Iron Deficiency Anemia | HOW TO GET RID FROM ANEMIA | ANEMIA TREATMENT CAREFULLY

Iron Deficiency Anemia:

Iron deficiency is the most common cause of anemia and is usually due to blood loss; malabsorption is a much rarer cause. Symptoms are usually non-specific. There is a trend towards microcytosis and erythrocyte hypochromy, and iron reserves are reduced, as evidenced by the low level of serum ferritin and iron, as well as the high total iron-binding capacity of blood serum. This diagnosis should suspect hidden blood loss until proven otherwise. Treatment includes iron substitution therapy and blood loss treatment.

Pathophysiology

Iron contained in the body is distributed to the active metabolism and storage pool. The total amount of iron in the body is 3.5 g for healthy men and 2.5 g for women; the differences are related to body weight and the reduction of iron in women due to menstruation. Iron in the body is distributed over:

1. Hemoglobin 2 g (men), 1.5 g (women)
2. Ferritin 1 g (men), 0.6 g (women)
3. Hemosiderine 300 mg
4. Myoglobin 200 mg
5. Tissue enzymes (gem and non-gem), 150 mg
6. Compartement of transport iron, 3 mg

Iron absorption
Iron is absorbed in the duodenum and upper ileum. Iron absorption is determined by the type of iron molecule and the combination with other components of the food consumed. Iron absorption is maximum when the food contains gem iron (meat). Food-grade non-gem iron is usually trivalent and should be reduced to divalent and isolated from food components by gastric juice. Absorption of non-gem iron is reduced by certain food components (fibres and polyphenols in vegetables; tea tannins, including phosphoproteins; bran), certain antibiotics (e.g. tetracycline). Ascorbic acid is the only food component that increases the absorption of non-gem iron.

The average American diet contains 6 mg of elemental iron per 1,000 kcal of food and is adequate to maintain iron homeostasis. However, of the 15 mg of iron consumed with food per day, an adult adsorbs only 1 mg, which roughly corresponds to the daily loss of iron with desquamation of skin and intestinal epithelial cells. When iron reserves are depleted, absorption increases as a result of suppression of the activity of hepsidine, a key regulator of iron metabolism; however, absorption rarely increases to > 6 mg/day, except when additional iron sources are added (1). Children have a higher need for iron than adults, so absorption is also increased according to this need.

Iron transport and disposal
From intestinal mucosa cells, iron is transferred to transferrin, an iron transport protein that is synthesized in the liver; transferrin can transfer iron from cells (intestinal epithelial cells, macrophages) to specific receptors of erythroblasts, placental cells and hepatocytes. Transferrin transfers iron to the mitochondria of erythroblasts, where it is included in the protoporphyrins required for the synthesis of heme. Then transferrin (the half-life of plasma is 8 days) is released for subsequent reutilization. Synthesis of transferrin increases with iron deficiency, but decreases with any chronic diseases.

Iron accumulation and recirculation
Iron, which is not used for erythropoiesis, is transferred by transferrin, an iron transporting protein, to the storage pool; iron is stored in 2 forms: ferritin and hemociderin. The most important is ferritin (a heterogeneous group of proteins surrounding the iron core), which is a soluble and active replacement fraction accumulated in the liver (hepatocytes), bone marrow and spleen (macrophages), red blood cells and blood serum. Iron, accumulated in the form of ferritin, is ready to use for the needs of the body. The level of circulating (serum) ferritin corresponds to its reserves in the body (1 ng/ml in serum = 8 mg of iron in the reserve pools). The second source of iron accumulation is hemociderin, which is poorly soluble and is stored mainly in the liver (in Coopfer cells) and in the bone marrow (in macrophages).

Since iron absorption is limited, the body retains and recycles iron. Transferin binds and returns to iron recirculation, which is released when erythrocytes age during their phagocytosis by mononuclear phagocytes. This mechanism provides about 97% of the daily iron requirement (about 25 mg of iron). With age, iron accumulation tends to increase as iron elimination slows down.

Iron deficiency
Iron deficiency is developing in stages. At the first stage, the demand for iron exceeds its consumption, causing progressive depletion of iron reserves in the bone marrow. When iron reserves decrease, the absorption of iron with food increases in compensation. In late stages, iron deficiency has a negative impact on erythrocyte synthesis, which ultimately leads to the development of anaemia.

Severe and long-lasting iron deficiency can also cause dysfunction of iron cell enzymes.

Reference materials on pathophysiology
Nemeth E, Tuttle MS, Powelson J, et al: Hepcidin regulates iron outflow by binding to ferroportin and inducing its internalization. Science 306(5704):2090-2093, 2004.

Etiology
Because iron is poorly absorbed, the intake of iron with food hardly meets the daily needs of most people. But for those who follow Western diets, the likelihood that iron deficiency is only due to iron deficiency is extremely low. However, even moderate iron loss, combined with increased or reduced iron consumption, can cause iron deficiency.

Blood not gain is nearly regularly the cause of iron insufficiency. In men and women, the most common cause during the post-menopause period is chronic, occult bleeding, usually from the gastrointestinal tract (e.g. peptic ulcer, cancer, hemorrhoids). In women in pre-menopause, the common cause is the total blood loss during menstruation (on average 0.5 mg of iron/day). Intestinal bleeding due to ankylostomosis is a common cause in developing countries. Another less common cause is recurrent pulmonary bleeding (see Diffuse Alveolar Bleeding) and chronic intravascular hemolysis, where the amount of iron released during hemolysis exceeds the haptoglobin-binding capacity.

Increased demand for iron may contribute to the development of iron deficiency. When the body's rapid growth (children under 2 years of age and adolescents) requires large amounts of iron, its content in the diet is often insufficient. During pregnancy, the fetus' need for iron increases the mother's need for iron (on average, 0.5-0.8 mg/day-cm. Anemia during pregnancy), despite the absence of menstruation. Lactation also increases the need for iron (by an average of 0.4 mg/day).

Decreased iron absorption may be a consequence of gastrectomy or malabsorption syndromes such as celiac disease, atrophic gastritis and achlorhydria. Absorption is less frequently reduced when undernourished.

Clinical manifestations
Most of the symptoms of iron deficiency are related to anemia. These include fatigue, shortness of breath, weakness, dizziness and pallor.

In addition to the usual manifestations of anaemia in severe iron deficiency, there may be some rare symptoms. Patients may have pickacism, an abnormal craving for substances (e.g. ice, soil, paint). Other symptoms of severe deficiency include glossitis, halosis and concave nails (Coyloniasis).

Diagnosis
OAK, serum gland level, serum iron binding capacity, serum ferritin level, transferrin saturation, number of reticulocytes, erythrocyte volume distribution width (RDW), and peripheral blood smears

Bone marrow research is less common

Iron deficiency anemia should be suspected in patients with chronic bleeding loss or microcytic anemia, especially in patients with perverse appetite. In such patients, OAK, serum iron and ferritin levels, serum binding ability and reticulocyte count should be evaluated.

Determine iron levels and iron-binding capacity of blood serum (or transferrin), as the ratio of these indicators is important. Different methods of investigation exist; the range of normal values depends on the method used. In general, the normal serum iron level is 75-150 µg/dL (13-27 µmol/l) for men and 60-140 µg/dL (11-25 µmol/l) for women; the total serum binding capacity of the serum is 250-450 µg/dL (45-81 µmol/l). With iron deficiency and a number of chronic diseases the serum iron level is low, and with hemolytic disorders and iron overload syndromes it increases. Iron deficiency increases the ability of the serum to bind iron, while saturation of transferrin decreases.

Serum ferritin levels are closely related to the total iron content of the body. In most laboratories, the normal range is from 30 to 300 ng/ml, with an average of 88 ng/ml for men and 49 ng/ml for women. Low level (12 ng/ml) is a specific indicator of iron deficiency in the body. However, ferritin is an acute inflammatory protein and increases in inflammatory and infectious diseases (e.g. hepatitis) and neoplastic pathologies (especially acute leukemia, Hodgkin's lymphoma and gastrointestinal tumors). Under these conditions, serum ferritin levels of up to 100 ng/ml remain compatible with iron deficiency.

The number of reticulocytes in iron deficiency is low. As a rule, peripheral blood smears detect hypochromic erythrocytes with pronounced anisopoikylocytosis, which is reflected in the high volume distribution of erythrocytes (RDW).

The most sensitive and specific criterion for iron-deficient erythropoiesis is the lack of iron reserves in the bone marrow, but bone marrow research in such cases is rare.

Iron deficiency stages
The results of laboratory tests help to establish the stage of iron-deficiency anemia.

1. Stage 1 is characterized by a decrease in iron reserves in the bone marrow; hemoglobin and serum iron remain normal, but the serum ferritin content drops to < 20 ng/ml. A compensatory increase in iron absorption leads to an increase in the serum's iron-binding capacity (transferrin level).
2. Erythropoiesis is disturbed in the 2nd stage. Although transferrin levels increase, serum iron levels decrease; saturation of transferrin also decreases. Erythropoiesis is impaired if the serum iron content drops to < 50 mg/dL (< 9 µmol/l) and the transferrin saturation coefficient to < 16%. The number of serum transferrin receptors increases (> 8.5 mg/l).
3. Stage 3 develops anemia with normal erythrocyte indexes.
4. In stage 4, microcytic hypochromic anemia develops.
5. In stage 5, iron deficiency affects tissue metabolism, which leads to symptoms and signs of disease.

The presence of iron-deficiency anemia requires the establishment of its cause, which, as a rule, is bleeding. Patients with a clear cause of blood loss (women with menorrhagic diseases) may not have further examination. In men and women in the postmenopause without a clear cause of blood loss, it is necessary to examine the gastrointestinal tract, because anemia may be the only sign of a hidden tumor of the gastrointestinal tract. In rare cases, nasal or urogenital bleeding may be underestimated and should be analyzed in the presence of normal gastrointestinal examination results.

Other microcirculatory anemia
Iron-deficiency anemia should be distinguished from other microcytic anemia (Differential diagnosis of microcytic anemia caused by reduced erythrocyte production). If a patient with microcytic anemia has been excluded from iron deficiency by special methods of investigation, it is necessary to suspect the presence of chronic anemia and structural hemoglobin anomalies (e.g. hemoglobinopathy). Clinical signs, hemoglobin structure studies (electrophoresis, Hb A2 determination), genetic testing (e.g. alpha-thalassemia) can help to distinguish between these diseases.

Treatment
Oral iron medications
Less often iron medications for parenteral administration

The use of iron medication without determining the cause of the disease is a useless practice; the source of bleeding should be established even in the case of mild anemia.

Iron medications are prescribed in the form of salts of divalent iron (sulfate, gluconate, iron furmace) or iron trivalent sugar orally 30 minutes before meals (food or antacids can reduce iron absorption). Typically, the initial dose is 60 mg of elemental iron (e.g. 325 mg of iron sulphate) once a day (1). In higher doses, absorption does not increase, however, the risk of adverse events increases. Ascorbic acid in the form of tablets (500 mg) or orange juice increases iron absorption without causing gastrointestinal disorders.

Iron parenteral drugs have the same therapeutic efficacy as oral drugs, but they can cause various adverse effects: anaphylactoid reactions, serum disease, thrombophlebitis, pain syndrome. They are used in patients who cannot tolerate or take oral medications, as well as in patients who constantly lose large amounts of blood due to vascular diseases (such as hereditary hemorrhagic telangiectasia). The iron dose administered parenterally should be determined by a hematologist. Treatment with oral or parenteral iron medications should continue for ≥ 6 months after normalization of hemoglobin levels to replenish iron stores in tissues.

The response to treatment is assessed in a series of hemoglobin measurements prior to the normalization of red blood cells. During the first 2 weeks a slight increase in hemoglobin level is observed, then its rate increases to 0.7-1 g/week until the normalization of parameters. Anemia should be eliminated within 2 months. Incomplete response to treatment indicates prolonged bleeding, the presence of a major infectious or cancerous disease, insufficient iron intake with food or malabsorption of iron in the gastrointestinal tract.