Diagnosis of Iron Deficiency Anemia
The main guidelines in the laboratory diagnosis of iron deficiency anemia are as follows:
- The average content of hemoglobin in the red blood cell in picograms (normal 27-35 pg) is reduced. To calculate it, the color index is multiplied by 33.3. For example, with a color index of 0.7 x 33.3, the hemoglobin content is 23.3 pg.
- The average concentration of hemoglobin in the red blood cell is reduced; normally it is 31-36 g / dl.
- Hypochromia of red blood cells is determined by microscopy of a smear of peripheral blood and is characterized by an increase in the zone of central enlightenment in the red blood cell; normal ratio of central enlightenment to peripheral dimming is 1: 1; with iron deficiency anemia – 2 + 3: 1.
- Microcytosis of red blood cells – a decrease in their size.
- The color of erythrocytes, different in intensity, is anisochromia; the presence of both hypo- and normochromic red blood cells.
- A different form of red blood cells is poikilocytosis.
- The number of reticulocytes (in the absence of blood loss and a period of ferrotherapy) with iron deficiency anemia remains normal.
- The white blood cell count is also within normal limits (with the exception of cases of blood loss or cancer).
- The platelet count often remains within normal limits; moderate thrombocytosis is possible with blood loss at the time of examination, and platelet count decreases when iron deficiency anemia is based on blood loss due to thrombocytopenia (for example, with DIC, Verlhof disease).
- Reducing the number of siderocytes until their disappearance (siderocyte is a red blood cell containing iron granules). In order to standardize the manufacture of peripheral blood smears, it is recommended to use special automatic devices; the monolayer of cells formed in this way improves the quality of their identification.
- Decrease in the content of iron in blood serum (normally in men 13-30 micromol / l, in women 12-25 micromol / l).
- OZHSS is increased (reflects the amount of iron which can be connected due to free transferrin; OZHSS normally – 30-86 micromol / l).
- Study of transferrin receptors by enzyme immunoassay; their level is elevated in patients with iron deficiency anemia (in patients with anemia of chronic diseases – normal or reduced, despite the similar indicators of iron metabolism.
- The latent iron-binding ability of blood serum is increased (determined by subtracting the content of serum iron from the OGSS indicators).
- The percentage of transferrin saturation with iron (the ratio of serum iron to OZHSS; normal 16-50%) is reduced.
- The level of serum ferritin is also reduced (normally 15-150 mcg / l).
At the same time, in patients with iron deficiency anemia, the number of transferrin receptors was increased and the level of erythropoietin in the blood serum was increased (compensatory hematopoietic reactions). The volume of erythropoietin secretion is inversely proportional to the oxygen transport capacity of the blood and directly proportional to the oxygen demand of the blood. Keep in mind that serum iron levels are higher in the morning; before and during menstruation, it is higher than after menstruation. The iron content in the blood serum in the first weeks of pregnancy is higher than in its last trimester. The level of serum iron rises on the 2-4th day after treatment with iron-containing drugs, and then decreases. A significant consumption of meat products on the eve of the study is accompanied by hypersidemia. These data must be taken into account when evaluating the results of a study of serum iron. It is equally important to observe the technique of laboratory research, the rules of blood sampling. So, the tubes in which the blood is collected must first be washed with hydrochloric acid and bidistilled water.
A myelogram study reveals a moderate normoblastic reaction and a sharp decrease in the content of sideroblasts (erythrokaryocytes containing iron granules).
Iron reserves in the body are judged by the results of a desferal test. In a healthy person, after intravenous administration, 500 mg of desferal is excreted in the urine from 0.8 to 1.2 mg of iron, while in a patient with iron deficiency anemia, iron excretion is reduced to 0.2 mg. The new domestic drug is identical to defericolixes with Desferal, but it circulates in the blood longer and therefore more accurately reflects the level of iron stores in the body.
Given the level of hemoglobin, iron deficiency anemia, like other forms of anemia, is divided into severe, moderate and mild anemia. With mild iron deficiency anemia, the hemoglobin concentration is below normal, but more than 90 g / l; with moderate-grade iron deficiency anemia, the hemoglobin content is less than 90 g / l, but more than 70 g / l; with severe iron deficiency anemia, the hemoglobin concentration is less than 70 g / l. However, the clinical signs of severity of anemia (hypoxic symptoms) do not always correspond to the severity of anemia according to laboratory criteria. Therefore, a classification of anemia according to the severity of clinical symptoms is proposed.
According to clinical manifestations, 5 degrees of severity of anemia are distinguished:
- anemia without clinical manifestations;
- moderate anemic syndrome;
- severe anemic syndrome;
- anemic precoma;
- anemic coma.
A moderate severity of anemia is characterized by general weakness, specific symptoms (for example, sideropenic or signs of vitamin B12 deficiency); with a pronounced severity of anemia, palpitations, shortness of breath, dizziness, etc. appear. Precomatous and coma can develop in a matter of hours, which is especially typical for megaloblastic anemia.
Modern clinical studies show that laboratory and clinical heterogeneity is observed among patients with iron deficiency anemia. So, in some patients with signs of iron deficiency anemia and associated inflammatory and infectious diseases, the level of serum and erythrocyte ferritin does not decrease, however, after the elimination of the exacerbation of the underlying disease, their content decreases, which indicates the activation of macrophages in the processes of iron expenditure. In some patients, the level of erythrocyte ferritin even rises, especially in patients with a prolonged course of iron deficiency anemia, which leads to ineffective erythropoiesis. Sometimes there is an increase in the level of serum iron and erythrocyte ferritin, a decrease in serum transferrin. It is assumed that in these cases, the process of transfer of iron to gemsynthesizing cells is disrupted. In some cases, a deficiency of iron, vitamin B12 and folic acid is determined simultaneously.
Thus, even the level of serum iron does not always reflect the degree of iron deficiency in the body in the presence of other signs of iron deficiency anemia. Only the level of OZHSS at an iron deficiency anemia is always increased. Therefore, not a single biochemical indicator, including OZHSS cannot be considered as an absolute diagnostic criterion for iron deficiency anemia. At the same time, the morphological characteristics of peripheral blood red blood cells and a computer analysis of the main parameters of red blood cells are decisive in the screening diagnosis of iron deficiency anemia.
Diagnosis of iron deficiency conditions is difficult in cases where the hemoglobin content remains normal. Iron deficiency anemia develops in the presence of the same risk factors as iron deficiency anemia, as well as in individuals with an increased physiological need for iron, especially in premature babies at an early age, in adolescents with a rapid increase in growth and body weight, in blood donors, with alimentary dystrophy. At the first stage of iron deficiency, clinical manifestations are absent, and iron deficiency is determined by the content of hemosiderin in bone marrow macrophages and by the absorption of radioactive iron in the digestive tract. At the second stage (latent iron deficiency), an increase in the concentration of protoporphyrin in erythrocytes is observed, the number of sideroblasts decreases, morphological signs (microcytosis, erythrocyte hypochromia) appear, the average hemoglobin content and concentration in erythrocytes decrease, the level of serum and erythrocyte ferritin decreases, and transferrin is saturated with iron. The hemoglobin level in this stage remains quite high, and clinical signs are characterized by a decrease in exercise tolerance. The third stage is manifested by clear clinical and laboratory signs of anemia.
Examination of patients with iron deficiency anemia
To exclude anemia, which has common features with iron deficiency anemia, and to identify the causes of iron deficiency, a complete clinical examination of the patient is necessary:
General blood test with the obligatory determination of the number of platelets, reticulocytes, the study of the morphology of red blood cells.
Biochemical blood test: determination of the level of iron, OZHSS, ferritin, bilirubin (bound and free), hemoglobin.
In all cases, it is necessary to examine bone marrow punctate before the appointment of vitamin B12 (primarily for differential diagnosis with megaloblastic anemia).
To identify the cause of iron deficiency anemia in women, a preliminary consultation with a gynecologist is required to exclude diseases of the uterus and its appendages, and in men, a proctologist is required to exclude bleeding hemorrhoids and a urologist to exclude prostate pathology.
Cases of extragenital endometriosis, for example in the respiratory tract, are known. In these cases hemoptysis is observed; fibrobronchoscopy with a histological examination of the biopsy of the bronchial mucosa allows you to establish a diagnosis.
The examination plan also includes X-ray and endoscopic examination of the stomach and intestines in order to exclude ulcers, tumors, including glomic, as well as polyps, diverticulum, Crohn’s disease, ulcerative colitis, etc. If pulmonary siderosis is suspected, radiography and tomography of the lungs are carried out, sputum examination for alveolar macrophages containing hemosiderin; in rare cases, a histological examination of a lung biopsy is necessary. If kidney pathology is suspected, a general urine test, a blood serum test for urea and creatinine are required, and, according to indications, an ultrasound and x-ray examination of the kidneys. In some cases, it is necessary to exclude endocrine pathology: myxedema, in which iron deficiency can develop secondarily due to damage to the small intestine; polymyalgia rheumatica is a rare disease of connective tissue in older women (less often in men), characterized by pain in the muscles of the shoulder or pelvic girdle without any objective changes in them, and in the analysis of blood – anemia and an increase in ESR.
Differential diagnosis of iron deficiency anemia
When making a diagnosis of iron deficiency anemia, a differential diagnosis with other hypochromic anemias is necessary.
Iron redistribution anemia is a fairly common pathology and in terms of frequency of development takes the second place among all anemia (after iron deficiency anemia). It develops in acute and chronic infectious and inflammatory diseases, sepsis, tuberculosis, rheumatoid arthritis, liver diseases, oncological diseases, ischemic heart disease, etc. The mechanism of development of hypochromic anemia in these conditions is associated with redistribution of iron in the body (it is mainly in the depot) and impaired the mechanism of iron recycling from the depot. With the above diseases, the macrophage system is activated when macrophages under the conditions of activation firmly retain iron, thereby disrupting the process of its recycling. A general blood test showed a moderate decrease in hemoglobin (<80 g / l).
The main differences from iron deficiency anemia are:
- increased serum ferritin, which indicates an increased iron content in the depot;
- the level of serum iron may remain within normal values or be moderately reduced;
- OZHSS remains within the normal range or decreases, which indicates the absence of serum Fe-starvation.
Iron-saturated anemia develops as a result of a violation of heme synthesis, which is due to heredity or may be acquired. Hem is formed from protoporphyrin and iron in red blood cells. With iron-saturated anemia, there is a violation of the activity of enzymes involved in the synthesis of protoporphyrin. The consequence of this is a violation of heme synthesis. Iron, which was not used for heme synthesis, is deposited in the form of ferritin in bone marrow macrophages, as well as in the form of hemosiderin in the skin, liver, pancreas, myocardium, as a result of which secondary hemosiderosis develops. In a general blood test, anemia, erythropenia, and a decrease in color index will be recorded.
The indicators of iron metabolism in the body are characterized by an increase in the concentration of ferritin and serum iron level, normal OZHSS indicators, an increase in the transferrin saturation with iron (in some cases reaches 100%). Thus, the main biochemical indicators that make it possible to assess the state of iron metabolism in the body are ferritin, serum iron, OZHSS, and% transferrin saturation with iron.
The use of indicators of iron metabolism in the body enables the clinician:
- identify the presence and nature of disorders of iron metabolism in the body;
- identify the presence of iron deficiency in the body at the preclinical stage;
- conduct differential diagnosis of hypochromic anemia;
- evaluate the effectiveness of the therapy.
Iron Deficiency Anemia Treatment
In all cases of iron deficiency anemia, it is necessary to establish the immediate cause of this condition and, if possible, eliminate it (most often eliminate the source of blood loss or treat the underlying disease complicated by sideropenia).
Treatment of iron deficiency anemia should be pathogenetically substantiated, comprehensive and aimed not only at eliminating anemia as a symptom, but also at eliminating iron deficiency and replenishing its reserves in the body.
Iron deficiency anemia treatment program:
- elimination of the cause of iron deficiency anemia;
- medical nutrition;
- prevention of relapse.
Patients with iron deficiency anemia are recommended a varied diet, including meat products (veal, liver) and plant products (beans, soy, parsley, peas, spinach, dried apricots, prunes, pomegranates, raisins, rice, buckwheat, bread). However, it is impossible to achieve an antianemic effect only with diet. Even if the patient eats high-calorie foods containing animal protein, iron salts, vitamins, trace elements, iron absorption can be achieved no more than 3-5 mg per day. It is necessary to use iron preparations. At present, the doctor has at his disposal a large arsenal of iron medications, characterized by different composition and properties, the amount of iron contained in them, the presence of additional components that affect the pharmacokinetics of the drug, and various dosage forms.
According to the recommendations developed by WHO, when prescribing iron preparations, preference is given to preparations containing ferrous iron. The daily dose in adults should reach 2 mg / kg of elemental iron. The total duration of treatment is at least three months (sometimes up to 4-6 months). An ideal iron-containing preparation should have a minimal amount of side effects, have a simple application schedule, the best ratio of effectiveness / price, optimal iron content, it is desirable to have factors that enhance absorption and stimulate hematopoiesis.
Indications for parenteral administration of iron preparations occur with intolerance to all oral drugs, malabsorption (ulcerative colitis, enteritis), gastric ulcer and duodenal ulcer during exacerbation, with severe anemia and the vital need for rapid replacement of iron deficiency. The effectiveness of iron preparations is judged by changes in laboratory parameters in dynamics. By the 5-7th day of treatment, the number of reticulocytes increases by 1.5-2 times in comparison with the initial data. Starting from the 10th day of therapy, the hemoglobin content increases.
Given the prooxidant and lysosomotropic effects of iron preparations, their parenteral administration can be combined with intravenous drip of reopoliglyukin (400 ml once a week), which allows the cell to be protected and macrophages not to be overloaded with iron. Considering significant changes in the functional state of the erythrocyte membrane, activation of lipid peroxidation, and a decrease in the antioxidant protection of red blood cells in case of iron deficiency anemia, it is necessary to introduce antioxidants, membrane stabilizers, cytoprotectors, antihypoxants such as a-tocopherol to 100-150 mg per day (or ascorutin, vitamin A, vitamin C, lipostabil, methionine, mildronate, etc.), as well as combine with vitamins B1, B2, B6, B15, lipoic acid. In some cases, the use of ceruloplasmin is advisable.