Author: L.F. Matyukha
Anemia is one of the global problems of modern health care; according to recent data, 80% of all cases of anemia are associated with iron deficiency, which participates in the processes of oxygen transport, tissue respiration and has a great impact on the state of immunological resistance. The basis for the development of iron deficiency anemia (IDA) can be a variety of physiological and pathological processes that develop due to increased demand (childhood and adolescence, pregnancy), insufficient intake with food, impaired absorption or assimilation of iron. Since iron deficiency significantly complicates the course and prognosis of many diseases and conditions, timely and adequate correction of disorders caused by the deficiency of iron, an essential element for normal metabolism, is required. Given its widespread prevalence in various age groups, iron deficiency appears to be one of the serious challenges faced by practicing physicians regardless of specialization.
This pathology was one of the topics discussed at the scientific and practical conference “Topical issues of diagnosis, treatment, rational pharmacotherapy, dispensary and rehabilitation in the practice of a family doctor”, which was held at the I. Y. Gorbachevsky Ternopil State Medical University. The focus of attention of the large audience was a wide range of aspects of practical healthcare, including issues of hematology.
The current state of the problem of iron deficiency in different age groups in the report “Iron deficiency anemia” was presented by the president of the Ukrainian Association of Family Medicine, chief supernumerary specialist of the Ministry of Health of Ukraine in the specialty “General practice – family medicine”, head of the Department of Family Medicine and outpatient care of the National Medical Academy of Postgraduate Education named after P. L. Shupyk (P. L. Shupyk). P.L. Shupyk National Medical Academy of Postgraduate Education (Kiev), Doctor of Medical Sciences, Professor Larisa Fedorovna Matyukha.
– WDD is a polyoetiologic disease that develops as a result of a decrease in the total amount of iron in the body, which leads to impaired formation and reduction of hemoglobin (Hb), erythrocytes, development of trophic disorders in tissues and organs.
According to 2014 data from the World Health Organization (WHO), more than 1.2 billion people in the world suffer from iron deficiency. Among pregnant women, the incidence of iron deficiency is 20-80%; in Central and Eastern Europe, 20-22% of women and 3-9% of men have overt signs of iron deficiency. Since in the structure of all anemias ZHDA occupies 88.68%, this pathology is more often encountered by a family physician rather than a hematologist.
In Ukraine, iron deficiency is most common among preschool children (22.2% of cases). Iron deficiency is detected in 9.2% of women of reproductive age, and among pregnant women this figure rises to 27.3%, while iron deficiency is a risk factor and predictor of pregnancy and childbirth pathology: prematurity, congenital malformations, perinatal and maternal mortality.
In general, iron constitutes only 0.00065% of human body weight; a man weighing 70 kg contains approximately 4.5 g (50 mg/kg) of this trace element. The iron content of a 60 kg woman is approximately 4 g (35 mg/kg). The sources of this micronutrient are iron from food and absorbed in the intestine, and iron from red blood cells that are broken down during the process of red blood cell renewal. The process of iron absorption in the intestine is determined by the amount of this trace element, the form of its cation (Fe2+, Fe3+) and the state of the intestinal mucosa. Any disorders of the latter (malabsorption syndrome, irritable bowel syndrome, etc.) lead to impaired iron absorption and the development of iron deficiency in the body.
Iron absorption occurs mainly in the duodenum and at the beginning of the small intestine, intensified under the influence of gastric juice, ascorbic acid, as well as proteins of animal origin. At the same time ascorbic acid forms complexes with iron, which are well soluble in the acidic environment of the stomach, and continues to maintain their solubility even in the alkaline environment of the small intestine.
The mechanism of iron absorption consists in its transfer into the enterocyte with the help of DMT-1 protein (divalent metal transporter). At the same time, only the water-soluble divalent form of iron (Fe2+) can be transported directly into the cell, while the trivalent iron (Fe3+), which is poorly soluble in the alkaline environment of the intestine, must be reduced to Fe2+ before absorption, which has a higher bioavailability than Fe3+.
Almost all iron in the human body is part of various proteins and enzymes and is found in several forms. Cellular iron makes up a significant part of the total amount and is part of heme-containing compounds: hemoglobin (75%), myoglobin (3.5%) enzymes (0.5%). Extracellular iron includes free plasma iron and iron-binding serum proteins (transferrin, lactoferrin) involved in iron transport. Depot iron is represented by ferritin and hemosiderin, protein compounds that are predominantly deposited in the liver, spleen, kidney, and muscle; these compounds are incorporated into metabolism in cellular iron deficiency.
Vitamins and trace elements, each of which plays an important biological role, are also required for iron absorption in the intestine and red blood cell synthesis in the bone marrow. For example, folic acid is involved in the synthesis of erythrocyte DNA, ascorbic acid potentiates the effect of folic acid and stimulates iron absorption; vitamin B12 is necessary for the formation of lipid stroma of erythrocytes, and nicotinic acid strengthens this lipid membrane, protecting against hemolysis; vitamin B6 is involved in the synthesis of heme; zinc is part of the enzyme of erythrocyte carboanhydrase. It has been found that the deficiency of B vitamins increases the decrease in the level of enzymatic activity and accumulation of lipid peroxidation products in iron deficiency.
The cause of iron deficiency (sideropenia) in the body and the development of DALD is the imbalance in the direction of predominance of consumption of this trace element over the intake, which is observed in various physiological and pathological conditions. The most common causes of iron deficiency are:
- alimentary iron deficiency (diets, vegetarianism, malnutrition);
- increased need for iron (pregnancy, lactation, prematurity, rapid growth of the child, e.g. in adolescence, intensive sports);
- chronic blood loss (frequent nosebleeds, anal fissure, tumors, gastrointestinal polyps, hypermenorrhea, metrorrhagia);
- absorption disorders (malabsorption, achlorhydria, gastrectomy, inflammatory bowel disease);
- iron transport disorders (atransferrinemia);
- worm infestations in children.
The main elements of the pathogenesis of disorders in sideropenia consist in the slowing of heme synthesis and inhibition of hemoglobin formation, which leads to the development of anemia with dystrophic changes in tissues and organs. In addition, impaired synthesis of heme-containing compounds (myoglobin, enzymes) leads to decreased activity of antioxidant factors with intensification of lipid peroxidation. Thus, the development of iron deficiency is directly related to the physiological role of iron in the body and its participation in the processes of tissue respiration due to its ability to oxidation and reduction.
Pathogenetically, the development of iron deficiency state is usually divided into three stages:
- prelatent (deposition insufficiency) – reduction of iron stores; serum ferritin and iron content in the bone marrow decreases, iron absorption increases;
- latent (iron-deficient erythropoiesis, most common in the population) – serum iron content is slightly reduced, but Hb level is above the lower limit of normal, transferrin concentration is increased; tissue cytochrome oxidase and sideroblasts in the bone marrow are reduced; total iron-binding activity of serum and iron absorption in the intestine are increased;
- manifest – accompanied by hypochromic anemia with decreased hemoglobin, erythrocytes and serum iron.
Clinical manifestations of iron deficiency in the pre-latent stage are nonspecific or not determined. Latent iron deficiency is characterized by manifestations of sideropenia syndrome in the form of dystrophy of the skin and its appendages; perversion of taste and smell; muscle hypotonia (urinary incontinence) and muscle pain; weakness, malaise, memory and attention loss. A number of symptoms and syndromes characteristic of sideropenia are observed in manifest LDD; it has been established that tissue hypoxia, decreased enzymatic activity and accumulation of underoxidized metabolic products lead to the development of atrophic changes in the skin and its appendages, mucous membranes of the digestive and respiratory tracts, genital organs, sclera dystrophy (blue sclera syndrome).
At WDD against the background of cellular hypoxia and dystrophic changes in organs immunological resistance of the organism decreases, which is accompanied by aggravation of chronic inflammatory processes of various localization.
Hemic hypoxia contributes to the development of interventricular septal hypertrophy, and in old age can provoke exacerbation of ischemic heart disease with subsequent development of left ventricular insufficiency. In hypoxia, a complex of adaptive mechanisms is formed: dyspnea, tachycardia, blood pressure fluctuations, functional murmurs over the heart and large vessels.
Iron is an essential trace element for the formation of dopamine D2-receptors in CNS cells; their deficiency disrupts the development and normal functioning of dopaminergic neurons, which is manifested by changes in the psycho-emotional state of a person, apathy, memory and attention disorders, decreased tolerance to physical activity.
Thus, the consequence of iron deficiency in the body is not only hematologic symptomatology, but also impaired function of all cells, especially in highly aerobic tissues.
WHO defines the following diagnostic criteria for anemia: decreased Hb levels ≤130 g/L in men, ≤120 g/L in women and ≤110 g/L in pregnant women; hypochromia (color index ≤0.86); erythrocyte microcytosis and anisocytosis (MCV (mean erythrocyte volume) ≤75 fL, MCH (mean hemoglobin content in erythrocyte) ≤24 pg); decreased serum ferritin and iron (≤12 µg/L and 11.6 µmol/L, respectively). In clinical practice, the following assessment of anemia severity is also accepted: mild (Hb 110-90 g/L, Er 3.0-3.5×1012/L), moderate (Hb 90-70 g/L, Er 2.5-3.0×1012/L), severe (Hb ≤70 g/L, Er 1.0-2.0×1012/L), extremely severe (Hb ≤55 g/L, Er ≤1.0×1012/L). One should pay attention to the fact that clinical symptomatology of WDD is manifested, as a rule, at a moderate degree of severity, and at a mild course only laboratory parameters serve as objective criteria. At the same time, determination of serum ferritin concentration is considered to be the most evidence-based test for diagnosing iron deficiency (level of evidence A).
Modern therapy of iron deficiency includes non-medication (balanced nutritious diet) and medication correction of sideropenia. Rational drug therapy of ALD is determined by the following rules: identification and correction of the causes of sideropenia; correct calculation of iron dose; observance of the stage and duration of treatment (until recovery of the relevant peripheral blood parameters and iron depot in the body). The first stage (normalization of Hb and Er levels) lasts 3-4 weeks, the second stage (saturation therapy) lasts ≥3-6 months. Treatment monitoring provides control of blood parameters every 10-14 days, during partial remission – once a month, during complete remission – once every 6 months.
WHO recommendations for the prescription of iron preparations stipulate the priority of oral forms containing Fe2+, with the daily dose in adults should reach 2 mg/kg of elemental iron; the total duration of treatment – at least 3 months. It is established that oral preparations in the form of iron sulfates have good solubility and high bioavailability. In addition, to potentiate therapeutic and preventive effects, modern iron preparations contain ascorbic acid (prevents iron oxidation) and B vitamins (stimulate erythropoiesis and Hb synthesis).
The balanced antianemic complex Fersinol Z (World Medicine, Great Britain) is successfully used in daily clinical practice. Each capsule contains iron and zinc sulfate, as well as vital B vitamins, ascorbic acid, nicotinamide. Modern technologies of production of Fersinol Z allow to achieve a separate and gradual release and absorption of all components of the drug, which demonstrate a complementary action in the body. Due to its balanced composition, Fersinol Z has high bioavailability and exhibits pronounced antihypoxant and antioxidant activity. Fersinol Z is recommended for use in the case of WDA, latent sideropenia, iatrogenic anemia (surgery, hemodialysis, etc.), hypo- and avitaminosis. Convenient mode of administration (1-2 capsules per day) and good tolerability provide high adherence in patients of different age groups receiving Fersinol Z, which is an important factor in the success of treatment and prevention of WDA.
In cases where intestinal iron absorption is impaired, preparations for parenteral administration are used. World Medicine Company offers a complex solution to the problems of ZhDA: Fersinol ampoules 2 mg/mL No. 5 + Fersinol Z capsules No. 30.
Prepared by Natalia Pozdnyakova
Published in the medical newspaper “Health of Ukraine of the 21st century” № 18 (391)’2016