m2 indicates thinness or acute under nutrition, while a BMI >25.0 kg/m2 indicates overweight.

Parasitological survey

Four grams of stool sample was collected from each study participant using clean, wide mouthed, and leak-proof stool cups. Then, we examined stool samples at the data collection site within 10–15 minutes of collection by wet mount preparation. Leftover samples were preserved using 10% formalin as a preservative and transported to the Bonga Hospital laboratory, where we processed for the formol-ether concentration technique. Both thick and thin blood films were examined for the assessment of hemoparasites.

Quality assurance

To ensure the quality of data, data collectors were trained and the questionnaire was pretested. All laboratory activities were performed by strictly following manufacturers’ instructions and specific standard operating procedures. Quality control samples were used accordingly. All reagents and quality control samples were checked for their expiry date. Laboratory results were recorded on standard report formats according to a unique identification number.

Ethical consideration

Ethical clearance was obtained from the Jimma University Ethics Review Committee, College of Health Sciences. Permission to conduct the study was obtained from each school director’s office. We explained the objectives of the study to each study participant. We obtained written informed consent from 18-year- to 19-year-old study participants and from guardians of <18-year-old study participants. In addition, there was an assent section of the consent form for study participants aged <18 years old. The blood and stool specimens were used only for the intended purpose, and leftover specimens were discarded according to the national guidelines. All the data were kept confidential, and this was done using a unique code number. Participants confirmed as anemic and having an IPI were treated under the consultation of physicians.

Statistical analysis

BMI was calculated as weight in kilograms divided by the square of height in meters using Microsoft Office Excel 2007. Adjusted Hb concentration was calculated as Hb =−0.32× (altitude in meters ×0.0033) +0.22× (altitude in meters ×0.0033)2 to subtract the adjustment from the measured Hb concentration at the relevant altitude (1,714 m above the sea level) to get the sea-level value. Then all data were entered, cleaned, and analyzed using SPSS for Windows Version 20.0 statistical package. Descriptive statistics were used to give a clear picture of background information and determine the prevalence of anemia. Binary logistic regressions were used to identify the candidate variables for multiple logistic regression analysis. All explanatory variables that have been associated with the outcome variable in bivariate analyses at a 25% level of significance were considered as candidates for backward multiple logistic regression analysis. All variables with P-values <0.05 were considered as statistically significant.

Results

Sociodemographic and clinical characteristics of study participants

From the total sample size (422), 408 school adolescents were enrolled in the study (96.7% response rate). Most of the study participants were within the age group of 15–19 years, 67.2% (n=274). The mean age of the study participants was 15±2 years. The male to female ratio of the study participant was 0.85:1; the females accounted 54.2% (n=221). The majority of the study participants’ mothers were house wives, 42.4% (n=173). The family size of study participants ranged from 2 to 11, with an average of 5.8 persons per household, and most of the study participants had a household size of >5 (Table 1).

Table 1 Association of anemia with sociodemographic and clinical factors among school adolescents from March 15, 2014 to May 25, 2014 (n=408)
Note:aStatistically significant factors.
Abbreviations: COR, crude odds ratio; CI, confidence interval; ETB, Ethiopian Birr; IPI, intestinal parasite infection.

All 408 study participants were examined for intestinal parasites, of whom 32.8% (n=134) showed positive response for at least one intestinal parasite. A total of six species of intestinal parasites were identified. Ascaris lumbricoides (48.4%, n=77) took the predominant proportion followed by Giardia lamblia (20.8%, n=33), Trichuris trichiura (13.2%, n=21), Entamoeba histolytica/dispar (8.8%, n=14), Hook worms (6.3%, n=10), and Hymenolepis nana (2.5%, n=4). A microscopic examination of blood films revealed that no hemoparasite was found.

Dietary and nutritional characteristics of adolescents

Eating habit sources of heme iron and enhancers and inhibitors of iron absorption were assessed among all study participants. The majority, 90.4% (n=369), of the study participants ate meat/poultry less than two times per week and 78.9% (n=322) took citrus fruits less than two times per week. Most of the study participants, 92.2% (n=376), responded that they drink tea/coffee within 30 minutes after meal (Table 1).

Prevalence, severity, and type of anemia

The overall prevalence of anemia was 15.2% (n=62). The prevalence was higher in female (19.3%) than male (9.4%) adolescents. From the overall number of anemic adolescents, 74.2% (n=46) were females, and the prevalence of anemia among females who attained menarche was 26.4% (Table 2). Most of the anemic adolescents had mild anemia (83.9%), followed by moderate (12.9%) and severe anemia (3.2%). From the total number of anemic adolescents, 53% (n=33), 40% (n=25), and 7% (n=4) had microcytic hypochromic, normocytic normochromic, and macrocytic normochromic anemia, respectively. More than 72% of anemic adolescents had low serum iron concentration (Figure 1).

Table 2 Association of anemia with nutritional and reproductive health-related factors among school adolescents in southwest Ethiopia from March 15, 2014 to May 25, 2014
Notes:aStatistically significant factor; bP-value for Fisher’s exact test.
Abbreviations: COR, crude odds ratio; CI, confidence interval.

Figure 1 Serum iron concentration among anemic school adolescents in southwest Ethiopia, from March 15, 2014 to May 25, 2014.

Independent predictors of anemia among study participants

Six explanatory candidate variables from backward multiple logistic regression analysis were found to be independent predictors of anemia among school adolescents. Their corresponding adjusted odds ratios are presented in Table 3.

Table 3 Independent predictors of anemia from a multivariate logistic regression model among school adolescents in southwest Ethiopia from March 15, 2014 to May 25, 2014 (n=408)
Note:aStatistically significant factor.
Abbreviations: AOR, adjusted odds ratio; CI, confidence interval; IPI, intestinal parasitic infection.

Discussion

The aim of this study was to determine the prevalence of anemia and associated factors of anemia among school adolescents in Bong Town, southwest Ethiopia. Four hundred and eight randomly selected representative school adolescents were involved in this study. Approximately, one in six school adolescents were anemic in our study. The overall prevalence of anemia was 15.2%, indicating mild public health importance. This showed that anemia was indeed a public health problem among the adolescents in the area. Multivariate analysis identified sex, family size, father’s educational status, IPI, and BMI as predictors of anemia among adolescents in this study.

The 2011 Ethiopia Demographic and Health Survey reported that the prevalence of anemia among adolescents in the age range of 15–19 years was 13.4%. For the same age group, the prevalence of anemia was 9.4% in Southern Nation’s Nationalities and Peoples Region of Ethiopia.4 This variation might be due to the difference in the study population that a larger age range of study participants (12–19 years) were included in this study. The prevalence of anemia in this study was higher than studies among adolescents in Turkey (5.6%)3 and in Shimla, India (13.1%).14 This variation might be due to age group differences as 12–16-year- and 10–19-year-old adolescents were included in these two studies, respectively. The other reason might be due to the high prevalence of IPI in our study, difference in Hb cutoff value, and study population.

However, prevalence of anemia in this study was much lower than studies conducted in Nepal (65%), Wardha (59.8%), and Cote d’Ivoire (53.1%).15–17 The lower prevalence of anemia in this study might be due to the variation in geographical area and study participants. This study was school based and was carried out in an urban population, which might decrease the prevalence in this study.

It was indicated that among anemic adolescents, the proportion of mild anemia was high (83.9%), followed by moderate anemia (12.9%) and severe anemia (3.2%). This finding was in parallel with studies done in Pondicherry18 and Shimla of India19 and IBSY (Indira Bal Swasthya Yojna) of northern India.20 However, our study is different from the study performed in Eastern Sudan where 66.8% had moderate anemia and 12.1% had severe anemia.21 The reason for this variation might be increased nutritional deficiency and difference in study participants. The study in Eastern Sudan reported increased deficiency of micronutrients, such as iron, folate, copper, and zinc, which contributed to the etiology of anemia, and the study participants were mainly adolescent girls. Using altitude-adjusted Hb concentration in our study might be the other reason for this variation.

From the anemic adolescents, more than half of them had microcytic hypochromic anemia (53%), followed by normocytic normochromic anemia (40%) and macrocytic normochromic anemia (7%). The reason for the high percentage of microcytic hypochromic anemia might be due to iron deficiency in adolescents because of rapid growth, hormonal change, and starting of menstrual period in girls. Our study findings indicated that female adolescents were 3.04 times more likely to be anemic than male adolescents. This finding was in line with similar studies carried out in Turkey3 and among Black and Spanish American adolescents.12 Scientific evidence suggests that physical and physiological changes that occur in adolescent girls place a great demand on their nutritional requirements and make them more vulnerable to nutritional deficiencies. Specifically, the increase in the lean body mass, the expansion of the total blood volume, and the onset of menstruation translate into a significant increase in girls’ iron requirements, making them more susceptible to anemia.22

Fathers’ educational status was significantly associated with the prevalence of anemia among school adolescents in this study. School adolescents who had illiterate fathers were 9.03 times more likely to be anemic as compared to school adolescents who had fathers who were literate above the secondary level. This might be due to the reason that a father who is educated is able to make informed decisions about his own family and so for his child as compared to his illiterate counterpart. This is because, in Ethiopia, most of the family’s decisions are made by the father and when they are educated, they might have the power to make decisions in matters related to adolescent health and the expected expenses, which had an effect on the anemia prevalence. On the other side, the reason might be that educated fathers are more likely to have well-paid jobs and are also more likely to adopt a healthier dietary behavior.

This study also showed that the prevalence of anemia among school adolescents who had been infected with intestinal parasites was significantly higher compared to those noninfected with intestinal parasites. This is in line with a previous similar study.23 This might be due to the fact that most identified intestinal parasites have their own contribution on blood loss and/or red cell destruction.

In our study, family size was significantly associated with anemia among school adolescents. School adolescents who had family size of five and more were 2.58 times more likely to be anemic as compared with school adolescents from a family size of less than five. This might be due to the reason that the large size of the family can be related with low care per family member and income constraint to obtain diets with a variety of foods rich in micronutrients such as iron. Our study revealed that the nutritional status was significantly associated with anemia. Undernourished school adolescents who had a low BMI <18.5 kg/m2 were 2.54 times more likely to have anemia as compared to those who have a BMI ≥18.5 kg/m2. Although literature indicated that there was an association between the prevalence of anemia among female adolescents with frequency of meat consumption,24 no statistical significant association between dietary habits and prevalence of anemia was observed in this study. This could be possibly due to the fact that dietary history was obtained by using 24 hours recall method that was not adequate to bring out the true association between dietary intake and prevalence of anemia. The associations between anemia and malaria, which have been observed in similar studies, were not demonstrated in our study. This was due to the low prevalence in the area and no malaria parasite infection identified in our study.

Although our study tried to determine the prevalence of anemia, serum iron concentrations, and associated factors among school adolescents, it was not without limitation. Owing to the cross-sectional study design used, whether anemia preceded the predisposing factors or the vice versa could not be verified in this study. The level of serum ferritin was not measured in this study, which limits further determination of the prevalence of iron deficiency anemia.

Conclusion

According to the World Health Organization,2 anemia in this study can be considered of mild public health significance; indeed, it was a public health problem among school adolescents in the area. School-based intervention among school adolescents based on identified determinant factors will be very important for the prevention and control of anemia among the group.

Acknowledgments

The authors would like to thank study participants who provided all relevant information for the study and also biological samples as volunteers. We also extend our gratitude to the data collectors for their efforts.

Author contributions

MT, WA, LG, and TY conceived the study, participated in the design and data analysis. MT and YA were involved in data acquisition and laboratory work. All authors contributed towards data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work. All the authors read and approved the manuscript.

Disclosure

The authors report no conflicts of interest in this work.


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Iron Deficiency Anaemia: A Short Review

Salma AlDallal1,2*

1Haematology Laboratory Specialist, Amiri Hospital, Kuwait

2Faculty of biology and medicine, health, The University of Manchester, UK

Corresponding Author:
Salma AlDallal
Haematology Laboratory
Specialist, Amiri Hospital, Kuwait
Tel: +96590981981
E-mail: [email protected]

Received date: August 18, 2016; Accepted date: September 07, 2016; Published date: September 09, 2016

Citation: AlDallal S (2016) Iron Deficiency Anaemia: A Short Review. J Immunooncol 2:106.

Copyright: © 2016 AlDallal S. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract

Iron deficiency anaemia (IDA) is one of the most widespread nutritional deficiency and accounts for almost onehalf of anaemia cases. It is prevalent in many countries of the developing world and accounts to five per cent (American women) and two per cent (American men). In most cases, this deficiency disorder may be diagnosed through full blood analysis (complete blood count) and high levels of serum ferritin. IDA may occur due to the physiological demands in growing children, adolescents and pregnant women may also lead to IDA. However, the underlying cause should be sought in case of all patients. To exclude a source of gastrointestinal bleeding medical procedure like gastroscopy/colonoscopy is utilized to evaluate the level of iron deficiency in patients without a clear physiological explanation. Inevitably, the accurate management of this disorder improves the quality of life, improves the symptoms of iron deficiency, and lessens the requirement for blood transfusion. The treatment options include oral iron supplement and intravenous iron therapy. However, this mode of treatment is not tolerable by some patients while it is insufficient in a certain subset of patients. Therefore, intravenous iron supplementation is considered undesirable approach and there is not much clarity on the safety concerns associated with this approach in case of very high doses or in the presence of very high ferritin levels. In addition, red cell transfusion is not recommended for IDA unless there is a need for immediate action. The objective of the review is to provide a critical summary and an update of the diagnosis and treatment options of IDA.

Keywords

Iron deficiency anaemia; Gastrointestinal; Insufficient iron intake; Microcytic

Introduction

Anaemia can be defined by a condition in which the total haemoglobin (Hb) level or number of red blood cells (RBCs) is poorly lowered. The World Health Organisation (WHO) defines anaemia as Hb<130 g/L in men older than 15 years, 110 g/L in pregnant women, and <120 g/L in non-pregnant women older than age 15 years [1]. Table 1 shows the definition of anaemia as defined by the World Health Organization (WHO) Iron deficiency anaemia (IDA) is a certain anaemic condition arising due to the inadequate iron to form normal RBCs. IDA is usually caused by insufficient iron intake, chronic blood loss, and increased iron demand [2]. The prevalence of IDA varies across the world [3]. Recognizing the original aetiology and the relevant diagnostic and therapeutic issues are primary keys in the management and assessment of this disorder.

PopulationHb Diagnostic of anaemia (g/dL)a
Children aged 6 months to 6 years old<11.0
Children aged 6-14 years old<12.0
Adult men<13.0
Adult non-pregnant women<12.0
Adult pregnant women<11.0

Table 1: World health organization definition of anaemia. aValues obtained from venous blood samples obtained at sea level.

Iron is an important dietary mineral associated with many body functions like oxygen transport in the blood. Iron deficiency anaemia is characterized by incomplete haemoglobin synthesis that results in microcytic and hypochromic red blood cells. Due to inadequate haemoglobin, the ability of blood to deliver oxygen to the other body cells and tissues is reduced [4-7].

Iron deficiency is defined as an imbalance of iron intake, absorption and iron loss. The iron deficiency is the first cause of anaemia. Pallor, fatigue and dyspnea are the most common symptoms of anaemia. Anaemia is classically associated with microcytosis and hypochromia in biological exams. Iron deficiency, inflammatory aetiologies, thalassemia and sideroblasticanaemia are the origins of microcytic anaemia [4-8].

Iron metabolism

Iron is an essential element required for the maintenance of physicochemical processes. It is very much necessary to maintain its balance for proper physiologic functioning in the body. As the overabundance of iron can have extreme adverse effects like liver swelling and damage, in the same manner it is always advisable to avoid iron deficiency (ID) or iron overload [9,10]. The body absorbs 1 to 2 mg of dietary iron a day, which is balanced through body processes i.e., menstruation, sloughed intestinal mucosal cells, and other blood losses [11]. Dietary iron comprises heme iron (animal sources) and non-heme iron (vegetable and cereal sources). Heme iron bound to Hb and myoglobin is responsible for delivering oxygen to the tissues. Pancreatic enzymes digest heme to release it from the globin molecule in the intestinal lumen. This is followed by the absorption of heme iron into the enterocytes as metalloporphyrin takes place and it is further degraded by heme oxygenase-1 leading to the release of non-heme iron. Subsequently, iron is exported by the only iron exporter ferroportin, present on the basolateral aspect of the enterocyte [12]. On the other hand, non-heme iron is less well absorbed. It is absorbed by intestinal luminal cells through a specific transporter and released into the circulation wherein the binding of transferrin occurs. Transferrin receptors on erythroblasts accept iron-transferrin complexes, which undergo the process of endocytosis leading to the incorporation of iron into Hb [13,14].

Iron absorption is maintained by increased erythropoiesis and iron deficiency, and down-regulated in iron repletion and inflammation. This dynamic process of iron absorption is mediated by hepcidin, which regulates the inflow of iron and blocks iron release from enterocytes and macrophages [15]. Iron stores in the body are regulated through the process of iron absorption. Non-heme iron is absorbed in the ferrous form (Fe+2). Reduction of ferric iron (Fe+3) by dietary ascorbic acid, stomach acidity, and luminal reductase improves the iron absorption. Non-heme iron is repressed by simultaneous consumption of tannins (in tea), phytic acid (in cereal and legumes), and calcium. Simultaneous consumption of ascorbic acid and heme iron sources also improves the process of absorption [14-16].

Symptoms of IDA

The two main types of iron deficiency are 1) absolute iron deficiency arising due to the lowered or exhausted level of total body iron stores are low or exhausted and, 2) functional iron deficiency wherein the total body iron stores are normal or increased, with the insufficient iron supply to the bone marrow. Absolute iron deficiency and functional iron deficiency can coexist. Functional iron deficiency is present in many acute and chronic inflammatory states [17].

The clinical features of iron deficiency anaemia depends on the following factors:

• Level of severity of the anaemia

• Age group

• Multiple disorders

• Illness consistency

• Speed of onset

Patients with iron deficiency anaemia present with symptoms that are associated with all anaemias such as pallor of the skin, conjunctivae, nail beds, fatigue, vertigo, syncope, exertional dyspnoea progressing to breathlessness at rest, tachycardia headache, and a cardiac systolic flow murmur [17-22]. The patients may also show dyspnoea at rest angina pectoris and haemodynamic instability in severe cases [21].

Iron deficiency rapidly affects the epithelial cells thereby leading to dryness and roughness of the skin, dry and damaged hair, koilonychias and alopecia. In mild-to-moderate iron deficiency loss of tongue papillaeis reported. Atrophic glossitis is also noted in severe cases. Iron deficiency may be associated with restless legs syndrome [23].

Anaemic condition tends to have negative impact physical performance, mostly work productivity due to reduced oxygen transport the reduced cellular oxidative capacity [13]. Perinatal iron deficiency is associated with tardy neurocognitive development and psychiatric illness [3,9-14,24,25]. Various symptoms associated with anaemia are listed in Table 2.

Very frequentFrequentRare
·Dimness or Paleness·Diffuse and moderate alopecia·Haemodynamic instability
·Exhaustion and tiredness·Atrophic glossitis·Syncope
·Dyspnoea·Restless legs syndrome·Koilonychia
·Headache·Dry and rough skin·Plummer-Vinson syndrome
 ·Dry and damaged hair 
·Cardiac murmur
·Tachycardia
·Neurocognitive dysfunction
·Angina pectoris
·Vertigo

Table 2: Symptoms of iron deficiency anaemia.

Common causes of anaemia

Regardless of the various aetiologies, most anaemic patients usually have some component of iron deficiency, which responds to iron administration. With the elderly, the aetiology is attributed to iron deficiency in approximately one-third and chronic renal disease or inflammation accounts to another one-third. The aetiology in the remaining group is often unclear [26,27]. Latrogenic anaemia or druginduced immune hemolytic anaemia (DIIHA) should be underscored with a growing list of commonly used medications being implicated [27]. Furthermore, data on blood loss due to excessive diagnostic phlebotomy in hospitalized patients have also been a cause of major concern [28].

Diagnosis of IDA

IDA diagnosis necessitates the laboratory investigation. IDA should not be presumed unless confirmed by laboratory testing in addition to evidence of low iron stores [29]. Further, iron deficiency should be distinguished from the other causes of anaemia owing to its associations with the underlying disorders that necessitate particular investigation while the treatment for this is simple, safe and effective [30]. The initial examination of anaemia follows a simple process widely used in haematology [31]. The evaluation of the primary reason for anaemia includes a complete blood count (CBC), peripheral blood smear, reticulocyte count, and serum iron indices. A CBC can be helpful in determining the mean corpuscular volume (MCV), which measures the average size of RBCs, and mean corpuscular haemoglobin concentration, which measures the concentration of haemoglobin in a given amount of packed RBCs. The common characteristics of IDA include hypochromic RBCs, microcytic, and low iron stores. Although microcytic anaemia is characterized by small red blood cells and iron deficiency, up to 40% of patients with IDA have normocytic RBCs [12,27]. Other reasons of microcytic anaemia include chronic inflammatory diseases, thalassaemia, lead poisoning, and sediroblastic anaemia [32]. The red cell distribution width (RDW) is a measure used in combination with the MCV to differentiate between mixed causes for anaemia from that of a single cause. An elevated RDW value signifies a variation in the size of the red blood cell. In addition, RDW may also be elevated at the early stages of IDA and folate with or without the deficiency of vitamin B12, both of which cause macrocytic anaemia [12,33]. White blood cell (WBCs) and platelet counts help to distinguish isolated anaemia from pancytopenia [31].

Patients suspected to have IDA should undergo iron studies test. The results determined from this test should be correlated with the red cell indices. The serum ferritin level is the most commonly available and useful index of iron deficiency [30]. Iron studies diagnostic for IDA consists of low haemoglobin (<13 g/dL and 12 g/dl in women), low transferrin saturation (<15%), a low serum ferritin (<30 μg/L), and high total iron-binding capacity (>13.1 μmol/l) [34,35]. However, one point to be noted is that ferritin is also an acute-phase protein and tends to be elevated in cases of infection, liver disease, inflammation, and malignancy. This can result in misleadingly elevated ferritin levels in iron-deficient patients with co-excising systemic illness [16,34]. Other markers such as C-reactive protein (CRP) may also help identify coexisting inflammation in cases of an underlying inflammation or infection [36,37]. Serum iron levels have significant diurnal variation, they tend to be low in both inflammation and IDA, and should not be used as a mode of diagnosis for iron deficiency [30].

Soluble transferrin receptor (sTfR) level is considered an additional iron index is the, which acts as a parameter for the diagnosis of IDA and as an indirect measure of erythropoiesis. It tends to be increased in patients with ID [38]. Another additional advantage of this test is that the soluble transferrin receptor level remains unaffected by inflammatory states and helps recognize concomitant IDA in patients with anaemia of chronic disease (ACD) [39].

If the other tests don’t prove helpful and suspicion for IDA still persists, the absence of stainable iron in a bone marrow biopsy can be considered as the standard diagnostic measure [40].

As mentioned above, the diagnostic accuracy of ferritin is limited as it behaves as an acute phase reactant. The level of serum ferritin is often elevated independent of iron status by factors such as acute or chronic inflammation, infection, malignancy, liver disease, and alcohol use. Also, the levels of serum iron is reduced with infection, inflammation, and malignancy and elevated with liver disease [30]. On the other hand, past studies showed that the measurement of reticulocyte haemoglobin content (CHr) is identified as an indirect measure of the functional iron available for new RBC production [41]. In a study done by Mast et al. showed that CHr of <28 pg had an optimal sensitivity (74%) and specificity (73%) for diagnosis of IDA, using Prussian blue staining of the Bone Marrow (BM) aspirate to define iron deficiency [42]. Furthermore, Thomas et al. reported that functional iron deficiency was defined as CHr <28 pg. Therefore, CHr in combination with other parameters proves to be highly useful and reliable in the safe diagnosis of IDA [34].

If these tests are indicative of IDA, then iron therapy should be advised. Recommendation of additional evaluation of possible underlying causes of blood loss should also be considered for the patients with IDA. The British Society of Gastroenterology guidelines puts forward the best practice for upper and lower gastrointestinal (GI) study in all men and postmenopausal women with IDA and no history of clear blood loss from sources other than GI tract and offer an system to use various diagnostic measures [43].

Complication of IDA

Various physiological and pathological conditions promote iron deficiency anaemia. Blood loss, malabsorption, iron deficiencies are some complications associated with anaemia. Iron deficiency anaemia is frequently reported in chronic disorders [44], including inflammatory bowel diseases (IBD), [19,45] chronic kidney disease [46], chronic heart failure cancer and rheumatoid arthritis obesity [17,29,47]. Pathological disorders associated with iron deficiency anaemia are listed in Table 3.

Blood lossMalabsorptionIDA associated with anaemia of chronic diseaseGenetic disorders
•Digestive tract: colonic carcinoma, gastric carcinoma, inflammatory bowel
•Diseases, ulcers, angiodysplasia, parasites
•Gynaecological loss
•Surgery
•Haematuria, epistaxis, haemoptysis
•Haemodialysis
•Non-steroidal anti-inflammatory drugs, aspirin
•Coeliac disease
•Gastrectomy
Helicobacter pylori
•Gut resection, atrophic gastritis, bypass gastric surgery, bacterial overgrowth
•Interaction with food elements: tea, coffee, calcium, flavonoids, oxalates, phytates
•Pica syndrome, pagophagia
•Proton-pump inhibitors and H2 antagonists
•Chronic heart failure
•Cancer50
•Chronic kidney disease
•Rheumatoid arthritis
•Obesity
•Inflammatory bowel diseases
•Iron-refractory iron deficiency anaemia
•Divalent metal transporter deficiency anaemia,
•Fanconianaemia
•Pyruvate kinase deficiency

Table 3: Pathological disorders associated with iron deficiency anaemia.

Prevention of IDA

It is necessary to expand public health initiatives in order to raise awareness and prevent IDA in children ultimately. Clinicians should not rely on traditional stereotypes and should be cautious of the possibility of iron deficiency leading to anaemia in all children [48].

Jaber et al. conducted a study to determine the effect of nutritional education and supplemental iron administration on the prevalence of IDA in Arab infants. A total of 310 infants were randomized into two groups. Mothers in the control group received standard information on prevention of IDA and mothers in intervention group received extensive information on the importance of an iron rich diet and were encouraged to give their children an iron polymaltose complex (IPC) preparation starting from age 4 months to 1 year. Anaemia was recorded in 28% in intervention and 34% in control groups. Frequency of anaemia was lower in infants who received iron medication ≥ 6 months and in infants breastfed for ≥ 6 months. After this study various questions were raised regarding the strategies of preventing iron deficiency anaemia in infancy [49].

The treatment should involve iron replacement in addition to the diagnostic steps that are focussed towards correcting the fundamental cause of iron deficiency anaemia. Oral iron replacement is effective and cheap, but parenteral therapy may be sometimes required due to intolerance, disobedience or failure of treatment via oral therapy. Iron needs are tripled during pregnancy, because of expansion of maternal red cell mass and growth of the fetus and placenta [50].

Severe iron deficiency anaemia is associated with considerable morbidity and is preventable. There are three potentially modifiable feeding practices associated with iron deficiency anaemia that may present opportunities for preventive interventions through primary care as well as public health settings: 1) Cow’s milk intake should be limited to 500 ml/d after 1 year of age, 2) Use of bottle should be discontinued by 12-15 months or earlier, 3) Infants should not be put to sleep with a bottle.

Healthy infants have adequate iron stores until 4-6 months of age, and iron deficiency anaemia peaks between 1 to 3 years of age [43]. Therefore, it is critical to identify optimal feeding practices beyond the first 6 months of life to prevent iron deficiency anaemia. Canadian Paediatric Society, Health Canada, Breastfeeding Committee for Canada and Dieticians of Canada confirm their recommendation of exclusive breast-feeding for the first six months [51,52].

Management of IDA

Once IDA is confirmed, the choice between intravenous and oral forms of iron therapy should be made based on the clinical circumstances on a case-by case basis.

Dietary therapy

Increasing dietary iron consumption alone is insufficient to treat IDA and higher supplemental doses of iron are essential. However, increasing the iron intake and enhancing the absorption by minimising the inhibitors and maximising the enhancers may be valuable for secondary prevention of iron deficiency [30].

Oral iron therapy

The dosage of iron required to treat IDA in adults is 120 mg/day for three months; the dosage for children is 3 mg/kg per day, up to 60 mg/day [32]. In a study done by Baker et al. an increase in haemoglobin of 1 g/dL after one month on treatment showed an adequate response to treatment and confirmed the diagnosis of IDA. In adults with IDA, the treatment should be continuously undergone for three subsequent months after the anaemia is corrected for the replenishment of the iron stores [53].

Physicians often face the challenge of managing IDA with oral iron intake especially when the iron losses in patients exceeds the maximum amount of iron that gut is able to absorb [12]. Additionally, the amount of iron absorbed by the body from GI tract is frequently limited to a few milligrams per day, and consequently, oral iron supplementation may not be able to keep up with the on-going losses. Adherence with oral iron is poor because of frequent GI side effects such as epigastric discomfort, nausea, diarrhoea, and constipation, which limit the usefulness of oral iron [54,55].

Parenteral iron therapy

Parenteral treatment may be used in patients who cannot absorb or tolerate oral iron, such as those who have undergone gastrectomy, bariatric surgery, gastrojejunostomy, or other small bowel surgeries [55]. Parenteral iron therapy can offer a number of clinical advantages, especially newer formulations with better safety profiles in addition to their ability to efficiently restore the body iron stores [56]. The most adverse effect of intravenous therapy includes GI effects, worsening symptoms of inflammatory bowel disease, renal-failure-induced anaemia treated with erythropoietin, unresolved bleeding, and insufficient absorption in patients with celiac disease [57].

Red cell transfusion

Transfusion of red cells is a warranted treatment for severe anaemia [58]. Recommendations often specify certain haemoglobin values as indications to transfuse, but the patient’s clinical condition and symptoms are critical mode of determining whether RBC transfusion should be carried out or not [59]. Transfusion is associated with adverse consequences, including fluid overload, and a range of immunological hazards. Therefore, it should be kept for immediate, targeted management in patients with severe anaemia and end-organ function, or where IDA is complicated by series acute on-going bleeding. Iron treatment must always follow transfusion to restore iron [30].

Conclusion

IDA remains a common and important disorder and accounts for approximately one-half of the cases of anaemia. The diagnosis of anaemia is confirmed by the findings of low iron stores and haemoglobin level below normal. In cases of IDA, oral iron treatment should be initiated for the replenishment of iron stores. Intravenous therapy may also be used in patients who cannot tolerate or absorb oral iron formulations.

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