Iron-deficiency anemia

Iron deficiency is the most common cause of anemia and is usually due to blood loss. Iron deficiency anemia usually has a nonspecific symptomatology.

Erythrocytes have a tendency to microcytosis and hypochromia, iron stores are reduced, which is reflected in the low figures of serum ferritin and iron with high serum transferrin. When iron deficiency anemia is established, blood loss is assumed. Treatment is aimed at restoring iron reserves and treating blood loss.

Iron in the body is divided into active metabolism and storage pool. Total iron stores in the body are about 3.5 g in healthy men and 2.5 g in women; differences are related to body size, lower androgen levels and an inadequate iron reserve in women due to loss of iron with menstruation and pregnancy. Iron is distributed in humans as follows: hemoglobin - 2100 mg, myoglobin - 200 mg, tissue (heme and non-heme) enzymes - 150 mg, iron transport system - 3 mg. Stocks of the gland in the form of ferritin are found in cells and plasma (700 mg) and in cells in the form of hemosiderin (300 mg).

Absorption of iron occurs in the duodenum and upper parts of the jejunum. The absorption of iron is determined by the type of iron molecule and components of the ingested food. Absorption of iron occurs best when food contains iron in the form of heme (meat). Non-heme iron should reduce the status of iron and be released from food components by using a gastric secretion. Absorption of non-haem iron is reduced by other food components (for example, tea tannins, bran) and some antibiotics (for example, tetracycline). Ascorbic acid is the only component of ordinary food, which increases the absorption of non-heme iron.

The average diet contains 6 mg of elemental iron per 1 kcal of food, which provides adequate homeostasis for the gland. Of 15 mg of iron consumed with food, adults only absorb 1 mg, which roughly corresponds to the daily loss of iron with desquamation of skin cells and intestines. With iron deficiency, absorption increases, and although precise regulation mechanisms are unknown, absorption rises to 6 mg per day until its stock is restored. Children need iron more than adults, and absorption is higher to compensate for this need.

Iron from the cells of the intestinal mucosa is transferred to transferrin, an iron-transport protein synthesized by the liver. Transferrin can transport iron from cells (intestines, macrophages) to specific receptors of erythroblasts, placental cells and hepatic cells. For heme synthesis, transferrin transfers iron to mitochondria of erythroblasts, which include iron in protoporphyrin, resulting in the latter turning into heme. Transferrin (its half-life in blood plasma is 8 days) is then released for re-utilization. Synthesis of transferrin increases with iron deficiency, but decreases with all types of chronic diseases.

Iron, not used for erythropoiesis, is transferred by transferrin to the storage pool, which is represented by two forms. The most important is ferritin (a heterogeneous group of proteins surrounding the core of iron), which is a soluble and active fraction localized in the liver (in hepatocytes), bone marrow, spleen (in macrophages), erythrocytes and plasma. Iron, stored in ferritin, is ready for use for the needs of the body. The concentration of serum ferritin correlates with its stock (1 ng / ml = 8 mg of iron in the storage pool). The second pool of iron storage in the body is hemosiderin, which is relatively insoluble, and its stores are concentrated mainly in the liver (in Kupffer cells) and in the bone marrow (in macrophages).

Due to the limited absorption of iron, the body retains and re-uses it. Transferrin binds and re-uses available iron from old erythrocytes, which are subjected to phagocytosis by mononuclears. This mechanism provides about 97% of the daily requirement for iron (approximately 25 mg of iron). With age, the iron pool in the body tends to grow due to the fact that its elimination slows down.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]

Causes of iron deficiency anemia

Since iron is poorly absorbed, most people absorb it only in terms of daily requirements. Thus, even small losses, increased demand or reduced consumption of it leads to iron deficiency.

Blood loss is the most common cause of iron deficiency. In men, the source of bleeding is usually hidden and, as a rule, is located in the digestive tract. In premenopausal women, the most common cause of iron deficiency is loss of blood during menstruation (an average of 0.5 mg of iron per day). Another possible cause of blood loss in men and women is chronic intravascular hemolysis, if the amount of iron released during hemolysis exceeds the haptoglobin binding ability. Vitamin C deficiency can contribute to iron deficiency anemia through increased fragility of capillaries, hemolysis and bleeding.

Increasing the need for iron can also contribute to iron deficiency. From the age of two years to the adolescent period, rapid growth of the body requires a large expenditure of iron, and iron that comes with food is often not enough. In pregnancy, iron fetal consumption increases the need of the mother in it (on average 0.5 to 0.8 mg per day - see also "Anemia in Pregnancy"), despite the absence of menses. Lactation also increases the need for iron (an average of 0.4 mg per day).

Reduced iron absorption may be the result of gastrectomy and malabsorption syndrome in the upper parts of the small intestine. Rarely absorption decreases as a result of the use of non-food products (clay, starch, ice).

[14], [15], [16], [17], [18], [19], [20], [21]

Symptoms of iron deficiency anemia

The deficit develops in stages. At the first stage, iron consumption exceeds intake, causing a progressive shortage of iron stores in the bone marrow. With a decrease in the reserve, the absorption of iron with food is increased. Then, with the development of subsequent stages, the deficit is expressed so much that the synthesis of erythrocytes is disturbed. Eventually, anemia develops with its symptoms and signs.

Iron deficiency, if it is sufficiently pronounced and prolonged, may be the cause of dysfunction of iron-containing cellular enzymes. This dysfunction can contribute to the development of weakness and loss of vitality regardless of the anemia itself.

In addition to the usual manifestations of anemia with severe iron deficiency, there are some unusual symptoms. Patients may have a craving for eating inedible objects (for example, ice, earth, paint). Other symptoms of severe iron deficiency are glossitis, cheilosis, concave nails (coilonichia) and rarely dysphagia caused by the cricoid-esophageal membrane.

Diagnosis of iron deficiency anemia

Iron deficiency anemia is expected in patients with chronic blood loss or microcytic anemia, especially if there is a perverse appetite. In such patients it is necessary to perform a general blood test, to determine serum iron, jelly-binding capacity and serum ferritin.

Iron and iron binding ability (or transferrin) is usually determined together, as their relationship is important. There are various tests in which the spread of normal indicators depends on the methods of determination used. Normally, normal serum iron is 75 to 150 μg / dL (13-27 μmol / L) in men and 60 to 140 μg / dL (11-25 μmol / L) in women; total iron binding capacity is from 250 to 450 μg / dl (45-81 μmol / l). The concentration of serum iron decreases with iron deficiency and many chronic diseases and increases with hemolytic diseases and iron overload syndromes. Patients taking oral iron may have normal serum iron values, despite the existing iron deficiency, in such cases, the suspension of iron intake for 24-48 hours is required for evaluation. Iron binding capacity increases with iron deficiency.

The concentration of serum ferritin is closely related to total iron reserves. The normal spread in most laboratories ranges from 30 to 300 ng / ml and is on average 88 ng / ml in men and 49 ng / ml in women. Low concentrations (<12 ng / ml) are specific for iron deficiency. However, the level of ferritin can increase with liver damage (eg, hepatitis) and in some tumors (especially in acute leukemia, Hodgkin's lymphoma, GI tract).

The serum transferrin receptor reflects the number of erythrocyte progenitors that are capable of active proliferation, the indicator is sensitive and specific. The normal range is 3.0-8.5 μg / ml. The index rises in the early stages of iron deficiency and with increased erythropoiesis.

The most sensitive and specific criterion for iron deficiency erythropoiesis is the lack of iron in the bone marrow, although aspiration of the bone marrow is rarely performed for this purpose.

Iron deficiency anemia must be differentiated from other microcytic anemias.

If the conducted examinations exclude iron deficiency in a patient with microcytic anemia, the possibility of an anemia of a chronic disease, structural anomalies of hemoglobin and hereditary membranopathies of erythrocytes is considered. Clinical features, hemoglobin research (for example, hemoglobin and HbA2 electrophoresis) and genetic studies (eg, a-thalassemia) can help in the differentiation of these pathologies.

The results of laboratory tests help determine the stage of iron deficiency anemia. Stage 1 is characterized by a decrease in iron stores in the bone marrow; hemoglobin and serum iron remain normal, but the concentration of serum ferritin is reduced by less than 20 ng / ml. Compensatory enhancement of iron absorption is the cause of increased iron-binding capacity (transferrin level). At stage 2 there is a disturbance of erythropoiesis. Although the level of transferrin increases, serum iron concentration and transferrin saturation decrease. Violation of erythropoiesis occurs with a decrease in serum iron by less than 50 μg / dL (<9 μmol / L) and transferrin saturation by less than 16%. The concentration of serum ferritin receptors is increased (> 8.5 mg / l). At stage 3, anemia develops with normal erythrocyte indices and erythrocyte indices. At stage 4 hypochromia and microcytosis develop. At stage 5, iron deficiency is manifested by changes at the tissue level, which is manifested by the corresponding symptoms and complaints.

The diagnosis of "iron-deficiency anemia" involves the establishment of a source of bleeding. Patients with a clear source of blood loss (eg, women with menorrhagia) usually do not need further examinations. In men and women in the postmenopausal period, in the absence of obvious signs of bleeding, it is necessary to examine primarily the gastrointestinal tract, since anemia can be the only manifestation of a hidden malignant neoplasm of this localization. In rare cases, patients underestimate the significance of chronic nasal or urogenital bleeding, which should be taken into account in normal GI test results.

[22], [23], [24], [25], [26], [27], [28]

Treatment of iron deficiency anemia

Therapy with iron preparations without clarifying the cause of anemia is a bad practice; It is necessary to search for a source of blood loss even with mild anemia.

Iron preparations are used in the form of various salts of ferrous iron (ferrous sulfate, gluconate, fumarate) or trivalent saccharidic iron inside within 30 minutes before eating (food and antacids reduce iron absorption). A typical initial dose is 60 mg for elemental iron (eg, 325 mg of ferrous sulfate) 1-2 times per day. Higher doses are not absorbed, but can cause side effects, more often constipation. Ascorbic acid in the form of tablets (500 mg) or orange juice when taken with iron increases its absorption without side effects to the stomach. Parenteral iron has the same therapeutic efficacy as oral drugs, but it can have side effects such as anaphylactic shock, whey, thrombophlebitis, and pain. They are reserve drugs for patients who do not tolerate or do not take oral iron, or for patients who lose large amounts of blood in vascular diseases, in particular with violations from the capillaries (eg, congenital hemorrhagic telangiectasia). The dose of parenteral gland is determined by the hematologist. Iron therapy inside or parenterally needs to continue 6 or more months after the normalization of the hemoglobin level to replenish iron stores.

The effectiveness of treatment is estimated by a series of measurements of hemoglobin until normalization of erythrocyte indices is achieved. The rise of hemoglobin during the first 2 weeks is insignificant, then its growth occurs from 0.7 to 1 g per week before normalization. Anemia should be normalized within 2 months. An inadequate response to therapy presupposes continued bleeding, the presence of an infectious process or tumor, an insufficient intake of iron, or very rarely malabsorption when ingesting iron.