Iron deficiency anemia

Iron deficiency is the most common cause of anemia and is usually due to blood loss. Iron deficiency anemia usually has non-specific symptoms.

Red blood cells tend to be microcytic and hypochromic, and iron stores are reduced, as reflected by low serum ferritin and iron levels with high serum transferrin levels. When iron deficiency anemia is diagnosed, blood loss is assumed. Treatment is aimed at restoring iron stores and treating blood loss.

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

Iron absorption occurs in the duodenum and upper jejunum. Iron absorption is determined by the type of iron molecule and the components of the ingested food. Iron absorption is best when the food contains iron in the form of heme (meat). Non-heme iron must reduce the iron status and be released from food components via gastric secretions. Non-heme iron absorption is reduced by other food components (e.g., tea tannins, bran) and some antibiotics (e.g., tetracycline). Ascorbic acid is the only component of normal food that increases non-heme iron absorption.

The average diet contains 6 mg of elemental iron per kcal of food, which ensures adequate iron homeostasis. Of the 15 mg of iron consumed in the diet, only 1 mg is absorbed in adults, which roughly corresponds to the daily loss of iron from desquamation of skin and intestinal cells. In iron deficiency, absorption increases, and although the precise mechanisms are unknown, absorption increases to 6 mg per day until stores are restored. Children have higher iron requirements than adults, and absorption is higher to compensate for this requirement.

Iron from the intestinal mucosa cells is transferred to transferrin, an iron transport protein synthesized by the liver. Transferrin can transport iron from cells (intestines, macrophages) to specific receptors on erythroblasts, placental cells, and liver cells. To synthesize heme, transferrin transports iron to the erythroblast mitochondria, which incorporate the iron into protoporphyrin, which converts the latter into heme. Transferrin (its half-life in blood plasma is 8 days) is then released for reutilization. Transferrin synthesis increases with iron deficiency but decreases in all types of chronic diseases.

Iron not used for erythropoiesis is transported by transferrin to a storage pool, which exists in two forms. The most important is ferritin (a heterogeneous group of proteins surrounding a 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 readily available for use by the body. The serum ferritin concentration is related to its storage (1 ng/mL = 8 mg of iron in the storage pool). The second iron storage pool in the body is hemosiderin, which is relatively insoluble and is concentrated mainly in the liver (in Kupffer cells) and bone marrow (in macrophages).

Because iron absorption is limited, the body conserves and reutilizes it. Transferrin binds and reutilizes available iron from old red blood cells that are phagocytosed by mononuclear cells. This mechanism provides about 97% of the daily iron requirement (approximately 25 mg of iron). With age, the iron pool in the body tends to increase because its elimination slows down.

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Causes of Iron Deficiency Anemia

Because iron is poorly absorbed, most people only absorb enough iron to meet their daily needs. Thus, even small losses, increased needs, or decreased intakes result in iron deficiency.

Blood loss is the most common cause of iron deficiency. In men, the source of bleeding is usually hidden and is usually located in the gastrointestinal tract. In premenopausal women, the most common cause of iron deficiency is menstrual blood loss (an average of 0.5 mg iron per day). Another possible cause of blood loss in both men and women is chronic intravascular hemolysis if the amount of iron released during hemolysis exceeds the haptoglobin-binding capacity. Vitamin C deficiency may contribute to iron deficiency anemia through increased capillary fragility, hemolysis, and bleeding.

Increased iron requirements may also contribute to iron deficiency. From the age of two until adolescence, rapid growth of the body requires a large amount of iron, and iron supplied with food is often insufficient. During pregnancy, the fetus's iron intake increases the mother's iron requirement (on average, 0.5 to 0.8 mg per day - see also "Anemia during pregnancy"), despite the absence of menstruation. Lactation also increases the need for iron (on average, 0.4 mg per day).

Decreased iron absorption may result from gastrectomy and malabsorption syndrome in the upper small intestine. Rarely, absorption is reduced by ingestion of non-food products (clay, starch, ice).

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Symptoms of Iron Deficiency Anemia

The deficiency develops in stages. At the first stage, iron consumption exceeds intake, causing a progressive deficiency of iron reserves in the bone marrow. As the reserve decreases, iron absorption with food increases in compensation. Then, as subsequent stages develop, the deficiency is so pronounced that red blood cell synthesis is disrupted. Ultimately, anemia develops with its symptoms and signs.

Iron deficiency, if severe and prolonged, can cause dysfunction of iron-containing cellular enzymes. This dysfunction can contribute to weakness and loss of vitality independent of the anemia itself.

In addition to the usual manifestations of anemia, severe iron deficiency may cause some unusual symptoms. Patients may have a craving for inedible objects (e.g., ice, dirt, paint). Other symptoms of severe iron deficiency include glossitis, cheilosis, concave nails (koilonychia), and, rarely, dysphagia due to cricoesophageal membrane.

Diagnosis of iron deficiency anemia

Iron deficiency anemia is suspected in patients with chronic blood loss or microcytic anemia, especially if there is a perverted appetite. In such patients, a complete blood count should be performed, serum iron, iron-binding capacity, and serum ferritin should be determined.

Iron and iron-binding capacity (or transferrin) are usually measured together because their relationship is important. There are various tests, with the normal range depending on the assay used. Typically, normal serum iron is 75 to 150 mcg/dL (13 to 27 μmol/L) in men and 60 to 140 mcg/dL (11 to 25 μmol/L) in women; total iron-binding capacity is 250 to 450 mcg/dL (45 to 81 μmol/L). Serum iron concentrations are low in iron deficiency and many chronic diseases and high in hemolytic diseases and iron overload syndromes. Patients taking oral iron may have normal serum iron values despite iron deficiency, in which case iron intake should be withheld for 24 to 48 hours for evaluation. Iron-binding capacity increases with iron deficiency.

Serum ferritin concentration is closely related to total iron stores. The normal range in most laboratories is 30 to 300 ng/mL, with an average of 88 ng/mL in men and 49 ng/mL in women. Low concentrations (< 12 ng/mL) are specific for iron deficiency. However, ferritin levels may increase with liver damage (eg, hepatitis) and some tumors (especially acute leukemia, Hodgkin's lymphoma, and gastrointestinal tumors).

The serum transferrin receptor reflects the amount of erythrocyte precursors capable of active proliferation; the indicator is sensitive and specific. The normal range is 3.0-8.5 μg/ml. The indicator increases in the early stages of iron deficiency and with increased erythropoiesis.

The most sensitive and specific criterion for iron-deficient erythropoiesis is the absence of iron stores in the bone marrow, although bone marrow aspiration is rarely performed for this purpose.

Iron deficiency anemia must be differentiated from other microcytic anemias.

If the tests performed exclude iron deficiency in a patient with microcytic anemia, the possibility of anemia of chronic disease, structural hemoglobin abnormalities, and hereditary red blood cell membranopathy is considered. Clinical features, hemoglobin testing (e.g., hemoglobin electrophoresis and HbA2), and genetic testing (e.g., a-thalassemia) can help differentiate these pathologies.

Laboratory tests help determine the stage of iron deficiency anemia. Stage 1 is characterized by decreased bone marrow iron stores; hemoglobin and serum iron remain normal, but serum ferritin concentration decreases by less than 20 ng/mL. Compensatory increase in iron absorption causes an increase in iron-binding capacity (transferrin level). Stage 2 is characterized by impaired erythropoiesis. Although transferrin level increases, serum iron concentration and transferrin saturation decrease. Erythropoiesis is impaired when serum iron decreases by less than 50 μg/dL (< 9 μmol/L) and transferrin saturation by less than 16%. Serum ferritin receptor concentration increases (> 8.5 mg/L). Stage 3 is characterized by anemia with normal red blood cell counts and red blood cell indices. Stage 4 is characterized by hypochromia and microcytosis. At stage 5, iron deficiency manifests itself through changes at the tissue level, which is manifested by corresponding symptoms and complaints.

The diagnosis of iron deficiency anemia requires the establishment of a source of bleeding. Patients with an obvious source of blood loss (e.g., women with menorrhagia) usually do not require further examination. In men and postmenopausal women, in the absence of obvious signs of bleeding, it is necessary to examine the gastrointestinal tract first, since anemia may be the only manifestation of a hidden malignant neoplasm in this localization. In rare cases, patients underestimate the significance of chronic nasal or urogenital bleeding, which should be taken into account if the results of the gastrointestinal examination are normal.

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Treatment of iron deficiency anemia

Iron therapy without determining the cause of anemia is poor practice; a search for the source of blood loss is necessary even in mild anemia.

Iron preparations are used in the form of various salts of divalent iron (ferrous sulfate, gluconate, fumarate) or trivalent iron saccharide orally 30 minutes before meals (food and antacids reduce iron absorption). A typical starting dose is 60 mg of elemental iron (e.g., 325 mg of ferrous sulfate) 1-2 times a day. Higher doses are not absorbed, but may cause side effects, most often constipation. Ascorbic acid in the form of tablets (500 mg) or orange juice when taken with iron increases its absorption without side effects for the stomach. Parenteral iron has the same therapeutic efficacy as oral preparations, but may have side effects such as anaphylactic shock, serum sickness, thrombophlebitis, pain. They are reserve drugs for patients who cannot tolerate or do not take oral iron, or for patients who lose large amounts of blood due to vascular disease, particularly capillary disorders (eg, congenital hemorrhagic telangiectasia). The dose of parenteral iron is determined by a hematologist. Oral or parenteral iron therapy should be continued for 6 months or more after hemoglobin levels have returned to normal to replenish iron stores.

The effectiveness of treatment is assessed by a series of hemoglobin measurements until normalization of red blood cell counts is achieved. The increase in hemoglobin during the first 2 weeks is insignificant, then its growth occurs from 0.7 to 1 g per week until normalization. Anemia should be normalized within 2 months. Insufficient response to therapy suggests continued bleeding, the presence of an infectious process or tumor, insufficient iron intake, or very rarely malabsorption when taking iron orally.