Anemia is a widespread public health problem associated with an increased risk of morbidity and mortality, especially in pregnant women and young children (Kraemer & Zimmerman,2007).
Anemia is defined as a condition in which the Hb concentration in peripheral blood is lower than normal for age, sex and pregnancy state of the subject. The Hb is usually directly related to the total red cell volume, with a few exceptional circumstances, namely during the first hours of life when there is hemoconcentration, and immediately following acute hemorrhage, with splenomegaly where there is both an expansion of plasma and sequestration of red cells( Kamija,2008).
Globally, anemia affects 1.62 billion people, which corresponds to 24.8% of the population (Table 1). The highest prevalence is in preschool-age children (47.4%), and the lowest prevalence is in men (12.7%). However, the population group with the greatest number of individuals affected is non-pregnant women (468.4 million) (Benoist et al.,2008).
Etiology and classification
Anemia has various causes and etiologies. Causes of anemia include a production defect, maturation defect, or survival defect. Sequestration and blood loss remove red blood cells from the circulation. Production defects may result from chronic disease, impaired renal function, hypometabolic status (hypothyroidism), and bone marrow damage. While maturation defects are either cytoplasmic where all defects are related to impaired hemoglobin synthesis (iron deficiency, thalassimias), or nuclear i.e.; DNA synthesis defects (folate, B12 deficiencies). Survival defects are intrinsic (inherited) as seen in metabolic enzymes deficiencies and hemoglobinopathies, while extrinsic (acquired) are like auto-immune hemolysis and malaria. Sequestration as in hyperspleenism, blood loss and GI hemorrhage (Hannaman,2005).
Another classification for anemia is based on RBC indices, mainly mean corpuscular volume (MCV). This classification includes the microcytic (MCVs 100 fL) anemias (table 2)(Drews,2003).
Reference intervals for red cell measurements vary with test methodology, environmental factors, sex, and age. Table (3) shows the normal references values of some parameters of complete blood count (CBC) (Tefferi et al.,2005).
Hemoglobin (Hb) concentration is the most reliable indicator of anemia at the population level. Measuring Hb concentration is relatively easy and inexpensive, and this measurement is frequently used as a proxy indicator of iron deficiency (Benoist et al.,2008).
According to hemoglobin percentage anemia may be mild, moderate, or severe in nature (table 4). Mild anemia, where hemoglobin ranges from 9.5-11 g/dl, is often asymptomatic and frequently escapes detection. Regarding moderate anemia, hemoglobin ranges from 8-9.5 g/dl, that may present with other symptoms and it needs timely management to prevent long-term complications. Finally, in severe anemia, the hemoglobin value is below 8 g/dl, which will need investigation and prompt management (Carley,2003).
Symptoms of anemia
Predominant symptoms of anemia are based on the severity of the disease rather than the specific etiology. Early symptoms include fatigue, tiredness, and poor exercise tolerance. As anemia worsens; the patient develops dyspnea on exertion and lightheadedness. Eventually confusion and altered mental status may develop (Fischer et al.,2006).
Most common signs found in examination of anemic population are, pallor of the conjunctiva, face, nail beds, and palmer creases. Further examination can reveal other sings related to underlying diseases, causing anemia as well (Karanth,2004).
There are several types and etiologies of anemia. Most common etiologies are nutritional anemia, hemolytic anemia, bone-marrow damage associated anemia and, anemia of chronic diseases (Munker et al.,2007).
In nutritional anemia, besides diseases which lead to losses of blood or impairment of the production of Hb, nutritional deficiencies play the most important role. Some vitamins like vitamin B12, folic acid and riboflavin influence the formation of Hb but the most important nutritional factor is iron deficiency (Kraemer & Zimmerman,2007).
Iron deficiency anemia (IDA), is the most common cause for microcytic anemia. IDA has variable causes being most common in females of productive age (pregnant or non-pregnant), and it may be caused by, blood loss as in reproductive system (menorrhagia), GI tract (esophagitis, esophageal varices, peptic ulcer, inflammatory bowel disease, hemorrhoids), and genitourinary system (hematuria). Malabsorption may cause IDA as seen in celiac disease, atrophic gastritis, or gastrectomy. While physiological IDA may be seen in growth spurts and pregnancy, also it may be secondary to dietary protocols as in vegans and elderly. Other causes of IDA may include hookworm infestation, and frequent venesection e.g. blood donation (Provan et al.,2004).
Iron deficiency anemia is a very well known concept but what is often not appreciated is the broad effect of iron deficiency on various tissues, organs and systems in the body in addition to iron deficiency anemia leading to concept of “Iron deficiency disease”. In this condition not only tissue delivery of oxygen is compromised but proliferation, growth, differentiation, myelinogenesis, immunofunction, energy metabolism, absorption and biotransformation are compromised leading to abnormal growth and behavior, mental retardation, reduced cardiac performance and work efficiency (Ghosh,2006).
Studies show that anemia due to iron deficiency tends to affect fast acting muscle function (sprint function) whereas cellular deficiency of iron tends to affect endurance exercise. Easy fatigability and decreased work performance in iron deficiency and its improvement following iron therapy has been reported in various case control studies. This finding has enormous consequences in national economy (Ghosh,2006).
A study was conducted where 41 iron-depleted, nonanemic women between the ages of 18 and 33 were assigned to receive 100 mg per day of ferrous sulfate, or placebo for six weeks. The amount of exercise increased with each subsequent week of the study. The women receiving the iron supplements took significantly less time to complete the 5-km trials, compared with women who did not receive iron. The work rate and oxygen consumption of the iron-supplemented group also improved, suggesting that their bodies worked more efficiently after taking iron (Ingels,2004).
Treatment of iron deficiency anemia
Simplest, safest and cheapest treatment for IDA is oral ferrous salts. Increasing dietary iron intake has no routine place in the management of iron deficiency except where intake is grossly deficient (Provan et al.,2004).
Iron absorption may be increased by taking it with 100 mg or more of vitamin C. Iron supplements should not be taken at the same time as coffee, tea, soy, or calcium supplements, since these substances interfere with iron absorption (Ingels,2004).
Effective iron replacement therapy should result in a rise of hemoglobin concentration of around 1 g/l per day (about 20 g/l every three weeks), but this varies from patient to patient. Once the hemoglobin concentration is within the normal range, iron replacement should continue for three months to replenish the iron stores (Provan,2003).
Nutritional anemia could be a result of other deficiencies. Most commonly vitamin B12, and folic acid causing macrocytic megalobalstic anemia (Kraemer & Zimmerman,2007).
Vitamin B12 deficiency, mostly due to pernicious anemia, which is an auto-immune disorder, results in decreased production of intrinsic factor. Other causes are malabsorption, and decreased dietary intake. And as for folic acid deficiency it is usually due to decreased dietary intake or less commonly, increased body demands (e.g., pregnancy) (Fischer et al.,2006).
Other rare deficiencies include vitamin A deficiency (produces chronic disorder like iron deficiency anemia), vitamin B6 deficiency (produce hypochromic microcytic anemia), vitamin C deficiency (associated with macrocytic anemia), vitamin E deficiency (seen in the neonatal period in low birth weight infants, that results in hemolytic anemia with abnormal RBC morphology), and starvation (normochromic anemia, which occurs in anorexia nervosa; features are not associated with any specific deficiency) (Provan et al.,2004).
The hemolytic anemias can be classified into acquired and inherited types. The acquired forms are usually caused by the development of autoantibodies against red cells( autoimmune hemolytic anemia, paroxysmal nocturnal hemoglobinuria, hemolytic disease of the newborn, parasitc infection ,and drug-induced hemolytic anemia), whereas the inherited forms are possibly due to red cell membrane defects(hereditary spherocytosis, hereditary elliptocytosis) red cell enzyme defects (deficiency of glucose-6-phosphate dehydrogenase, and pyruvate kinase), or abnormalities of the hemoglobin molecule (Sickle Cell Anemia, Thalassemias, HbC and, HbE). All hemolytic anemias have several common clinical features, as a result of both increased destruction and an increased compensatory production of red cells, most commonly anemia manifestations and spleenomegaly (Munker et al.,2007).
Bone-marrow damage associated anemias are hypoproliferative anemias which are normochromic, normocytic or macrocytic, and characterized by low reticulocyte count (Kasper et al.,2005).
Anemia of chronic disease is due defect in the ability to use the stored iron within the reticuloendothelial system. This anemia can virtually accompany any chronic inflammatory, infectious, or neoplastic condition. It can be either microcytic or normocytic (Fischer et al.,2006).