RCHR (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical protocols of the Ministry of Health of the Republic of Kazakhstan - 2013

Other iron deficiency anemias (D50.8)

Pediatric hematology, Pediatrics

general information

Short description

Approved by the minutes of the meeting
Expert Commission on Health Development of the Ministry of Health of the Republic of Kazakhstan
No. 23 from 12/12/2013

ZhDA- an acquired disease from the group of deficiency anemias, occurs with iron deficiency, accompanied by microcytic, hypochromic, normoregenerative anemia, the clinical manifestations of which are a combination of sideropenic and anemic syndromes.

Protocol name - Iron deficiency anemia in children

Protocol code:

ICD-10 code(s)
D50 Iron deficiency anemia
D50.0 Chronic posthemorrhagic anemia

Abbreviations used in the protocol:

ACB anemia with chronic diseases
WHO World Health Organization

HPA hydroside polymaltose complex
IDA iron deficiency anemia

Gastrointestinal tract gastrointestinal tract

LID latent iron deficiency
MCHC average concentration of hemoglobin in a red blood cell

NTZ transferrin saturation coefficient with iron
OZhSS total iron-binding capacity

SJ serum iron
SF serum ferritin

CPU color index

EGDS esophagogastroduodenoscopy

Hb hemoglobin

MCV mean red blood cell volume

RDW degree of erythrocyte anisocyotosis

Date of development of the protocol: year 2013

Protocol users: doctors general practice, pediatricians, hematologists

Classification

Clinical classification:
I degree (mild) - Hb level 110-90 g/l;
II degree (average) - Hb level 90-70 g/l;
III degree (severe) - Hb level less than 70 g/l.

Diagnostics

List of basic and additional diagnostic measures:
- Expanded CBC, reticulocytes
- Serum iron concentration
- Total iron binding capacity of serum
- Serum ferritin content
- List of additional diagnostic measures:
-MCV
- MCH
-MCHC
-RDW
- coefficient of transferrin saturation with iron
- determination of soluble transferrin receptors

Diagnostic criteria:
Clinical manifestations IDA is a combination of two syndromes: sideropenic and anemic.
For sideropenic syndrome
- skin changes: dryness, appearance of small pigment spots of “café au lait” color;
- changes in the mucous membranes: “jams” in the corner of the mouth, glossitis, atrophic gastritis and esophagitis;
- dyspeptic symptoms from the gastrointestinal tract;
- hair changes - bifurcation of the tip, fragility and loss up to alopecia areata;
- changes in nails - transverse striation of nails thumbs hands (in severe cases and legs), fragility, delamination into plates;
- change in the sense of smell - the patient’s addiction to the strong smells of varnish, acetone paint, car exhaust, concentrated perfumes;
- changes in taste - the patient’s addiction to clay, chalk, raw meat, dough, dumplings, etc.;
- pain in the calf muscles.

It is believed that the presence of 4 or more of the symptoms listed above is pathognomonic for latent iron deficiency (LDI) and IDA.

For anemic syndrome The following symptoms are typical:
- loss of appetite;
- noise in ears;
- flashing of flies before the eyes;
- poor tolerance to physical activity;
- weakness, lethargy, dizziness, irritability;
- fainting;
- shortness of breath;
- decreased performance;
- decrease in cognitive functions;
- decreased quality of life;
- pallor of the skin and visible mucous membranes;
- change in muscle tone in the form of a tendency to hypotension, muscle hypotonia Bladder with the development of urinary incontinence;
- expansion of the boundaries of the heart;
- muffled heart sounds;
- tachycardia;
c- istolic murmur at the apex of the heart.

Criteria laboratory diagnostics diseases

There are 3 possibilities for laboratory diagnosis of IDA:

A CBC performed by the “manual” method - a decrease in Hb concentration (less than 110 g/l), a slight decrease in the number of red blood cells (less than 3.8 x 1012/l), a decrease in CP (less than 0.85), an increase in ESR (more than 10-12 mm/hour), normal reticulocyte content (10-20‰). Additionally, the laboratory doctor describes anisocytosis and poikilocytosis of erythrocytes. IDA is a microcytic, hypochromic, normoregenerative anemia.

CBC performed on an automatic blood cell analyzer - the average erythrocyte volume - MCV (less than 80 fl), the average Hb content in an erythrocyte - MCH (less than 26 pg), the average Hb concentration in an erythrocyte - MCHC (less than 320 g/l), increases degree of anisocytosis of erythrocytes - RDW (more than 14%).

Biochemical blood test - decreased serum iron concentration (less than 12.5 µmol/l), increased total iron-binding capacity of serum (more than 69 µmol/l), decreased transferrin saturation coefficient with iron (less than 17%), decreased serum ferritin (less than 30 ng/l). ml). IN last years it became possible to determine soluble transferrin receptors (sTFR), the number of which increases under conditions of iron deficiency (more than 2.9 μg/ml).

Treatment abroad

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Treatment

Treatment goals:
- normalization of blood counts;
- relief of anemic, sideropenic syndromes

Treatment tactics

Non-drug treatment
- Elimination of etiological factors;
- Rational therapeutic nutrition(for newborns - breast natural feeding, and in the absence of milk from the mother - adapted milk formulas fortified with iron. Timely introduction of complementary foods, meat, offal, buckwheat and oatmeal, fruit and vegetable purees, hard cheeses; reducing the intake of phosphates, tannin, calcium, which impair the absorption of iron).

Drug treatment
Currently, our country uses a therapeutic plan for the treatment of IDA with oral iron preparations, the daily doses of which are presented in the table.
Age-specific therapeutic doses of oral iron preparations for the treatment of IDA in children (WHO, 1989)


Principles of rational therapy for IDA in children

Treatment with iron supplements is recommended under the supervision of a physician. It is recommended to prescribe iron supplements to children after consulting a pediatrician.

Iron supplements should not be prescribed to children against the background of inflammatory processes (ARVI, sore throat, pneumonia, etc.), since in this case iron accumulates at the site of infection and is not used for its intended purpose.

Iron deficiency anemia should be treated mainly with drugs for internal use.

Iron must be divalent, since it is divalent iron that is absorbed.

The use of iron supplements should be combined with optimization of the diet, with the mandatory introduction of meat dishes into the menu.

For maximum absorption of iron, the drug should be taken 0.5-1 hour before meals with water. If side effects occur, you can take the medicine with food. Iron is absorbed worst of all if the drug is taken after meals.

Oral iron supplements should be taken at least 4 hours apart.

Tablets and dragees containing iron do not chew!

The inclusion of ascorbic acid in complex iron preparations improves the absorption of iron (as an antioxidant, ascorbic acid prevents the conversion of Fe-II ions into Fe-III, which are not absorbed into the gastrointestinal tract) and makes it possible to reduce the prescribed dose. Iron absorption also increases in the presence of fructose, succinic acid

You cannot combine taking an iron supplement with substances that inhibit its absorption: milk (calcium salts), tea (tannin), herbal products (phytates and chelates), a number of medications (tetracycline, antacids, H2 receptor blockers, proton pump inhibitors).

Taking combination drugs that, along with iron, contain copper, cobalt, folic acid, vitamin B12 or liver extract, makes it extremely difficult to control the effectiveness of iron therapy (due to the hematopoietic activity of these substances).

The average duration of treatment for IDA is from 4 to 8 weeks. Treatment with an iron supplement should be continued after the relief of IDA to restore tissue and stored iron. The duration of the maintenance course is determined by the degree and duration of iron deficiency (ID) and the level of SF.

In the treatment of IDA, vitamin B12, folic acid, vitamin B6, which are pathogenetically in no way related to iron deficiency, should not be used.

The ineffectiveness of IDA therapy with oral iron supplements requires a revision of the diagnosis (often the diagnosis of IDA is established in a patient with anemia of a chronic disease in which treatment with iron supplements is ineffective), checking the patient’s compliance with the doctor’s prescriptions in the dosage and timing of treatment. Iron malabsorption is very rare.

Parenteral administration of iron supplements is indicated only: for the syndrome of impaired intestinal absorption and conditions after extensive resection of the small intestine, nonspecific ulcerative colitis, severe chronic enterocolitis and dysbiosis, intolerance to oral iron supplements. Limiting parenteral administration is associated with a high risk of developing local and systemic adverse reactions. In addition, parenteral use of iron supplements is much more expensive than oral therapy due to the labor costs of medical personnel and the higher cost of the dosage form. Parenteral administration of iron supplements should be produce only in a hospital!

Simultaneous administration of iron preparations orally and parenterally (intramuscularly and/or intravenously) should be completely excluded!
- Red blood cell transfusions should not be used in the treatment of IDA. Donor iron is not reutilized by the recipient's body and remains in the hemosiderin of macrophages. Transfer possible dangerous infections through donated blood. Exceptions that allow transfusion of donor red blood cells are: 1) severe hemodynamic disturbances; 2) upcoming additional blood loss (childbirth, surgery) with severe anemia (hemoglobin less than 70 g/l); 3) an iron supplement that meets modern requirements must be accessible and cheap.

Preparations containing ferric iron Fe(III)

Ferric iron is practically not absorbed in the gastrointestinal tract. However, complex organic compounds of Fe (III) with a number of amino acids and maltose are significantly less toxic than Fe (II), but no less effective. Immobilization of Fe (III) on amino acids ensures its resistance to hydrolysis in the gastrointestinal tract and high bioavailability due to its slow release medicinal substance and its more complete absorption, as well as the absence of dyspeptic symptoms.

Complications of treatment

The use of iron salt preparations may be accompanied by complications in the form of gastrointestinal toxicity with the development of symptoms such as pain in the epigastric region, constipation, diarrhea, nausea, and vomiting. This leads to low compliance with treatment of IDA with iron salt preparations - 30-35% of patients who started treatment refuse to continue it. Overdose and even poisoning with iron salt preparations are possible due to passive uncontrolled absorption.

Other types of treatment - no
Surgery - no

Prevention

The primary prevention of iron deficiency is proper, nutritious nutrition.

Secondary prevention of iron deficiency is the active detection of LVAD and VA during medical examinations, medical examinations, and when visiting a doctor.

Further management: the prognosis of the disease is favorable, cure should occur in 100% of cases.

So-called “relapses” of the disease are possible when:
- use low doses iron supplements;
- ineffectiveness of oral iron supplements, which is rare;
- reducing the duration of treatment for patients;
- treatment of patients with chronic posthemorrhagic anemia with an unidentified and unresolved source of blood loss.

Information

Sources and literature

1. Minutes of meetings of the Expert Commission on Health Development of the Ministry of Health of the Republic of Kazakhstan, 2013
   1. List of references: 1. International statistical classification of diseases and health-related problems. Tenth revision (ICD-10). Geneva: WHO; 1995. vol. 1-2 2. WHO, UNICEF, UNU.IDA: prevention, assessment and control: report of a joint WHO/UNICEF/UNU consultation. Geneva: WHO, 1998. 3. World Health Organization. Iron deficiency anemia: assessment, prevention and control. A guide for program managers. Geneva; 2001; (WHO/NHD/01.3). 4. Hertl M. Differential diagnosis in pediatrics. M.: Medicine; 1990. vol.2. 510 pp. 5. Kon I.Ya., Kurkova V.I. The role of nutritional factors in the development of iron deficiency anemia in young children. In the book: Kislyak N.S. et al. (ed.) Iron deficiency and iron deficiency anemia. M.: Slavic dialogue; 2001. 87-98. 6. Rumyantsev A.G., Korovina N.A., Chernov V.M. and others. Diagnosis and treatment of iron deficiency anemia in children. Toolkit for doctors. M.; 2004. 45 p. 7. Report on the state of health of children in the Russian Federation. M.; 2003. 96 p. 8. Ozhegov E.A. Optimizing the treatment of iron deficiency anemia in children and adolescents. Abstract of thesis... Candidate of Medical Sciences. M.; 2005. 9. Krasilnikova M.V. Iron deficiency conditions in adolescents: frequency characteristics, structure and secondary prevention. Abstract of thesis. Candidate of Medical Sciences M.; 2006. 10. Anemia – a hidden epidemic. Per. from English M.: Mega Pro; 2004. 11. Recommendations to prevent and control iron deficiency in the United States. Centers for Disease Control and Prevention. MMWR Recomm Rep 1998; 47 (RR-3): 1-29. 12. Omarova K.O., Bazarbaeva A.A., Kurmanbekova S.K. Iron deficiency anemia in children. Guidelines. Almaty. 2009. 13. Standards for providing specialized care to children and adolescents with hematological and oncological diseases. Moscow. 2009. 14. Krivenok V. Necessary component of treatment of iron deficiency anemia // Pharmacist. – 2002. - No. 18. – P.44. 15. Korovina N.A., Zaplatnikov A.L., Zakharova I.N. Iron deficiency anemia in children. Moscow, 1999, pp. 25-27. 16. Vidal reference book. Medicines in Kazakhstan: Directory M.: Astra Pharm Service, 2008. – 944 p. 17. Uzhegova E.B. Iron-deficiency anemia. Educational and methodological manual. - Almaty. 2008. – P.22-24. 18. Fairbanks V.F., Beutler E.: Iron deficiency // In Williams Hematology, Fifth Editor, New York, McGraw-Hill; 1999, P.490-510.

Information

List of protocol developers
Omarova K.O. - Doctor of Medical Sciences, Professor, Scientific Center of Pediatrics and Pediatric Surgery of the Ministry of Health of the Republic of Kazakhstan.

Conflict of interest
The protocol developer has no financial or other interests that could influence the conclusion, and is not related to the sale, production or distribution of drugs, equipment, etc., specified in the protocol.

Reviewers
Kurmanbekova S.K. - Professor of the Department of Internship and Residency in Pediatrics of the Kazakh National medical university named after S.D. Asfendiyarov

Conditions for reviewing the protocol: after 3 years from the date of publication

Attached files

Attention!

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FEDERAL AGENCY FOR TECHNICAL REGULATION AND METROLOGY

NATIONAL

STANDARD

RUSSIAN

FEDERATION

Official publication

Standardinform

Preface

Goals and principles of standardization in Russian Federation installed Federal law dated December 27, 2002 No. 184-FZ “On technical regulation”, and the rules for the application of national standards of the Russian Federation - GOST R 1.0-2004 “Standardization in the Russian Federation. Basic provisions"

Standard information

1 DEVELOPED by Interregional public organization promoting standardization and quality improvement medical care

2 INTRODUCED by the Technical Committee for Standardization TC 466 “Medical Technologies”

3 APPROVED AND ENTERED INTO EFFECT by Order of the Federal Agency for Technical Regulation and Metrology dated December 18, 2008 No. 498-st

By order of the Federal Agency for Technical Regulation and Metrology dated December 31, 2008 No. 4196, the implementation date was postponed to January 1, 2010.

4 INTRODUCED FOR THE FIRST TIME

Information about changes to this standard is published in the annually published information index “National Standards”, and the text of changes and amendments is published in the monthly published information index “National Standards”. In case of revision (replacement) or cancellation of this standard, the corresponding notice will be published in the monthly published information index “National Standards”. Relevant information, notifications and texts are also posted in the public information system - on the official website of the Federal Agency for Technical Regulation and Metrology on the Internet

© Standardinform, 2009

This standard cannot be fully or partially reproduced, replicated or distributed as an official publication without permission from the Federal Agency for Technical Regulation and Metrology

GOST R 52600.4-2008

for iron deficiency anemia without an obvious source of blood loss, a thorough laboratory and instrumental examination is carried out: x-ray and endoscopic examinations

gastrointestinal tract, etc., aimed at determining the cause of iron deficiency anemia in accordance with the requirements of the diagnostic sections of other patient management protocols.

Iron deficiency anemia in children is characterized by the following features. Anemia in newborns and infants is a consequence of iron deficiency in the mother, not so much during pregnancy, but especially during lactation. In children with a high risk of iron deficiency anemia (high risk is implied by the low socioeconomic status of the child's family, low birth weight (less than 2500 g), feeding only cow's milk during the first year of life), repeated determinations of blood hemoglobin are necessary at 6 and 12 months

Iron deficiency anemia in pregnant women is characterized by the following features. In differential diagnosis, “false anemia” is excluded, which in pregnant women can be a consequence of hydremia (blood dilution). In this case, to clarify the diagnosis it is necessary:

Examine the volume of circulating blood;

Assess the ratio of the volume of circulating plasma to the volume of circulating erythrocytes;

Determine hypochromia of erythrocytes (an important sign);

Determine serum iron content (an important sign);

Determine the ferritin level in the blood;

Determine the content of soluble transferrin receptors.

Anemia in pregnant women is also observed with nephropathy of pregnancy (preeclampsia), with chronic urinary tract infections, but in these cases it refers to anemia of chronic diseases.

Iron deficiency anemia in older people is characterized by the following features. Diagnostic studies are aimed at excluding (detection) microbleedings from the gastrointestinal tract (erosions and gastric ulcers, polyposis, hemorrhoids, etc.), oncological pathology in the intestines, dysbacteriosis, diverticulosis (competitive consumption of iron by bacteria), nutritional deficiency of iron, malabsorption ( for example, when chronic pancreatitis), blood loss from oral cavity due to problems with dentures. In differential diagnosis, B 12 deficiency anemia and anemia of chronic diseases are excluded.

Iron deficiency anemia, which cannot be corrected for a long time with adequate treatment, has the following features. In case of persistent anemia, especially in combination with low-grade fever, lymphadenopathy, and causeless sweating, it is necessary to diagnose the absence of tuberculosis.

Diagnostic stage errors:

Anamnesis and physical examination were not completed;

The cause of iron deficiency anemia has not been established;

Baseline serum iron and ferritin studies were not performed;

Initial determination of peripheral blood reticulocytes was not performed;

Serum iron testing was carried out after taking iron supplements.

3.3 General approaches to the treatment of iron deficiency anemia

Principles of treatment of iron deficiency anemia:

Diet cannot cure iron deficiency anemia.

The use of medications that strictly correspond to a specific pathogenetic variant of anemia, i.e., the use of only iron supplements.

The use of predominantly oral drugs.

Treatment is adequate with high daily doses of one drug and is well tolerated.

Prescription of erythrocyte transfusion only for lifelong indications, including patients of older age groups with progressive angina pectoris, circulatory decompensation and cerebral hypoxic disorders.

Assessment of the treatment effect based on clinical and laboratory signs, including reticulocyte crisis.

The use of drugs with an optimal cost/effectiveness ratio allows minimizing treatment costs.

Rational therapeutic tactics involve starting treatment from the moment iron deficiency anemia is detected until complete clinical and hematological remission is achieved; if necessary, conduct maintenance (preventive) therapy.

Elimination of the causes (diseases) of iron deficiency anemia.

The basis of replacement therapy for iron deficiency in the treatment of iron deficiency anemia is iron preparations. Currently, two groups of iron preparations are used - those containing

pressing divalent and trivalent iron. Due to the fact that iron from most modern iron-containing preparations is well absorbed by the intestine, in the vast majority of cases it is possible to use iron preparations orally. Parenteral iron supplements are prescribed only for special indications, which include:

The presence of intestinal pathology with malabsorption (severe enteritis, malabsorption syndrome, resection of the small intestine, etc.);

Absolute intolerance to iron preparations when taken orally (nausea, vomiting), even when using drugs from different groups, which does not allow further treatment to be continued;

The need to quickly saturate the body with iron, for example, when surgical interventions are planned for patients with iron deficiency anemia;

Treatment of patients with erythropoietin, in which the limiting factor of effectiveness is an insufficient amount of stored and circulating iron.

No more than 10% - 12% of the iron contained in it is absorbed from the dosage form. With severe iron deficiency, the rate of iron absorption can increase threefold. Increased bioavailability of iron is facilitated by the presence of ascorbic and succinic acids, fructose, cysteine ​​and other accelerators, as well as the use of special matrices in a number of drugs that slow down the release of iron in the intestines (level of evidence B). Iron absorption may decrease under the influence of certain substances contained in food (tea tannin, phosphoric acid, phytin, calcium salts, milk), as well as with the simultaneous use of a number of medications (tetracycline drugs, Almagel, phosphalugel, calcium preparations, chloramphenicol, penicillamine, etc. .). These substances do not affect the absorption of iron from the polymaltose complex of iron hydroxide. To reduce the likelihood side effects Iron salts are taken before meals.

Calculation of the daily dose of the drug (DAA) for oral iron supplements is performed using the following formula

where NSD is necessary daily dose divalent or trivalent (non-elementary) iron (in adults - 200 mg per day, in children - 30 - 100 mg per day);

Calculation of the approximate course dose of iron A, mg, prescribed parenterally, can be carried out using the formula, taking into account the patient’s body weight and hemoglobin level, reflecting the degree of iron deficiency

A = M (Hbi - Hb 2) 0.24 + D, (5)

where M is body weight, kg;

Hbi - standard hemoglobin level for body weight less than 35 kg 130 g/l, more than 35 kg - 150 g/l;

Hb 2 - patient's hemoglobin level, g/l;

D - calculated value of iron depot for body weight less than 35 kg - 15 mg/kg, for body weight more than 35 kg - 500 mg.

The optimal daily dose for iron supplements in the treatment of iron deficiency anemia should correspond to the required daily dose and is calculated:

Iron in the composition of iron salt preparations is for children under 3 years old - 5 - 8 mg of ferrous iron per kg of body weight per day, over 3 years old - 100 - 120 mg ferrous iron per day, adults - 200 mg of ferrous iron per day;

Iron in preparations of polymaltose complex of iron hydroxide (ferric iron) for premature babies 2.5 - 5 mg per kg body weight, children under one year - 25 - 50 mg, 1-12 years 50 - 100 mg, over 12 years 100 - 300 mg , adults - 200 - 300 mg.

The use of smaller doses of drugs does not provide an adequate clinical effect. In case of latent iron deficiency or to saturate the depot after the end of the course of therapy, half the therapeutic doses of drugs are used.

For adult patients, no more than 200 mg of iron per day is administered parenterally; for special indications, by drip, up to 500 mg per day. In children, the daily dose is 25 - 50 mg, depending on age, the drug

GOST R 52600.4-2008

inject in a stream, slowly - for at least 10 minutes. Maximum permissible single dose- 7 mg of iron per kg of body weight is administered once a week.

Monitoring the effectiveness of therapy is an essential component of the rational use of iron-containing drugs. In the first days of treatment, an assessment is carried out subjective feelings, on the 5-8th day it is necessary to determine the reticulocyte crisis (2 - 10-fold increase in the number of reticulocytes compared to the initial value). At week 3, the increase in hemoglobin and the number of red blood cells is assessed. The absence of a reticulocyte crisis indicates either an erroneous prescription of the drug or the prescription of an inappropriately small dose.

Normalization of hemoglobin levels and disappearance of hypochromia usually occurs by the end of the first month of treatment (with adequate doses of drugs). However, to saturate the depot, it is recommended to use half the dose of iron-containing drugs for another 4 to 8 weeks. Depot saturation is determined using a complex biochemical research. In the absence of these methods, treatment is carried out empirically.

Among the side effects of oral administration of iron supplements, the most common are dyspeptic disorders (anorexia, metallic taste in the mouth, feeling of fullness in the stomach, pressure in the epigastric region, nausea, vomiting), constipation, and sometimes diarrhea. The development of constipation is associated with the formation of iron sulfide in the intestines, which is an active inhibitor of colon function. In some patients, especially children, when using iron salts, a brownish staining of the tooth enamel occurs. Frequently appearing dark colored stools have no clinical significance.

With parenteral administration of iron preparations, reactions may occur: local - phlebitis, venous spasm, darkening of the skin at the injection site, post-injection abscesses and general - hypotension, chest pain, paresthesia, muscle pain, arthralgia, fever. In case of overdose, iron oversaturation with the development of hemosiderosis is possible. Malignancy is possible at the injection site.

Bivalent iron is very often included in complex vitamin preparations. However, their dose of iron is negligible and therefore cannot be used to treat iron deficiency (level of evidence A).

The most common treatment errors have the following main causes:

Iron supplements are prescribed in inadequate (small) doses;

Treatment is short-term, adequate patient adherence to therapy is not achieved;

Vitamins, biologically active supplements or medications with low iron content are prescribed unreasonably.

Treatment of iron deficiency anemia in some age groups and under various conditions has the following features.

Iron deficiency anemia in children of puberty (juvenile chlorosis) is characterized by the following features. Iron deficiency during the period of rapid growth is a consequence of a reduced iron supply that is not compensated for in the first years of life. An abrupt increase in iron consumption by a rapidly growing organism and the appearance of menstrual blood loss aggravate the relative deficiency. Therefore, during puberty, it is advisable to use dietary prevention of iron deficiency, and if signs of hyposiderosis appear, prescribe iron supplements.

Iron deficiency anemia in menstruating women is characterized by the following features. Simply calculating the approximate amount of iron lost through menstrual blood can help determine the source of blood loss. On average, a woman loses about 50 ml of blood (25 mg of iron) during menstruation, which determines twice the loss of iron compared to men (if distributed over all days of the month, then an additional 1 mg per day). At the same time, it is known that in women suffering from menorrhagia, the amount of blood lost reaches 200 ml or more (100 mg of iron or more), and, therefore, the additional average daily loss of iron is 4 mg or more. In such situations, the loss of iron in 1 month exceeds its possible intake from food by 30 mg, and in one year the deficiency reaches 360 mg.

The rate of progression of anemia during uterine blood loss, in addition to the severity of menorrhagia, is influenced by the initial value of iron reserves, dietary habits, previous pregnancies and lactation, etc. To estimate the volume of blood lost during menstruation, it is necessary to clarify the number of pads a woman changes daily and their characteristics (lately pads with different absorbent properties have been used; a woman chooses her pads depending on the amount of blood loss), the presence of a large number of large clots. Relatively small, “normal” blood loss is considered to be the use of two pads per day, the presence of small (1 - 2 mm in diameter) and a small number of clots.

In cases where the cause of iron deficiency is menstrual blood loss, a single course of replacement therapy is not sufficient, since a relapse will occur after a few months. Therefore, maintenance preventive therapy is carried out, usually individually selecting the dose of the drug using titration. It is recommended to take iron-containing preparations with a high iron content from the first day of menstruation for 7 to 10 days. For some women, it is enough to carry out such maintenance therapy once every quarter or once every six months. A consensus must be reached between the doctor and the patient about the essence of anemia, methods of therapy, and the importance of prevention. All this significantly increases treatment compliance.

Iron deficiency anemia in women during pregnancy and lactation is characterized by the following features. To prevent anemia in this group of patients, combination drugs with a relatively low iron content (30 - 50 mg), including vitamins, including folic acid and vitamin B 12. This type of prophylaxis has been shown to have no effect (level of evidence A). Pregnant women with identified iron deficiency anemia are prescribed medications containing large amounts of iron (100 mg, 2 times a day) for the entire remaining period of pregnancy; during lactation (in the absence of large blood loss during childbirth and menstrual losses and with full compensation of anemia), you can switch to medications with a lower iron content (50 - 100 mg per day). If there is no effect from the therapy, first of all, the adequacy of the prescribed doses is analyzed (perhaps they should be increased), and the woman’s correct fulfillment of the prescribed prescriptions (compliance). In addition, there may be “false anemia” as a consequence of hydremia (blood dilution), often observed in pregnant women (to confirm, it is necessary to examine the volume of circulating blood, evaluate the ratio of the volume of circulating plasma to the volume of circulating red blood cells, hypochromia of red blood cells and serum iron content). Anemia is also observed with nephropathy (preeclampsia), with chronic infections (usually urinary tract); in case of persistent anemia, especially in combination with low-grade fever, lymphadenopathy, causeless sweating, it is necessary to exclude the presence of tuberculosis. In these cases we are talking about anemia of chronic diseases. There are no direct contraindications for the use of parenteral iron supplements in pregnant women, but large-scale studies have not been performed in this group.

Iron deficiency anemia in old age is characterized by the following features. The main forms of anemia in this group of patients are iron deficiency and B 12 deficiency. No specific treatment regimens for anemia are required, and patients usually respond quickly to prescribed therapy. The ineffectiveness of therapy for iron deficiency anemia is often associated with constipation caused by dysbacteriosis and peristalsis disorders. In such cases, lactulose can be added to therapy in an adequate dose of up to 50 - 100 ml; after obtaining a lasting effect, the dose of lactulose is halved.

4 Characteristics of requirements

4.1 Patient model

Nosological form: iron deficiency anemia Stage: any Phase: any

Complication: regardless of complications Code according to ICD-10:050.0

4.1.1 Criteria and signs defining the patient model

The patient's condition must meet the following criteria and characteristics:

Decrease in hemoglobin level below 120 g/l;

Decrease in red blood cell level below 4.2 10 12 /l;

Hypochromia of erythrocytes;

A decrease in one of the indicators of saturation of erythrocytes with hemoglobin (color index (CI) below 0.85, average corpuscular hemoglobin content (MCH) below 24 pg, average hemoglobin concentration in erythrocytes (MCHC) below 30 - 38 g/dl);

A decrease in serum iron levels below 13 µmol/l in men and below 12 µmol/l in women.

4.1.2 Requirements for outpatient diagnostics

The list of medical services (MS) for outpatient diagnostics according to the “Nomenclature of Works and Services in Healthcare” is presented in Table 1.

Table 1 - Outpatient diagnostics

Name of MU Delivery frequency Multiplicity execution Study of the level of leukocytes in the blood Study of platelet levels in the blood Ratio of leukocytes in the blood (blood formula) View a blood smear to analyze abnormal morphology of red blood cells, platelets, and white blood cells Taking blood from a finger Determination of the average content and average concentration of hemoglobin in erythrocytes Cytological examination of a bone marrow smear (bone marrow formula calculation) Histological examination of bone marrow preparations Hematocrit estimation Obtaining a cytological preparation of bone marrow by puncture Obtaining a histological specimen of bone marrow Determination of sideroblasts and siderocytes Study of osmotic resistance of erythrocytes Study of acid resistance of erythrocytes Desferal test Determination of the volume of blood loss through the gastrointestinal tract using radioactive chromium

4.1.3 Characteristics of algorithms and features of non-drug care

Diagnosis of iron deficiency anemia:

Stage 1 - determination (confirmation) of the iron deficiency nature of anemia;

Stage 2 - determining the cause of iron deficiency.

The collection of anamnesis and complaints for diseases of the hematopoietic organs and blood is carried out as follows: first of all, signs of sideropenia are identified, including clarification of the diet (exclusion of vegetarianism and other diets with a low content of iron-containing foods); The possible source of blood loss or increased iron consumption is also clarified.

An objective study of diseases of the hematopoietic and blood organs is aimed at identifying signs in the patient that characterize hyposiderosis and identifying diseases (conditions) with increased iron consumption.

The study of the level of red blood cells, leukocytes, platelets, reticulocyte color index, the ratio of leukocytes in the blood (blood formula), the study of the level of total hemoglobin is aimed at identifying signs of blood diseases that may be accompanied by anemia (see 2nd stage of diagnosis). A decrease in color index is decisive in making a diagnosis of iron deficiency anemia. The results of all studies are analyzed by the doctor together; no single symptom is specific for iron deficiency.

Reviewing a blood smear to analyze abnormalities in the morphology of red blood cells, platelets and white blood cells - the most accurate method for determining the hemoglobin content of red blood cells remains a morphological study of red blood cells. In iron deficiency anemia, a distinct hypochromia is detected, characterized by the presence of a wide clearing in the center of the erythrocyte, which resembles a donut or ring (anulocyte).

Serum iron levels are a mandatory diagnostic test for diagnosing iron deficiency anemia. It is necessary to pay attention to the reasons for false-positive results: failure to comply with the technology of the study; the study is carried out soon after taking (even a single dose) iron supplements; after hemo- and plasma transfusion.

When determining the average hemoglobin content in erythrocytes, the technique used in automatic analyzers is used.

Studies of the level of transferrin and serum ferritin are necessary studies in case of doubt about the form of anemia. Research is carried out as part of a complex of iron metabolism studies. Determination of serum transferrin levels allows one to exclude forms of anemia caused by impaired iron transport (atransferrinemia).

A decrease in serum ferritin levels is the most sensitive and specific laboratory sign of iron deficiency.

The total iron binding capacity of serum reflects the degree of serum starvation and transferrin saturation with iron. Iron deficiency anemia is characterized by an increase in the total iron-binding capacity of serum.

Counting sideroblasts (erythroid cells of the bone marrow with iron granules) allows us to confirm the iron deficiency nature of anemia (their number in patients with iron deficiency anemia is significantly reduced). The study is rarely performed, only in complex differential diagnostic cases.

The study of osmotic and acid resistance of erythrocytes is carried out for differential diagnosis with erythrocyte membranopathies.

Taking blood from a finger and from a peripheral vein is carried out strictly on an empty stomach. Blood collection to study hemostasis is carried out without using a syringe and with a loose tourniquet; it is better to use vacuum tubes.

Determining the cause of iron deficiency.

Stage 2 - determining the cause of iron deficiency is carried out in accordance with the requirements stipulated by other protocols for the management of patients (gastric ulcer, uterine leiomyoma, etc.). In particular, with the help of erythrocytes labeled with radioactive chromium, the fact of blood loss through the gastrointestinal tract is confirmed.

If necessary, cytological and histological examination bone marrow smear, erythrocyte acid resistance test, desferal test.

4.1.4 Requirements for outpatient treatment

The list of medical services (MS) for outpatient treatment according to the “Nomenclature of Works and Services in Healthcare” is presented in Table 2.

Table 2 - Outpatient treatment

Name of MU Delivery frequency Multiplicity of execution Collection of anamnesis and complaints for diseases of the hematopoietic and blood organs Visual examination for diseases of the hematopoietic and blood organs Study of the level of reticulocytes in the blood Determination of color index Study of the level of total hemoglobin in the blood Taking blood from a finger Palpation for diseases of the hematopoietic and blood organs Percussion for diseases of the hematopoietic and blood organs General therapeutic auscultation Determination of the average hemoglobin content in erythrocytes Hematocrit estimation Serum iron level test Testing ferritin levels in the blood Study of serum transferrin level Taking blood from a peripheral vein Study of iron-binding ability of serum Study of the level of red blood cells in the blood

4.1.5 Characteristics of algorithms and features of non-drug care

Collection of anamnesis and complaints for diseases of the hematopoietic and blood organs, physical examination is carried out twice to assess the dynamics in general condition(well-being) of patients. “Small signs” of effectiveness are very important from the point of view of early assessment of the effectiveness of therapy.

The first objective effect of therapy should be a reticulocyte crisis, manifested by a significant - 2-10 times increase in the number of reticulocytes compared to the initial value by the end of the first week of therapy. The absence of a reticulocyte crisis indicates either an erroneous prescription of the drug or the prescription of an inappropriately small dose.

An increase in hemoglobin levels and the number of red blood cells is usually observed in the 3rd week of therapy, later hypochromia and microcytosis disappear. By the 21st - 22nd day of treatment, hemoglobin usually normalizes (with adequate doses), but the depot does not become saturated.

If necessary, determine the level of the color index, the average hemoglobin content in erythrocytes, study the serum iron level, ferritin level, serum transferrin, assess the hematocrit and iron-binding capacity of the serum.

Depot saturation can only be checked using a comprehensive biochemical study. Thus, monitoring the effectiveness of therapy is an essential component of the rational use of iron-containing drugs.

Taking blood from a finger and from a peripheral vein is carried out strictly on an empty stomach. Blood sampling for hemostasis testing is carried out without using a syringe and with a loose tourniquet; it is better to use vacuum tubes.

4.1.6 Requirements for outpatient drug care

Requirements for outpatient drug care are presented in Table 3.

Table 3 - Outpatient medical care

Pharmacotherapeutic group Anatomical and therapeutic chemical group International generic Name appointments Approximate daily dose, mg Equivalent course dose, mg Drugs affecting blood Antianemic drugs Iron (III) hydroxide sucrose complex Iron (III) hydroxide polymaltose complex

4.1.7 Characteristics of algorithms and features of the use of medications

Replacement therapy for iron deficiency is carried out with iron supplements. Currently, two groups of iron preparations are used - containing divalent and trivalent iron, in the vast majority of cases used orally.

One of the drugs is used: iron sulfate (orally), iron (III) hydroxide sucrose complex (intravenously), iron (III) hydroxide polymaltose complex (orally and parenterally).

Some drugs are available in the form of syrups and suspensions, which makes them easier to administer to children. However, here too, the recalculation of the daily dose should be carried out taking into account the iron content per unit volume.

For better tolerance, iron supplements are taken with meals. It must be taken into account that under the influence of certain products and substances contained in food (tea tannin, phosphoric acid, phytin, calcium salts, milk), as well as with the simultaneous use of a number of medications (tetracycline preparations, almagel, phospholugel, calcium preparations, chloramphenicol , penicillamine, etc.) absorption of iron from iron salt preparations may decrease. These substances do not affect the absorption of iron from iron III hydroxide polymaltose complex.

Prescribing iron supplements without recalculating the daily dose is ineffective and leads to the development of false “refractory” (evidence level C).

Iron supplements are prescribed for 3 weeks; after the effect is obtained, the dose of the drug is reduced by 2 times and prescribed for another 3 weeks.

Iron sulfate: the optimal daily dose for iron preparations should correspond to the required daily dose of ferrous iron, which is for children under 3 years old 5 - 8 mg/kg per day, over 3 years old - 100 - 120 mg/day, adults - 200 mg/day ( 100 mg 2 times a day 1 hour before and 2 hours after meals). Duration of treatment is 3 weeks, followed by maintenance therapy (1/2 dose) for at least 3 weeks (level of evidence A).

Iron (III) hydroxide polymaltose complex is a new group of iron preparations containing ferric iron as part of a polymaltose complex. They have no less pronounced effect in terms of the speed of saturation of the body with iron than divalent iron. Ferric iron supplements have virtually no side effects. Used as a solution for intramuscular injection, solution and tablets in accordance with the requirements of the formulary articles for drugs.

Iron (III) hydroxide sucrose complex - for parenteral administration, administer 2.5 ml on the 1st day, 5 ml on the 2nd and 10 ml on the 3rd day, then 10 ml 2 times a week. The dose of the drug is calculated taking into account the degree of anemia, body weight and iron reserves.

Parenteral administration of iron supplements should be used only in the following exceptional cases:

1 area of ​​use............................................... ....1

3 General provisions................................................... .....1

3.1 Classification of iron deficiency anemia....................................4

3.2 General approaches to diagnosing iron deficiency anemia.................................4

3.3 General approaches to the treatment of iron deficiency anemia....................................7

4 Characteristics of requirements...................................................10

4.1 Patient model......................................................... ..10

4.1.1 Criteria and signs defining the patient model....................................10

4.1.2 Requirements for outpatient diagnostics...................................10

4.1.3 Characteristics of algorithms and features of non-drug care. 12

4.1.4 Requirements for outpatient treatment....................................12

4.1.5 Characteristics of algorithms and features of non-drug care. 13

4.1.6 Requirements for outpatient medicinal care................................14

4.1.7 Characteristics of algorithms and features of the use of medications..........14

4.1.8 Requirements for the regime of work, rest, treatment or rehabilitation...................15

4.1.9 Requirements for patient care and ancillary procedures....................................15

4.1.10 Requirements for dietary prescriptions and restrictions....................................15

4.1.11 Features of the patient’s informed voluntary consent when performing

patient management protocol and additional information for the patient and his family members.................................................... ..............16

4.1.12 Rules for changing requirements during protocol implementation and termination

protocol requirements.............................................16

4.1.13 Possible outcomes and their characteristics....................................16

5 Graphical, schematic and tabular representation of the protocol.................................16

5.1 Assessing the effectiveness of therapy with iron-containing drugs..................16

5.2 Some characteristics of tablet forms of iron-containing preparations.......17

5.3 Some characteristics of syrups and other liquid forms of iron-containing preparations. . 17

6 Monitoring................................................... ....18

6.1 Criteria and methodology for monitoring and evaluating the effectiveness of the protocol.... 18

6.2 Principles of randomization....................................................18

6.3 Procedure for assessing and documenting side effects and complications........18

6.4 Interim evaluation and modifications to the protocol....................................18

6.5 Procedure for including and excluding a patient from monitoring....................................19

6.6 Parameters for assessing quality of life when implementing the protocol....................................19

6.7 Estimation of the cost of implementing the protocol and the price of quality..................................19

6.8 Comparison of results...................................................19

6.9 Procedure for generating a report....................................................19

5.2 Some characteristics of tablet forms of iron-containing preparations

Characteristics of tablet forms of iron-containing preparations are given in Table 6.

Table 6 - Tablet forms of iron-containing preparations

Commercial name Composition, release form Special indications for use Aktiferrin Ferrous sulfate + serine Pills Hemofer pro-longatum Ferrous sulfate Maltofer Fall Iron polymalto-zate + folic acid Chewable tablets, 100 mg/0.35 mg Pregnant and lactating women Maltofer Iron polymaltosate Chewable tablets, 100 mg Pregnant and lactating women Sorbifer-Duru- Iron sulfate + ascorbic acid Tablets, 320/60 mg Tardiferon Iron sulfate + mucoporotheose + ascorbic acid Pills Iron sulfate + ascorbic acid + riboflavin + nicotine-mide + pyridoxine + calcium pantathenate Pills Pregnant and lactating women Ferretab Iron fumarate Ferroplex Iron sulfate + ascorbic acid Tablets, 50 mg/30 mg Children and teenagers Iron fumarate Capsules, 350 mg

5.3 Some characteristics of syrups and other liquid forms of iron-containing preparations

The characteristics of syrups and other liquid forms containing iron are given in Table 7.

Table 7 - Syrups and other liquid forms of iron-containing preparations

Commercial name International nonproprietary name Composition, release form Aktiferrin Ferrous sulfate + serine Drops, 30 ml Aktiferrin Ferrous sulfate + serine Syrup, 100 ml Ferric chloride Drops (bottles), 10 and 30 ml Iron gluconate, manganese gluconate, copper gluconate Mixture for preparing a solution in ampoules 50 in 1 ampoule Maltofer Iron polymaltosate Solution for internal use (drops), 30 ml 50 in 1 ml Fe* ++ Maltofer Iron polymaltosate Syrup, 150 ml 10 in 1 ml Fe~ + Ferrum Lek Iron polymaltosate Syrup, 100 ml 10 in 1 ml Fe~ +

Appendix A (informative) Unified scale for assessing the strength of evidence

feasibility of using medical technologies...................20

Appendix B (for reference) Some indicators of iron metabolism depending on its degree

deficit........................................................ 20

Appendix B (informative) EQ-5D Questionnaire....................................21

Appendix D (for reference) Patient card form....................................27

Bibliography................................................. .......29

GOST R 52600.4-2008

NATIONAL STANDARD OF THE RUSSIAN FEDERATION

Protocol for the management of patients with IRON DEFICIENCY ANEMIA

Protocol for patient's management. Iron deficiency anemia

Date of introduction - 2010-01-01

1 area of ​​use

This standard establishes the types, volume and quality indicators of medical care for patients with iron deficiency anemia.

This standard is intended for use by medical organizations and institutions of federal, territorial and municipal health care authorities, compulsory and voluntary health insurance systems, and other medical organizations of various organizational and legal forms of activity aimed at providing medical care.

2 Normative references

This standard uses normative reference to the following standard:

GOST R 52600.0-2006 Protocols for the management of patients. General provisions

Note - When using this standard, it is advisable to check the validity of the reference standards in the public information system - on the official website of the Federal Agency for Technical Regulation and Metrology on the Internet or according to the annually published information index “National Standards”, which was published as of January 1 of the current year , and according to the corresponding monthly information indexes published in the current year. If the reference standard is replaced (changed), then when using this standard you should be guided by the replacing (changed) standard. If the reference standard is canceled without replacement, then the provision in which a reference is made to it is applied in the part that does not affect this reference.

3 General provisions

The “Iron Deficiency Anemia” patient management protocol was developed to solve the following problems:

Definitions of the range of diagnostic and medical procedures services provided to patients with iron deficiency anemia;

Definition of algorithms for diagnosis and treatment of iron deficiency anemia;

Establishment of uniform requirements for the procedure for prevention, diagnosis and treatment of patients with iron deficiency anemia;

Unification of calculations of the cost of medical care, development of basic compulsory health insurance programs and tariffs for medical services and optimization of the system of mutual settlements between territories for medical care provided to patients with iron deficiency anemia;

Official publication

Formation of licensing requirements and conditions for carrying out medical activities;

Definitions of formulary entries for drugs used to treat iron deficiency anemia;

Monitoring the volume, accessibility and quality of medical care provided to a patient in a medical institution within the framework of state guarantees of providing citizens with free medical care.

This standard uses a unified scale for assessing the strength of evidence of the use of medical technologies and data in accordance with GOST R 52600.0 (see Appendix A).

Anemia from a clinical position is considered to be a decrease in the concentration of hemoglobin per unit volume of blood, often accompanied by a decrease in the number (concentration) of red blood cells per unit volume of blood. Iron deficiency anemia syndrome is characterized by a weakening of erythropoiesis due to iron deficiency, due to a discrepancy between the supply and consumption (consumption, loss) of iron, a decrease in the filling of hemoglobin with iron, followed by a decrease in the hemoglobin content in the erythrocyte.

In accordance with the International Statistical Classification of Diseases, Injuries and Conditions Affecting Health, 10th revision, the following forms of anemia associated with iron deficiency are distinguished:

D50 Iron deficiency anemia (asiderotic, sideropenic, hypochromic);

D50.0 Iron deficiency anemia associated with chronic blood loss (chronic posthemorrhagic anemia);

D50.1 Sideropenic dysphagia (Kelly-Patterson and Plummer-Vinson syndromes);

D50.8 Other iron deficiency anemia;

D50.9 Iron deficiency anemia, unspecified.

According to statistics, iron deficiency anemia ranks first among the 38 most common human diseases. Of all forms of anemia, it is the most common: 70% - 80% of all diagnosed cases of anemia. Around 700 million people worldwide suffer from iron deficiency anemia. In the Russian Federation, iron deficiency anemia is detected in 6% - 30% of the population.

Risk groups for the development of iron deficiency anemia are:

Newborns;

Children of puberty;

Menstruating women;

Women during pregnancy and lactation;

Patients of older age groups.

A high risk of anemia occurs with a low socio-economic status of the family, donorship, diet with limited iron intake, in children - with a low birth weight of the child (less than 2500 g), and feeding only cow's milk during the first year of life.

Iron deficiency anemia is caused by a discrepancy between the body's need for iron and its supply: in various diseases and conditions accompanied by minimal to significant blood loss, including frequent blood sampling and long-term donation. The causes of iron deficiency anemia are:

Increased need for iron (during the period of body growth, pregnancy, lactation);

Impaired absorption of iron;

Insufficient intake of iron from food (vegetarianism, fasting).

A rare cause of iron deficiency anemia is congenital iron deficiency.

The main diseases and conditions that may be accompanied by iron deficiency anemia:

Pregnancy;

Crohn's disease;

Vegetarianism;

Helminthiases;

Haemorrhoids;

Hemorrhagic esophagitis, gastritis;

Children who are bottle-fed with formulas lacking iron;

Diverticulosis and diverticular bowel disease;

Dysfunctional uterine bleeding;

Menorrhagia;

GOST R 52600.4-2008

Uterine fibroids;

Nonspecific ulcerative colitis;

Operations and injuries with large blood loss;

Tumors of the stomach and intestines;

Early ligation of the umbilical cord and disruption of the placental blood supply;

Endometriosis;

Enteritis;

Duodenal or stomach ulcer;

Iatrogenic causes (donation, hemodialysis, frequent blood draws for research).

It should be borne in mind that in many cases not one, but several diseases and/or conditions can

be causes or risk factors for the development of iron deficiency anemia.

The pathogenesis of iron deficiency anemia is associated with the physiological role of iron in the body and its participation in the processes of tissue respiration. Iron is part of heme, a compound that can reversibly bind oxygen. Heme is the non-protein part of the hemoglobin and myoglobin molecule. It binds oxygen, which, in particular, is necessary for contractile processes in muscles. In addition, heme is an integral part of tissue oxidative enzymes - cytochromes, catalase and peroxidase. The proteins ferritin and hemosiderin are of primary importance in the deposition of iron in the body. The transport of iron in the body is carried out by the protein transferrin. The body can only to a small extent regulate the intake of iron from food and does not control its expenditure. With a negative balance of iron metabolism, iron is first consumed from the depot (latent iron deficiency), then tissue iron deficiency occurs, manifested by impaired enzymatic activity and respiratory function of tissues, and only later does iron deficiency anemia develop.

The clinical picture of iron deficiency anemia is varied and is caused by sideropenic (iron deficiency) and anemic syndromes.

Sideropenic syndrome (hyposiderosis) is associated with tissue deficiency of iron, which is necessary for cell functioning. It is necessary to distinguish between hyposiderosis without anemia (subcompensated stage) and hyposiderosis accompanying anemia. There are 4 main groups of organs in which the manifestations of hyposiderosis are most pronounced:

Skin, skin appendages and mucous membranes;

Gastrointestinal tract;

Nervous system (increased fatigue, tinnitus, dizziness, headaches, decreased intellectual capabilities);

Cardiovascular system (tachycardia, diastolic dysfunction).

Symptoms of sideropenia in patients with iron deficiency anemia, in descending order of frequency of occurrence, are as follows:

Dry skin, forcing women to constantly use creams;

Brittle and layered nails, there is no way to grow nails, they have to be cut very short;

Transverse striations of the nails, the nails become flat, sometimes taking on a concave “spoon-shaped” shape (koilonychia);

Splitting of hair ends, women are worried about the inability to grow hair;

Perversion of taste in the form of an irrepressible desire to eat chalk, toothpaste, ashes, paints, earth, etc. (pathophagy);

Unusual addiction to certain odors, more often acetone, gasoline (pathosmia); On the streets of older age groups there is often no perversion of appetite and sense of smell;

Violation of the integrity of the epidermis is rarely observed, in particular, in approximately 5% - 10% of patients, angular stomatitis (jams) appears: ulcerations, cracks with an inflammatory shaft in the corners of the mouth (can also be a sign of hypovitaminosis B 2);

Only some patients note a burning sensation of the tongue, signs of glossitis;

An extremely rare symptom may be impaired swallowing function due to the formation of esophageal septa (sideropenic dysphagia - Plummer-Vinson syndrome);

The symptoms of gastritis (severity, pain) are not as pronounced as with gastritis of other origins;

Dysuria and urinary incontinence when coughing, laughing, and nocturnal enuresis are sometimes observed in girls, less often in adult women.

The presence of iron deficiency anemia causes neuropsychiatric functional disorders in children. According to special studies, with iron deficiency anemia in children of the first

year of life, the index of intellectual development at 12 months is 96 (102 in the control), and 89 of physical development (100 in the control). There is an inverse correlation between physical and mental development, severity and duration of anemia.

Anemic syndrome due to iron deficiency is manifested by nonspecific symptoms: dizziness, headaches, tinnitus, flickering of spots before the eyes, weakness, fatigue, decreased performance, chronic fatigue, pallor of the skin and mucous membranes, palpitations, shortness of breath with physical activity. Some symptoms may be due not so much to anemia as to sideropenia.

3.1 Classification of iron deficiency anemia

There is no generally accepted classification of iron deficiency anemia. Based on the severity of clinical manifestations, the following stages of development of iron deficiency are conventionally distinguished:

Stage 1 - loss of iron exceeds its supply, gradual depletion of reserves, absorption in the intestine increases compensatoryly.

Stage 2 - depletion of iron reserves (serum iron level below 13 µmol/l in men and below 12 µmol/l in women, transferrin saturation - below 16%) interferes with normal erythropoiesis, erythropoiesis begins to fall.

Stage 3 - development of mild anemia (100 - 120 g/l hemoglobin, compensated) with a slight decrease in the color index and other indices of saturation of erythrocytes with hemoglobin.

Stage 4 - severe (less than 100 g/l hemoglobin, subcompensated) anemia with a clear decrease in the saturation of erythrocytes with hemoglobin.

Stage 5 - severe anemia (60 - 80 g/l hemoglobin) with circulatory disorders and tissue hypoxia.

3.2 General approaches to diagnosing iron deficiency anemia

The diagnostic examination process can be conditionally presented in the form of the following sequential stages:

Identification of the anemic syndrome itself;

Determination (confirmation) of the iron deficiency nature of anemia;

Search for the cause of the disease underlying iron deficiency in a given patient.

Detection of anemic syndrome - determination of decreased serum hemoglobin levels

blood - performed in patients with clinical signs disease, and may also be incidental during a routine peripheral blood test performed in connection with another disease or a screening study.

Normal blood hemoglobin levels: the lower threshold for an adult is 120 g/l (7.5 mmol/l) for women and 130 g/l (8.1 mmol/l) for men.

Establishing the iron deficiency nature of anemia is the determination of clinical manifestations of sideropenia, morphological signs of iron deficiency in erythrocytes, a decrease in serum iron levels, and iron reserves in the body.

At this stage of diagnosing iron deficiency anemia, a thorough laboratory study is carried out, which necessarily includes: determining the level of hemoglobin, the number of red blood cells, platelets, reticulocytes, leukocyte formula, calculating the color index or average hemoglobin content in a red blood cell, viewing a blood smear to determine abnormal forms of red blood cells and their saturation with hemoglobin, leukocytes and cellular inclusions.

Determination of iron reserves

The color index (CI) is calculated using the formula

With iron deficiency, the color index, as a rule, becomes below 0.85 (normal 1.0). Errors in calculating the color index are associated, first of all, with incorrect determination of hemoglobin and the number of red blood cells. It is often necessary to observe in the results of a blood test that the color indicator is normal, and the red blood cells contain little hemoglobin - that is, there is an inadequate determination of this important indicator.

B is the number of red blood cells in 1 liter of blood.

For iron deficiency, the MNI is below 24 g.

The average hemoglobin concentration in erythrocytes (MCHC) is calculated using the formula

MCHC = -, (3)

Ht - hematocrit, %.

The normal MCHC value is 30 - 38 g/dl.

The most accurate method for assessing the hemoglobin content in erythrocytes remains a morphological study of erythrocytes. In iron deficiency anemia, a distinct hypochromia is detected, characterized by the presence of a wide clearing in the center of the erythrocyte, which resembles a ring (anulocyte). Normally, the ratio of the diameter of the central clearing and peripheral “darkening” in the erythrocyte is approximately 1:1, with hypochromia - 2-3:1. In the blood smear of patients with iron deficiency anemia, microcytes predominate - red blood cells of reduced size; anisocytosis (unequal sizes) and poikilocytosis (various forms) of red blood cells are noted. In iron deficiency anemia, target-like red blood cells can also be detected, although their number is 0.1% - 1.0% of the total number of cells.

The number of siderocytes (erythrocytes with iron granules, revealed by special staining) is sharply reduced compared to the norm, up to their complete absence. The content of reticulocytes in the blood, as a rule, is within normal limits, with the exception of cases of severe blood loss due to corresponding pathologies (excessive nasal and uterine bleeding) or during treatment with iron supplements (in these cases it may increase). The number of leukocytes and platelets is usually unchanged. Some patients may experience thrombocytosis, which disappears after correction of anemia.

Morphological examination of the bone marrow for diagnosing iron deficiency anemia can only be important with special staining for iron to count sideroblasts (erythroid cells of the bone marrow with iron granules), the number of which is significantly reduced in patients with this anemia.

To varying degrees, iron reserves in the body can be determined by the following methods:

Serum iron testing;

Study of the total iron-binding capacity of serum with calculation of the latent iron-binding capacity of serum;

Testing the level of ferritin in the blood;

Transferrin saturation study;

Desferal test.

Normal values ​​of serum iron in men are 13 - 30 µmol/l, in women - 12 - 25 µmol/l; with iron deficiency, the value of this indicator is reduced, often significantly. When analyzing the results, one should take into account the susceptibility of serum iron concentration to diurnal fluctuations (in morning hours iron levels are higher), as well as other influences (menstrual cycle, pregnancy, contraceptives, diet, blood transfusion, taking iron-containing drugs, etc.).

When conducting these studies, strict adherence to the methodology is required. When preparing glass tubes for testing serum iron levels, they must be treated hydrochloric acid and wash with bidistilled water, since the use of ordinary distilled water for washing, containing a small amount of iron, affects the results of the study. Drying cabinets should not be used to dry test tubes: when heated, a small amount of iron gets into the dishes from their walls. Immediately after drawing blood, the tube must be closed with a stopper or cap made of aluminum foil or a special waxed membrane, since during centrifugation fine metal dust gets into it. Plastic tubes can also be used, but the requirements for obtaining and processing blood remain important in this case. The exception is vacutainers - disposable tubes specially adapted for taking such blood samples.

The total iron binding capacity of serum reflects the degree of serum starvation and transferrin saturation with iron. Normally, the total iron-binding capacity of serum is 30 - 85 µmol/l; with iron deficiency, the value increases.

The difference between the total iron-binding capacity of serum and serum iron characterizes the latent iron-binding capacity of serum. The latter two tests are rarely used to diagnose iron deficiency anemia. The ratio of serum iron to the total iron-binding capacity of serum, expressed as a percentage, reflects the degree of saturation of transferrin with iron (normal - 16% - 50%). Iron deficiency anemia is characterized by an increase in the total iron-binding capacity of blood serum, a significant increase in latent iron-binding capacity and a decrease in the percentage of transferrin saturation.

Decreased serum ferritin levels are the most sensitive and specific laboratory sign of iron deficiency; Normal ferritin content is 15 - 20 μg/l.

Desferal test - normally, after intravenous administration of 500 mg of desferal, 0.8 to 1.2 mg of iron is excreted in the urine, while in patients with iron deficiency, the amount of this microelement excreted in the urine is 0.2 mg or less. At the same time, if there is an excess iron content, its excretion in the urine after the administration of desferal exceeds the norm. This test is rarely used, more often for diagnosing hemosiderosis rather than sideropenia.

Determination of serum transferrin levels allows one to exclude anemia caused by impaired iron transport (atransferrinemia).

Glycoprotein transferrin is a protein involved in the transport of iron from the site of its absorption (small intestine) to the site of its use or storage (bone marrow, liver, spleen). One transferrin molecule can bind a maximum of two iron atoms. With a lack of iron absorption, transferrin saturation becomes incomplete, i.e., the percentage of saturation decreases, which indicates anemia caused by a lack of iron intake. However, such a model is valid only in the ideal case. In reality, it is necessary to take into account that transferrin is characterized by the qualities of a “negative” protein of the acute phase, i.e. acute inflammation helps to reduce the level of transferrin. In addition, the formation of transferrin largely depends on the condition of the liver. On the other hand, iron deficiency affects transferrin levels through induction, i.e. ultimately causes an increase in its production. All of these factors can influence transferrin levels to such an extent that their initial diagnostic value may ultimately be ambiguous. Normally, transferrin levels range from 2.0 to 3.8 g/l.

Transport of iron into the cell occurs through the interaction of the iron-transferrin complex with a transferrin-specific receptor on the plasma membrane. The transferrin molecule, carrying up to two iron atoms, “moored” to the outer (extracellular) end of the receptor, after which it was absorbed by the cell by endocytosis. In the formed vesicle, the pH level changes, iron changes its oxidation state (from Fe +++ to Fe ++) and is subsequently used for the synthesis of hemoglobin or stored in the form of deposited iron. The protein part of transferrin, freed from iron, together with the receptor comes to the cell surface, where apotransferrin is separated, and the whole cycle is repeated. Normally, the level of transferrin receptors ranges from 8.8 to 28.1 nmol/l.

A schematic change in iron metabolism indicators depending on the degree of its deficiency is shown in Table B.1 (Appendix B).

To prevent mistakes, the doctor, when determining the pathogenetic variant of anemia, should be guided by the following provisions: do not prescribe treatment with iron supplements until the level of serum iron and the number of reticulocytes are determined; if the patient does not receive iron supplements for long, they are discontinued for 5 to 7 days, after which the iron content in the serum is determined.

To search for the disease underlying iron deficiency in a given patient, use additional methods instrumental and laboratory examination (x-ray and endoscopic examination of the gastrointestinal tract; ultrasonography organs abdominal cavity, pelvis, kidneys). In the process of diagnosing the disease, blood loss from the gastrointestinal tract is assessed, most reliably using one’s own red blood cells labeled with radioactive chromium. Finding the source of bleeding in the small intestine may require laparotomy; an alternative to this may be a special automated video camera in a video capsule swallowed by the patient.

Determination of the cause of iron deficiency is carried out according to protocols for the management of patients with relevant diseases.

Features of diagnosis in patients with iron deficiency anemia in some age groups and under various conditions are characterized by the following. Patients with newly identified symptoms -

Appendix 1. Questionnaire EQ-5D Appendix 2. Patient card Appendix 3. Bibliography for the protocol for the management of patients “Iron deficiency anemia” Appendix 4. Formal entries for the protocol for the management of patients “Iron deficiency anemia”

Patient management protocol.
Iron-deficiency anemia
(approved by the Ministry of Health and Social Development of the Russian Federation on October 22, 2004)

I. Scope of application

The “Iron Deficiency Anemia” patient management protocol is intended for use in the healthcare system of the Russian Federation.

Treatment errors

The patient and his family (relatives) were not adequately trained in the rules of drug therapy.

Iron supplements are prescribed in inadequate (small) doses.

Treatment is short-term; adequate patient adherence to therapy is not achieved.

Vitamins, biologically active supplements or medications with low iron content are prescribed unreasonably.

Treatment of iron deficiency anemia in certain age groups and conditions

Iron deficiency anemia in children of puberty (juvenile chlorosis). Iron deficiency during the period of rapid growth is a consequence of a reduced iron supply that is not compensated for in the first years of life. An abrupt increase in iron consumption by a rapidly growing organism and the appearance of menstrual blood loss aggravate the relative deficiency. Therefore, during puberty, it is advisable to use dietary prevention of iron deficiency, and if signs of hyposiderosis appear, prescribe iron supplements.

Iron deficiency anemia in menstruating women. Simply calculating the approximate amount of iron lost through menstrual blood can help determine the source of blood loss. On average, a woman loses about 50 ml of blood (25 mg of iron) during menstruation, which determines twice the loss of iron compared to men (if distributed over all days of the month, then an additional 1 mg per day). At the same time, it is known that in women suffering from menorrhagia, the amount of blood lost reaches 200 ml or more (100 mg of iron or more), and, therefore, the additional average daily loss of iron is 4 mg or more. In such situations, the loss of iron in 1 month exceeds its possible intake from food by 30 mg, and in one year the deficiency reaches 360 mg.

The rate of progression of anemia during uterine blood loss, in addition to the severity of menorrhagia, is influenced by the initial value of iron reserves, dietary habits, previous pregnancies and lactation, etc. To estimate the volume of blood lost during menstruation, it is necessary to clarify the number of pads a woman changes daily and their characteristics (lately pads with different absorbent properties have been used, a woman chooses her pads depending on the volume of blood loss), the presence of a large number of large clots. Relatively small, “normal” blood loss is considered to be the use of 2 pads per day, the presence of small (1 - 2 mm in diameter) and a small number of clots.

In cases where the cause of iron deficiency is menstrual blood loss, a single course of replacement therapy is not sufficient, since a relapse will occur after a few months. Therefore, maintenance preventive therapy is carried out, usually individually selecting the dose of the drug using titration. It is recommended to take iron-containing preparations with a high iron content from the first day of menstruation for 7 to 10 days. For some women, it is enough to carry out such maintenance therapy once every quarter or every six months. A consensus must be reached between the doctor and the patient about the essence of anemia, methods of therapy, and the importance of prevention. All this significantly increases treatment compliance.

Iron deficiency anemia in women during pregnancy and lactation. To prevent anemia in this group of patients, combination drugs with a relatively low iron content (30 - 50 mg), including vitamins, including folic acid and vitamin B_12, are often used. This type of prophylaxis has been shown to have no effect (level of evidence A). Pregnant women with identified iron deficiency anemia are prescribed medications containing large amounts of iron (100 mg, 2 times a day) for the entire remaining period of pregnancy; during lactation (in the absence of large blood loss during childbirth and menstrual losses and with full compensation of anemia), you can switch to medications with a lower iron content (50 - 100 mg per day). If there is no effect from the therapy, first of all, the adequacy of the prescribed doses (possibly they should be increased) and the correctness of the woman’s fulfillment of the prescribed prescriptions (compliance) are analyzed. In addition, there may be “false anemia” as a consequence of hydremia (blood dilution), often observed in pregnant women (to confirm, it is necessary to examine the volume of circulating blood, evaluate the ratio of the volume of circulating plasma to the volume of circulating erythrocytes, hypochromia of erythrocytes and serum iron content). Anemia is also observed with nephropathy (preeclampsia), with chronic infections (usually urinary tract); in case of persistent anemia, especially in combination with low-grade fever, lymphadenopathy, and causeless sweating, it is necessary to exclude the presence of tuberculosis. In these cases we are talking about anemia of chronic diseases. There are no direct contraindications for the use of parenteral iron supplements in pregnant women, but large-scale studies have not been performed in this group.

Iron deficiency anemia in old age. The main anemias in this group of patients are iron deficiency and B_12 deficiency. No specific treatment regimens for anemia are required, and patients usually respond quickly to prescribed therapy. The ineffectiveness of therapy for iron deficiency anemia is often associated with constipation caused by dysbacteriosis and peristalsis disorders. In such cases, lactulose can be added to therapy in an adequate dose of up to 50 - 100 ml; after obtaining a lasting effect, the dose of lactulose is halved.

VII. Characteristics of requirements

7.1. Patient model

Nosological form: iron deficiency anemia

Stage: any

Phase: any

Complication: regardless of complications

7.1.1. Criteria and signs defining the patient model

A combination of all the following is required:

Decrease in hemoglobin level below 120 g/l;

A decrease in the level of red blood cells below 4.2 x 10(12)/l;

Hypochromia of erythrocytes;

A decrease in one of the indicators of saturation of erythrocytes with hemoglobin (color index (CI) below 0.85, average corpuscular hemoglobin content (MCH) below 24 pg, average hemoglobin concentration in erythrocytes (MCHC) below 30 - 38 g/dl);

A decrease in serum iron levels below 13 µmol/L in men and below 12 µmol/L in women.

7.1.2. Procedure for including a patient in the protocol

The patient is included in the protocol if the patient’s condition (history, clinical and laboratory data) meets the criteria and characteristics that define the patient model.

7.1.3. Requirements for outpatient diagnostics

	Name	Multiplicity of execution
	Study of the level of red blood cells in the blood
	Study of the level of leukocytes in the blood
	Study of platelet levels in the blood
	Ratio of leukocytes in the blood (blood formula)
	View a blood smear to analyze abnormal morphology of red blood cells, platelets, and white blood cells
	Taking blood from a finger
	Determination of the average content and average concentration of hemoglobin in erythrocytes	As needed
	Cytological examination of a bone marrow smear (bone marrow formula calculation)	As needed
	Histological examination of bone marrow preparations	As needed
	Hematocrit estimation	As needed
		As needed
		As needed
	Obtaining a cytological preparation of bone marrow by puncture	As needed
	Obtaining a histological specimen of bone marrow	As needed
		As needed
	Study of osmotic resistance of erythrocytes	As needed
	Study of acid resistance of erythrocytes	As needed
		As needed
	Desferal test	As needed
	Determination of the volume of blood loss through the gastrointestinal tract using radioactive chromium	As needed

7.1.4. Characteristics of algorithms and features of non-drug care

Diagnosis of iron deficiency anemia:

Stage 1: determination (confirmation) of the iron deficiency nature of anemia;

Stage 2: Determining the cause of iron deficiency.

Determination of iron deficiency anemia

Collection of anamnesis and complaints for diseases of the hematopoietic and blood organs

Identifying signs of sideropenia. Clarification of the diet (exclusion of vegetarianism and other diets with a reduced content of iron-containing foods); the possible source of blood loss or increased iron consumption is clarified.

Objective examination for diseases of the hematopoietic and blood organs

Aimed at identifying signs in the patient that characterize hyposiderosis and identifying diseases (conditions) with increased iron consumption.

Study of the level of erythrocytes, leukocytes, platelets, reticulocytes color index. The ratio of leukocytes in the blood (blood formula). Study of the level of total hemoglobin.

The analysis is aimed at identifying signs of blood diseases that may be accompanied by anemia (see stage 2 of the diagnostic search). A decrease in color index is decisive in making a diagnosis of iron deficiency anemia. The results of all studies are analyzed by the doctor together; no single symptom is specific for iron deficiency.

View a blood smear to analyze abnormal morphology of red blood cells, platelets, and white blood cells. The most accurate method for determining the hemoglobin content in erythrocytes remains a morphological study of erythrocytes. In iron deficiency anemia, a distinct hypochromia is detected, characterized by the presence of a wide clearing in the center of the erythrocyte, which resembles a donut or ring (anulocyte).

Serum iron test

It is a mandatory diagnostic test for diagnosing iron deficiency anemia. It is necessary to pay attention to the reasons for false-positive results: failure to comply with the technology of the study; the study is carried out soon after taking (even a single dose) iron supplements; after hemo- and plasma transfusion.

Methodology used in automatic analyzers.

Study of transferrin and serum ferritin levels

Necessary studies in case of doubt about the form of anemia. Research is carried out as part of a complex of iron metabolism studies. Determination of serum transferrin levels allows one to exclude anemia caused by impaired iron transport (atransferrinemia).

Ferritin level test

A decrease in serum ferritin levels is the most sensitive and specific laboratory sign of iron deficiency.

Iron binding capacity of serum

The total iron-binding capacity of serum reflects the degree of serum starvation and transferrin saturation with iron. Iron deficiency anemia is characterized by an increase in the total iron-binding capacity of serum.

Determination of sideroblasts and siderocytes

Counting sideroblasts (erythroid cells of the bone marrow with iron granules) allows us to confirm the iron deficiency nature of anemia (their number in patients with iron deficiency anemia is significantly reduced). The study is rarely performed, only in complex differential diagnostic cases.

Study of osmotic and acid resistance of erythrocytes

The study of osmotic and acid resistance of erythrocytes is carried out for differential diagnosis with erythrocyte membranopathies.

Determining the Cause of Iron Deficiency

Stage 2 - determining the cause of iron deficiency is carried out in accordance with the requirements stipulated by other protocols for the management of patients (gastric ulcer, uterine leiomyoma, etc.). In particular, with the help of erythrocytes labeled with radioactive chromium, the fact of blood loss through the gastrointestinal tract is confirmed.

If necessary, cytological and histological examinations of a bone marrow smear, a study of the acid resistance of erythrocytes, and a desferal test are carried out.

7.1.5. Requirements for outpatient treatment

	Name	Multiplicity of execution
	Collection of anamnesis and complaints for diseases of the hematopoietic and blood organs
	Visual examination for diseases of the hematopoietic and blood organs
	Study of the level of reticulocytes in the blood
	Determination of color index
	Study of the level of total hemoglobin in the blood
	Taking blood from a finger
	Palpation for diseases of the hematopoietic and blood organs	As needed
	Percussion for diseases of the hematopoietic and blood organs	As needed
	General therapeutic auscultation	As needed
	Determination of the average hemoglobin content in erythrocytes	needs
	Hematocrit estimation	needs
	Serum iron level test	As needed
	Testing ferritin levels in the blood	As needed
	Study of serum transferrin level	As needed
	Taking blood from a peripheral vein	As needed
	Study of iron-binding ability of serum	As needed

7.1.6. Characteristics of algorithms and features of non-drug care

Collection of anamnesis and complaints for diseases of the hematopoietic and blood organs, physical examination

Collection of complaints and physical examination are carried out twice to assess the dynamics in the general condition (well-being) of patients.

“Small signs” of effectiveness are very important from the point of view of early assessment of the effectiveness of therapy.

Blood reticulocyte level test

The first objective effect of the drug should be a reticulocyte crisis, manifested by a significant - 2-10 times increase in the number of reticulocytes compared to the initial value by the end of the first week of therapy. The absence of a reticulocyte crisis indicates either an erroneous prescription of the drug or the prescription of an inappropriately small dose.

Study of the level of red blood cells, total hemoglobin

An increase in hemoglobin levels and the number of red blood cells is usually observed in the 3rd week of therapy, later hypochromia and microcytosis disappear. By the 21st - 22nd day of treatment, hemoglobin usually normalizes (with adequate doses), but the depot does not become saturated.

If necessary, determine the level of the color index, the average hemoglobin content in erythrocytes, study the serum iron level, ferritin level, serum transferrin, assess the hematocrit and iron-binding capacity of the serum.

Depot saturation can only be checked using a comprehensive biochemical study. Thus, monitoring the effectiveness of therapy is an essential component of the rational use of iron-containing drugs.

7.1.7. Requirements for medication assistance

7.1.8. Characteristics of algorithms and features of the use of medications

Replacement therapy Iron deficiency is treated with iron supplements. Currently, two groups of iron preparations are used - containing divalent and trivalent iron, in the vast majority of cases used orally.

One of the drugs is used: iron sulfate (orally), iron (III) hydroxide sucrose complex (intravenously), iron (III) hydroxide polymaltose complex (orally and parenterally).

Some drugs are available in the form of syrups and suspensions, which makes them easier to administer to children. However, here too, the recalculation of the daily dose should be made taking into account the iron content per unit volume.

For better tolerance, iron supplements are taken with meals. It is necessary to take into account that under the influence of certain substances contained in food (tea tannin, phosphoric acid, phytin, calcium salts, milk), as well as with the simultaneous use of a number of medications (tetracycline drugs, Almagel, phospholugel, calcium preparations, chloramphenicol, penicillamine, etc. ) absorption of iron from iron salt preparations may be reduced. These substances do not affect the absorption of iron from iron III hydroxide palimaltose complex.

Prescribing iron supplements without recalculating the daily dose is ineffective and leads to the development of false “refractoriness” ().

Iron supplements are prescribed for 3 weeks; after the effect is obtained, the dose of the drug is reduced by 2 times and prescribed for another 3 weeks.

Iron sulfate: the optimal daily dose for iron preparations should correspond to the required daily dose of ferrous iron, which is for children under 3 years old 5 - 8 mg/kg per day, over 3 years old - 100 - 120 mg/day, adults - 200 mg/day. (100 mg 2 times a day 1 hour before or 2 hours after meals). Duration of treatment - 3 weeks, after which - maintenance therapy (1/2 dose) for at least 3 weeks ().

Iron (III) hydroxide polymaltose complex is a new group of iron preparations containing ferric iron as part of a polymaltose complex. They have no less pronounced effect in terms of the speed of saturation of the body with iron than divalent iron. Ferric iron preparations are practically free of side effects. Used in the form of a solution for intramuscular administration, solution and tablets in accordance with the requirements of formulary articles for drugs.

Iron (III) hydroxide sucrose complex - for parenteral administration, administer 2.5 ml on the 1st day, 5 ml on the 2nd and 10 ml on the 3rd days, then 10 ml 2 times a week. The dose of the drug is calculated taking into account the degree of anemia, body weight and iron reserves.

Parenteral administration of iron supplements should be used only in the following exceptional cases:

In the presence of severe intestinal pathology with malabsorption (severe enteritis, malabsorption syndrome, resection of the small intestine, etc.);

Absolute intolerance to iron preparations when taken orally (nausea, vomiting), which does not allow further treatment to be continued. Currently rare due to the emergence of new generations of drugs:

The need to quickly saturate the body with iron when surgical interventions are planned for patients with iron deficiency anemia;

Some authors believe that for patients with exacerbation of gastric or duodenal ulcers, Crohn's disease, or nonspecific ulcerative colitis, oral iron supplementation is undesirable. However modern drugs are free from this limitation:

When treating patients with erythronoetin.

Treatment of iron deficiency anemia in children

It is necessary that the child receives at least 6 mg of iron per day (normal daily requirement); if there is a deficiency, this amount must be increased by 5 to 10 times.

To compensate for iron deficiency, you can use special milk formulas enriched with iron, but be sure to add iron-containing syrups or solutions, having previously calculated the required volume. In addition, a mother who has a proven iron deficiency, even in the absence of anemia, should receive iron supplements both during pregnancy and lactation, which will be in the first case a factor in the prevention of iron deficiency in the newborn, in the second - an additional factor in therapy.

Treatment of iron deficiency anemia in pregnant women

There is no evidence that giving iron supplements to all women without a diagnosis of iron deficiency in the second half of pregnancy and throughout lactation prevents the occurrence of iron deficiency in the fetus (level of evidence A).

Treatment of iron deficiency in pregnant and lactating women is carried out according to the general scheme with the prescription of drugs containing high doses of iron.

Treatment of iron deficiency anemia in the elderly

No specific treatment regimens for anemia are required, and patients usually respond quickly to prescribed therapy. The ineffectiveness of therapy for iron deficiency anemia is often associated with constipation caused by dysbacteriosis and peristalsis disorders. In such cases, an adequate dose of lactulose is added to therapy in a dose of 50-100 ml; after obtaining a lasting effect, the dose of lactulose is halved (level of evidence C).

When selecting therapy for elderly patients suffering from iron deficiency anemia, it is necessary:

Choose a drug with good oral bioavailability and no side effects that aggravate both the subjective condition of the patient and impair absorption (for example, by pores);

Choose a drug with a therapeutic focus on only one pathogenetic variant of anemia (prevention of errors during therapy).

Treatment of iron deficiency anemia with insufficient kidney function

If renal function is impaired, dose adjustment of iron-containing drugs is not required. Treatment of iron deficiency conditions is carried out mainly with oral medications. In case of iron deficiency and the use of erythropoietin, parenteral (intravenous) administration of iron-containing drugs is permissible immediately before the administration of a dose of erythropoietin ().

7.1.9. Requirements for work, rest, treatment or rehabilitation regimes

There are no special requirements for the regime of work, rest, treatment, or rehabilitation; during periods of severe exacerbation of the disease, elderly people should refrain from heavy physical activity, which could potentially cause palpitations (level of evidence C).

7.1.10. Requirements for patient care and ancillary procedures.

There are no special requirements.

7.1.11. Requirements for dietary prescriptions and restrictions#

Dietary prescriptions do not play a significant role in the treatment of iron deficiency anemia. The exception is the elderly, adherents of vegetarianism and other diets with a low content of iron-containing foods, who should be advised to expand the diet to include meat products.

7.1.12. Informed voluntary consent of the patient when performing the protocol

The patient gives informed voluntary consent in writing.

7.1.13. Additional information for the patient and his family members

Pregnant women, women breastfeeding, and elderly patients should be advised of the need to follow a diet rich in iron.

7.1.14. Rules for changing requirements when executing the protocol and terminating protocol requirements

If signs of another disease requiring diagnostic and therapeutic measures are detected, in the absence of this disease, the patient is transferred to the Protocol for the management of patients with the corresponding (identified) disease or syndrome.

If signs of another disease requiring diagnostic and therapeutic measures are identified, along with signs of this disease (identifying sources of blood loss), medical care is provided to the patient in accordance with the requirements:

a) the section of this Patient Management Protocol relevant to the treatment of iron deficiency anemia;

b) Protocol for the management of patients with an identified disease (syndrome).

If the patient has a mental, neurological or other disease, as a result of which the patient, in the absence of a person caring for him, cannot independently fully fulfill all the necessary prescriptions, when iron deficiency anemia is combined with other diseases in the acute stage, requiring inpatient care, treatment is carried out in inpatient conditions in accordance with the requirements of a given patient model.

7.1.15. Possible outcomes and their characteristics

Outcome name	Frequency of development, %	Criteria and signs	Estimated time to reach outcome	Continuity and phasing of medical care
Remission		Normalization of total hemoglobin levels	21 days from the start of therapy	Maintenance therapy according to the algorithm
Improvement		Elimination of clinical symptoms; a clear increase in the level of total hemoglobin up to 110 g/l and above, but without its normalization;	21 days from the start of therapy	Continuation of treatment according to the algorithm
No effect		The appearance of clinical or laboratory signs of non-iron deficiency anemia, lack of increase in hemoglobin	14 - 30 days	Providing assistance according to the protocol of the corresponding disease 3rd week	4 - 6th week
	Assessment of subjective sensations	Reticulocyte crisis	Increase in hemoglobin and number of red blood cells	Disappearance of hypochromia, normalization of hemoglobin levels

Some characteristics of tablet forms of iron-containing preparations

Commercial name		Composition, release form		Special indications
Aktiferrin	Ferrous sulfate + series	Pills
Hemophere prolongatum	Ferrous sulfate
Maltofer Fall	Iron polymaltosate + folic acid	Chewable tablets 100 mg/0.35 mg	100 mg Fe(+++)	Pregnant and lactating women
Maltofer	Iron polymaltosate	Chewable tablets 100 mg	100 mg Fe(+++)	Pregnant and lactating women
Sorbifer-Durules		Tablets 320/60 mg
Tardiferon	Iron sulfate + mucoproteosis + ascorbic acid	Pills
	Iron sulfate + ascorbic acid + riboflavin + nicotinamide + pyridoxine + calcium pantathenate	Pills		Pregnant and lactating women
Ferretab	Iron fumarate
Ferroplex	Iron sulfate + ascorbic acid	Tablets 50 mg/30 mg		Children and teenagers
	Iron fumarate	Capsules 350 mg

Some characteristics of syrups and other liquid forms of iron-containing preparations

Commercial name	International nonproprietary name	Composition, release form
Aktiferrin	Ferrous sulfate + series	Drops 30 ml	1 ml 9.8 mg
Aktiferrin	Ferrous sulfate + series	Syrup 100 ml	1 ml 6.8 mg
	Ferric chloride	Drops (bottles) 10 and 30 ml	1 ml 44 mg
	Iron gluconate, manganese gluconate, copper gluconate	Mixture for preparing a solution in ampoules	1 ampoule 50 mg
Maltofer	Iron polymaltosate	Solution for internal use (drops) 30 ml	In 1 ml 50 mg Fe(+++)
Maltofer	Iron polymaltosate	Syrup 150 ml	In 1 ml 10 mg Fe(+++)
Ferrum Lek	Iron polymaltosate	Syrup, 100 ml	In 1 ml 10 mg Fe(+++)

Commercial name	International nonproprietary name	Composition, release form
	Iron III hydroxide sucrose complex	Solution for intravenous injection 100 mg - 5 ml 20 mg - 1 ml
Maltofer	Iron polymaltosate	R\r for intramuscular injections 100 mg - 2 ml
Ferrum Lek	Iron polyisomaltosate	Solution for intramuscular injection, 100 mg - 2 ml

IX. Monitoring

Criteria and methodology for monitoring and evaluating the effectiveness of the protocol implementation

Monitoring is carried out throughout the Russian Federation.

The institution responsible for monitoring this protocol is the Moscow medical Academy them. THEM. Sechenov Ministry of Health of Russia. The list of medical institutions in which monitoring of this protocol is carried out is determined by the Ministry of Health and Social Development of the Russian Federation. Medical institutions are informed about inclusion in the list of monitoring protocols in writing.

Protocol monitoring includes:

Collection of information on the management of patients with iron deficiency anemia in medical institutions of all levels;

Analysis of the obtained data;

Drawing up a report on the results of the analysis;

Submission of the report to the Ministry of Health and Social Development of the Russian Federation.

The initial data for monitoring are:

Medical documentation - patient cards (see Appendix 2 to this protocol for patient management);

Tariffs for medical services;

Prices for medicines.

If necessary, when monitoring the protocol, medical histories, outpatient records of patients suffering from iron deficiency anemia, and other documents can be used.

Patient cards (see Appendix 2 to this patient management protocol) are filled out in medical institutions, determined by the monitoring list, quarterly for consecutive 10 days of the third ten-day period of each first month of the quarter (for example, from January 21 to January 30), and are transferred to the institution responsible for monitoring no later than 2 weeks after the end of the specified period.

The selection of maps included in the analysis is carried out using a random sampling method. The number of cards analyzed must be at least 500 per year.

The indicators analyzed during the monitoring process include: criteria for inclusion and exclusion from the Protocol, lists of medical services of the mandatory and additional range, lists of medicines of the mandatory and additional range, disease outcomes, cost of medical care under the Protocol, etc.

Principles of randomization

This Protocol does not provide for randomization (of medical institutions, patients, etc.).

Procedure for assessing and documenting side effects and complications

Information about side effects and complications that arose during the diagnosis of patients is recorded in the Patient Card (see Appendix 2

The procedure for including and excluding a patient from monitoring

The patient is considered included in the monitoring when he fills out the “Patient Card” (see Appendix 2 to this protocol for patient management). Exclusion from monitoring is carried out if it is impossible to continue filling out the Card (for example, failure to show up for a medical appointment, etc.).

In this case, the Card is sent to the institution responsible for monitoring, with a note indicating the reason for excluding the patient from the protocol.

Interim evaluation and protocol changes

Evaluation of protocol implementation is carried out once a year based on the results of analysis of information obtained during monitoring.

Amendments to the Protocol are carried out if information is received about the emergence of convincing data on the need for changes to the mandatory level requirements of the Protocol.

The decision on changes and their implementation are carried out by the Ministry of Health and Social Development of the Russian Federation.

Parameters for assessing quality of life when performing the protocol

The assessment of the quality of life of a patient with iron deficiency anemia during the implementation of the protocol is carried out using the European Quality of Life Questionnaire (see Appendix 1 to this patient management protocol).

Estimation of the cost of implementing the protocol and the price of quality

Clinical and economic analysis is carried out in accordance with the requirements of regulatory documents. The questionnaire is filled out twice: 1st time in its entirety before starting therapy, the second time - five questions and a mark is placed on the thermometer (visual analogue scale).

Comparison of results

When monitoring the protocol, the results of fulfilling the requirements of the protocol, statistical data (morbidity), and performance indicators of medical institutions are annually compared.

Report generation procedure

The annual report on monitoring results includes quantitative results obtained during the development of medical records, and their qualitative analysis, conclusions, and proposals for updating the protocol.

The report is submitted to the Ministry of Health and Social Development of the Russian Federation by the institution responsible for monitoring this protocol. The results of the report may be published publicly.

Deputy Minister health care and open this document right now or request it via the Hotline in the system.

For quotation: Dvoretsky L.I. Algorithms for the diagnosis and treatment of anemia // RMZh. 2003. No. 8. P. 427

MMA named after I.M. Sechenov

Sh a wide range of different diseases leading to anemia along with various mechanisms development of anemic syndrome allows us to consider it appropriate to carry out a diagnostic search in a certain sequence with the solution of a specific diagnostic problem at each stage of the search.

At the initial stage of the diagnostic search, the main goal is to determine the so-called pathogenetic variant of anemia (AN), i.e. the main mechanism causing the decrease in hemoglobin levels in a particular patient.

Based on the predominant mechanism (not the cause!) of formation various types Anemia can be divided into several pathogenetic variants:

- iron deficiency AN

Sideroachrestic (iron-saturated) AN

Iron redistribution AN

B 12 - deficient and folate-deficient AN

Hemolytic AN

Anemia in bone marrow failure

Anemia with a decrease in circulating blood volume

Anemia with a mixed mechanism of development.

At this stage, we are actually talking about syndromic diagnosis, since each of the pathogenetic variants represents only a separate anemic syndrome (iron deficiency syndrome, hemolytic anemia syndrome, etc.). These options reflect only the leading pathogenetic mechanism, while the reasons for the development of AN for each pathogenetic option may be different. For example, the cause of iron deficiency anemia can be chronic blood loss from the gastrointestinal tract, intestinal pathology with malabsorption, nutritional deficiency, etc. Sideroachrestic anemia can develop in patients with chronic lead intoxication, during treatment with certain medications (isoniazid, etc.).

At the next stage of the diagnostic search, after determining the pathogenetic variant of anemia, the doctor’s task is to recognize the disease or pathological process, underlying the existing anemic syndrome, i.e. identifying the cause of anemia in a particular patient. This stage of the diagnostic search can be conventionally designated as nosological diagnosis. The latter becomes important because in many cases it allows not only pathogenetic therapy of anemia, for example, with iron supplements, but also to influence the underlying disease (elimination of chronic blood loss in iron deficiency anemia, relief of the infectious-inflammatory process, etc.).

Iron deficiency anemia

The main pathogenetic mechanism for the development of iron deficiency anemia (IDA) is a lack of iron in the body - the main building material for the construction of the hemoglobin molecule, in particular, its iron-containing part - heme. The main criteria for IDA are the following:

Low color index

Hypochromia of erythrocytes, microcytosis

Decreased serum iron levels

Increasing the total iron-binding capacity of serum

Decreased serum ferritin levels.

At the stage of nosological diagnosis, the search for the cause of IDA should be carried out using the most informative research methods for a specific clinical situation (history data, objective examination, additional methods, etc.) (Fig. 1).

Rice. 1. Diagnostic search algorithm for hypochromic and normo-/hyperchromic anemia

The main reasons for the development of IDA:

1. Chronic blood loss of various locations:

1. Chronic blood loss of various locations:

Gastrointestinal (gastroesophageal reflux disease, erosive and ulcerative lesions of the stomach, tumors of the stomach and colon, terminal ileitis, ulcerative colitis, diverticulitis, bleeding hemorrhoids, etc.);

Uterine (menorrhagia of various etiologies, fibroids, endometriosis, intrauterine contraceptives;

Nasal (hereditary hemorrhagic telangiectasia and other hemorrhagic diathesis);

Renal (IgA nephropathy, hemorrhagic nephritis, kidney tumors, permanent intravascular hemolysis);

Iatrogenic and artificial blood loss (frequent bloodletting and blood sampling for research, hemodialysis treatment, donation, etc.).

2. Impaired absorption of iron (enteritis of various origins, malabsorption syndrome, resection small intestine, gastric resection with exclusion of the duodenum).

3. Increased need for iron (pregnancy, lactation, intensive growth and puberty, B 12 deficiency anemia treated with cyanocobalamin).

4. Impaired iron transport (hypoproteinemia of various origins).

5. Nutritional deficiency.

Treatment . When identifying the cause of the development of IDA, the main treatment should be aimed at eliminating it ( surgical treatment tumors of the stomach, intestines, treatment of enteritis, correction of nutritional deficiency, etc.). In a number of cases (menorrhagia, etc.), pathogenetic therapy with iron (iron) drugs becomes of primary importance.

In clinical practice, pancreas is used orally or parenterally. The route of administration of the drug in patients with IDA is determined by the specific clinical situation. In most cases, to correct iron deficiency in the absence of special indications, pancreas should be administered orally. The Russian pharmaceutical market has a wide selection of PZ for oral administration. They differ in the amount of iron salts they contain, including divalent iron, the presence of additional components (ascorbic and succinic acid, vitamins, fructose, etc.), dosage forms (tablets, dragees, syrups, solutions), tolerability, cost (Table 1)

Clinical recommendations for the treatment of pancreas for oral administration:

Prescription of pancreas in the form of salts orally with a sufficient content of ferrous iron;

Prescription of pancreas in the form of salts orally with a sufficient content of ferrous iron;

Prescription of pancreas containing substances that enhance iron absorption;

It is undesirable to simultaneously take nutrients and medications that reduce iron absorption;

The advisability of prescribing iron supplements containing folic acid, cyanocobalamin in the presence of mixed anemia;

Prescribing iron supplements parenterally in case of impaired intestinal absorption;

Sufficient duration of the saturating course of therapy (at least 1-1.5 months);

The need for maintenance therapy of the pancreas in appropriate situations.

When choosing a medicinal pancreas, you should focus on the content of divalent iron in it, which is only absorbed in the intestine. Included in many dosage forms Pancreatic ascorbic acid, cysteine, fructose enhance iron absorption. Prescribing iron supplements in high doses (300 mg per day) does not increase the absorption of iron ions, but causes a significant increase in the number of side effects. Taking this into account, combination preparations containing folic acid, as a necessary component for the normal synthesis and maturation of red blood cells, and cyanocobalamin, necessary for the normal metabolism of folic acid, which is the main factor in the formation of its active form, lead to a significant increase in the rate of hemoglobin synthesis and increase the effectiveness of therapy for iron deficiency anemia. A complex antianemic drug satisfies all these criteria. Ferro foil , containing in its composition, in addition to ferrous sulfate, 100 mg of ascorbic acid, 10 mcg of cyanocobalamin, 5 mg of folic acid. So, for example, when prescribing a drug with a low content of ferrous iron, the number of tablets taken should be at least 8-10 per day, while drugs with a high content of ferrous iron (Ferro-foil) can be taken in the amount of 1-2 tablets per day . It must be taken into account that the absorption of iron may be reduced under the influence of certain substances contained in food (phosphoric acid, calcium salts, etc.), as well as with the simultaneous use of a number of medications (tetracyclines, magnesium salts). To avoid this, in Ferro-Folgamma all active components are contained in a special neutral shell, which ensures their absorption mainly in the upper part of the small intestine. The absence of local irritation on the gastric mucosa contributes to good tolerability.

Among the side effects associated with the use of pancreatic acid orally, the most common are nausea, anorexia, metallic taste in the mouth, constipation, and less commonly, diarrhea.

Indications for the use of parenteral pancreas may include the following clinical situations:

Malabsorption;

Intolerance of the pancreas for oral administration, which does not allow further continuation of treatment;

The need to more quickly saturate the body with iron, for example, before surgery (uterine fibroids, hemorrhoids, etc.).

The algorithm for managing large IDA is presented in Figure 2.

Rice. 2. Algorithm for the management of patients with iron deficiency anemia

Sideroachrestic anemias

There is a group of hypochromic anemias, in which the iron content in the body and its reserves in the depot are within normal limits or even increased, but the inclusion of iron in the hemoglobin molecule (for various reasons) is impaired, and therefore iron is not used for heme synthesis. Such anemias are designated as sideroachrestic (“achresia” - non-use). Their share in the structure of hypochromic anemia is small. Nevertheless, verification of sideroachrestic (“iron-saturated”) anemia and its differential diagnosis with IDA are of important practical importance. Erroneous diagnosis of IDA in patients with sideroachrestic anemia usually entails unjustified prescription of iron supplements, which in this situation not only have no effect, but further “overload” the iron stores in the depot. The criteria for sideroachrestic anemia are the following:

There is a group of hypochromic anemias, in which the iron content in the body and its reserves in the depot are within normal limits or even increased, but the inclusion of iron in the hemoglobin molecule (for various reasons) is impaired, and therefore iron is not used for heme synthesis. Such anemias are designated as sideroachrestic (“achresia” - non-use). Their share in the structure of hypochromic anemia is small. Nevertheless, verification of sideroachrestic (“iron-saturated”) anemia and its differential diagnosis with IDA are of important practical importance. Erroneous diagnosis of IDA in patients with sideroachrestic anemia usually entails unjustified prescription of iron supplements, which in this situation not only have no effect, but further “overload” the iron stores in the depot. the following:

- low color index;

Hypochromia of erythrocytes;

Increased (less often normal) iron content in serum;

Normal or reduced serum iron-binding capacity;

Normal or elevated serum ferritin levels;

Increased number of sideroblasts in the bone marrow;

Increased urinary iron excretion after administration of Desferal;

Lack of effect from iron supplements.

Sideroachrestic anemias are a heterogeneous group and arise from various causes. Therefore, the nosological stage of the diagnostic search for sideroachrestic anemia should be carried out taking into account both the clinical situation and knowledge of the main diseases and pathological processes accompanied by the development of this anemic syndrome. Several forms of sideroachrestic anemia are known:

Hereditary forms (autosomal and recessive, sensitive and refractory to the use of pyridoxine);

Associated with deficiency of the enzyme heme synthetase (which ensures the inclusion of iron in the heme molecule);

Associated with impaired hemoglobin synthesis due to pathology of its globin part (thalassemia). This disease is usually considered in the group of hemolytic anemias;

Acquired forms (alcohol intoxication, chronic lead intoxication, exposure to certain medications, myeloproliferative diseases, cutaneous porphyria, idiopathic forms).

Correction of the underlying pathological process (withdrawal of a suspected medication, EDTA for lead intoxication, etc.);

Prescription of pyridoxine for certain forms (hereditary);

Prescription of desferrioxyamine for high level serum iron;

Transfusion of red blood cells according to strict indications (severe anemia in patients with concomitant pathologies);

Contraindication to the use of iron supplements.

Iron redistribution anemia

Among hypochromic anemias, anemia with various inflammatory diseases of both infectious and non-infectious origin. With all the diversity of pathogenetic mechanisms of anemia in these situations, one of the main ones is considered to be the redistribution of iron into the cells of the macrophage system, which is activated during various inflammatory (infectious and non-infectious) or tumor processes. Since true iron deficiency is not observed in these anemias, it is more justified to talk about iron redistribution anemias.

Criteria for iron redistribution AN:

• moderately hypochromic anemia;
• normal or moderately reduced serum iron content;
• normal or reduced serum iron-binding capacity;
• increased serum ferritin levels;
• increased number of sideroblasts in the bone marrow;
• clinical and laboratory signs of an active process (inflammatory, tumor);
• lack of effect from iron supplements.

Identification of this pathogenetic variant and awareness of practitioners about it is important due to the similarity of iron redistribution anemias with iron deficiency anemia and some sideroachrestic anemias (Table 2), although the essence and therapeutic approaches for these anemias are different.

The most common infectious and inflammatory diseases in which iron redistribution anemia occurs are active tuberculosis of various localizations, infective endocarditis, suppurative diseases (abscesses of the abdominal cavity, lungs, kidneys, empyema, etc.), urinary tract infections, cholangitis. Among non-infectious diseases, a similar variant of anemia can develop in rheumatic diseases ( rheumatoid arthritis and infectious arthritis with high activity), chronic hepatitis, tumors of various locations in the absence of chronic and acute blood loss. Prescribing iron and cyanocobalamin in these situations is usually ineffective and only delays timely identification of the main cause of anemia and appropriate therapy. The main way to correct anemia in this category of patients is to treat the active inflammatory process.

B 12 - deficiency and folate deficiency anemia

This pathogenetic variant is based on a deficiency of vitamin B12, and less commonly, folic acid, which occurs due to various reasons. As a result of deficiency, DNA synthesis in hematopoietic cells is disrupted, ineffective megaloblastic erythropoiesis develops (normally exists only in the fetus) with the production of unstable megalocytes and macrocytes.

Criteria B 12 - deficient AN:

- high color index;

Macrocytosis, megalocytosis;

Red blood cells with nuclear remains (Jolly bodies, Cabot rings);

Reticulocytopenia;

Hypersegmentation of neutrophils;

Leukopenia (neutropenia);

Thrombocytopenia;

Megaloblastic hematopoiesis in the bone marrow;

Neurological disorders and mental disorders.

At the stage of syndromic diagnosis, the main method is bone marrow examination, which reveals megaloblastic erythropoiesis. This study should be carried out before prescribing cyanocobalamin, which is widely and often unjustifiably prescribed for unclear AN or various neurological symptoms. If it is impossible to perform diagnostic test bone marrow (patient refusal, etc.), a trial administration of cyanocobalamin is permissible, followed by a mandatory study of the number of reticulocytes after 3-5 days (no later), which acquires diagnostic value. If AN is associated with vitamin B12 deficiency, then under the influence of several injections of the drug, megaloblastic hematopoiesis is transformed into normoblastic, which is reflected in the peripheral blood by a significant increase in the number of reticulocytes compared to the initial one (reticulocyte crisis).

The main reasons for the development of B 12 deficiency anemia , the exclusion of which the doctor should focus on at the stage of nosological diagnosis are the following:

Impaired absorption of vitamin B 12 (atrophic gastritis, stomach cancer, gastrectomy surgery, resection of the small intestine, intestinal anastomosis with the formation of a “blind loop”, enteritis with malabsorption, sprue, celiac disease, selective defect (autosomal recessive) absorption in combination with proteinuria , manifested in early childhood(Imerslund syndrome);

Increased need for vitamin B 12 (infestation with tapeworm, colon diverticulosis, intestinal dysbiosis, fast growth in children, hyperthyroidism, chronic diseases liver);

Impaired transport of vitamin B 12 (transcobalamin II deficiency (an autosomal recessively inherited defect that manifests itself in early childhood);

Violation of use when taking certain medications (PASK, neomycin, metformin);

Nutritional deficiency (rare cause) mainly in childhood, with long-term parenteral nutrition without additional vitamins.

Folate-deficient AN in their hematological characteristics (macrocytosis, megaloblastic erythropoiesis) resemble B 12-deficient AN, but are much less common and have a slightly different spectrum of diseases that cause these AN. Among the causes of folate deficiency anemia, the main ones should be considered :

Nutritional deficiency ( common reason in the elderly);

Enteritis with malabsorption;

Taking certain medications that inhibit the synthesis of folic acid (methotrexate, triamterene, anticonvulsants, barbiturates, metformin);

Chronic alcohol intoxication;

Increased need for folic acid (malignant tumors, hemolysis, exfoliative dermatitis, pregnancy).

The algorithm for managing patients with macrocytic anemia of unknown origin is presented in Figure 3.

Rice. 3. Algorithm for the management of patients with macrocytic anemia of unknown cause

Hemolytic anemia

The main pathogenetic mechanism for the development of hemolytic AN (HAN) is a shortening of the lifespan of erythrocytes (normally 100-120 days) and their premature breakdown under the influence of various causes.

The main pathogenetic mechanism for the development of hemolytic AN (HAN) is a shortening of the lifespan of erythrocytes (normally 100-120 days) and their premature breakdown under the influence of various causes.

The GAN criteria are the following:

- normal color index (low in thalassemia);

Reticulocytosis;

The presence of nucleated erythroid cells (erythrokaryocytes) in the blood;

An increase in the number of erythrokaryocytes in the bone marrow (over 25%);

Increased serum indirect bilirubin levels with or without jaundice;

Increased serum iron levels;

The presence of hemosiderin in the urine (in some forms with intravascular hemolysis);

Increased content of free hemoglobin in plasma (with intravascular hemolysis);

Enlarged spleen (in some forms).

Most HANs are normo- or hyperchromic, with the exception of HAN associated with impaired globin synthesis (thalassemia), which is hypochromic.

The direction of the diagnostic search at the nasological stage is determined by the characteristics of the clinical situation (the patient’s age, the presence and nature of the background pathology, medication use, family cases, acute or chronic hemolysis, etc.). It is necessary to distinguish between hereditary and acquired GAN.

Hereditary GANs associated with various genetic defects, in particular, with a defect in the erythrocyte membrane (hereditary microspherocytosis, ovalocytosis), deficiency of certain enzymes in erythrocytes (glucose-6-phosphate dehydrogenase, pyruvate kinase, etc.), impaired synthesis of globin chains (thalassemia), the presence of unstable hemoglobins.

Thalassemia should be suspected in patients with hypochromic anemia with normal or high serum iron levels in combination with signs of hemolysis, as well as in the absence of effect from iron supplements, often mistakenly prescribed to such patients. To confirm the diagnosis and determine the form of thalassemia, an electrophoretic study of hemoglobin is necessary.

Among acquired GAN the most common are autoimmune GANs (symptomatic and idiopathic). Symptomatic autoimmune GANs occur against the background of lymphoproliferative diseases (chronic lymphocytic leukemia, lymphogranulomatosis, etc.), systemic vasculitis (systemic lupus erythematosus, rheumatoid arthritis), chronic active hepatitis, some infections, in particular; viral, when taking a number of medications. If the cause of autoimmune hemolysis is not identified, then they speak of idiopathic GAN. Acquired GANs include Marchiafava disease (permanent intravascular hemolysis), microangiopathic GANs (hemolysis due to disseminated intravascular coagulation due to various diseases), mechanical hemolysis with prosthetic vessels and heart valves, march hemoglobinuria, HAN under the influence of various toxic substances (acetic acid, arsenic, etc.).

The management of patients with autoimmune GAN is determined by the type of GAN (symptomatic or idiopathic). Figure 4 shows an algorithm for the management of patients with autoimmune GAN.

Rice. 4. Treatment algorithm for autoimmune hemolytic anemia

Anemia in bone marrow failure

This pathogenetic variant of AN is based on a disruption of the normal production of erythroid cells in the bone marrow. In this case, often simultaneously with the inhibition of erythropoiesis, there is a disruption in the production of cells of granulocyte and platelet lineages, which affects the composition of the peripheral blood (pancytopenia) and serves as a guide in recognizing the possible mechanism of development of AN.

This pathogenetic variant of AN is based on a disruption of the normal production of erythroid cells in the bone marrow. In this case, often simultaneously with the inhibition of erythropoiesis, there is a disruption in the production of cells of granulocyte and platelet lineages, which affects the composition of the peripheral blood (pancytopenia) and serves as a guide in recognizing the possible mechanism of development of AN.

AN criteria for bone marrow failure:

- normochromic (less often hyperchromic) AN;

Reticulocytopenia (up to the complete absence of reticulocytes in some forms);

Leukopenia due to a decrease in the content of neutrophil granulocytes (granulocytopenia);

Thrombocytopenia varying degrees expressiveness;

Fever, infectious complications, ulcerative necrotic lesions of the mucous membranes;

Hemorrhagic syndrome;

Changes in the pattern of bone marrow hematopoiesis in accordance with the nature of the main pathological process (replacement with adipose tissue, infiltration with blast cells, etc.).

Figure 5 shows a diagnostic algorithm for patients with various types of cytopenic syndrome (pancytopenia, bicytopenia). Figure 6 shows the algorithm for managing patients with aplastic anemia.

Rice. 5. Algorithm for diagnostic search in patients with pancytopenia

Rice. 6. Algorithm for the management of patients with aplastic anemia

Clinical recommendations for the management of patients with aplastic anemia:

• elimination of the identified cause (cancellation medicinal product, thymoma removal, treatment viral infections etc.);
• HLA typing of siblings of patients for the purpose of selecting a bone marrow donor;
• platelet transfusions when the platelet count is below 10x10 9 /l or with less severe thrombocytopenia, but severe hemorrhagic syndrome;
• platelet transfusions from HLA-compatible donors for profuse bleeding;
• transfusion of red blood cells when HB decreases below 70 g/l or with less severe anemia in the elderly and elderly;
• Transfusions of blood components from relatives who are potential bone marrow donors are inappropriate;
• the effectiveness of antithymocyte globulin and cyclosporine is assessed after 3-6 months;
• prescribing glucocorticoids as monotherapy is inappropriate;
• unproven effectiveness of recombinant preparations of germ factors (G-CSF, GM-CSF, IL-1, IL-3);
• providing conditions that prevent infectious complications.

Anemia with combined pathogenetic mechanisms

In clinical practice, AN is often encountered, in the development of which two or more pathogenetic mechanisms may be important. A combined pathogenetic variant can occur in elderly and senile patients (for example, iron deficiency anemia in combination with folate deficiency anemia). In such situations, the prescription of drugs containing iron and folic acid is justified.

Iron deficiency anemia (IDA) is a pathological condition that is characterized by a decrease in hemoglobin content due to iron deficiency in the body when its supply, absorption or pathological losses are impaired.

According to WHO (1973), the lower limit of capillary blood hemoglobin in children under 6 years of age is 110 g/l, and after 6 years - 120 g/l.

Causes of IDA in children:

• Insufficient level of iron in the body (impaired uteroplacental circulation, fetomaternal and fetoplacental bleeding, fetal transfusion syndrome in multiple pregnancies, intrauterine melena, prematurity, multiple births, deep and long-term iron deficiency in the body of a pregnant woman, premature or late ligation of the umbilical cord, intrapartum bleeding due to traumatic obstetric interventions or abnormal development of the placenta and umbilical cord vessels)
• Increased need for iron (premature babies, children with high birth weight, with a lymphatic type of constitution, children in the second half of life).
• Insufficient amount of iron in food (early artificial feeding with cow's or goat's milk, flour, dairy or dairy-vegetarian foods, unbalanced diet that does not contain sufficient dairy products)
• Increased iron losses due to bleeding of various etiologies, impaired intestinal absorption (chronic intestinal diseases, malabsorption syndrome), as well as significant and prolonged hemorrhagic uterine bleeding in girls.
• Disorders of iron metabolism in the body (pre-pubertal hormonal imbalance)
• Disorders of iron transport and utilization (hypo and atransferinemia, enzymopathies, autoimmune processes)
• Insufficient resorption of iron in the digestive tract (post-resection and agastric conditions).

Stages of development of IDA(WHO, 1977)

• prelatent (depletion of tissue iron reserves; blood counts are normal; no clinical manifestations).
• latent (iron deficiency in tissues and a decrease in its transport fund; blood counts are normal; clinical picture caused by trophic disorders that develop as a result of a decrease in the activity of iron-containing enzymes and are manifested by sideropenic syndrome - epithelial changes in the skin, nails, hair, mucous membranes, distortion of taste, smell, disturbances in intestinal absorption and asthenovegetative functions, decreased local immunity).

Iron deficiency anemia (more pronounced depletion of tissue reserves of iron and mechanisms for compensating for its deficiency; deviations from the norm in blood parameters depending on the severity of the process; clinical manifestations in the form of siederopenic syndrome and general anemic symptoms that are caused by anemic hypoxia - tachycardia, muffled heart sounds, systolic murmur, shortness of breath during exercise, pallor of the skin and mucous membranes, arterial hypotension, increased astheno-neurotic disorders).

The severity of anemic hypoxia depends not only on the level of hemoglobin, but also on the speed of development of anemia and on the compensatory capabilities of the body. In severe cases, metabolic intoxication syndrome develops in the form of memory loss, low-grade fever, headache, fatigue, hepatolienal syndrome, etc.
Iron deficiency contributes to decreased immunity and delayed psychomotor and physical development in children.

According to hemoglobin level IDA is divided into degrees of severity:

• light - Hb 110-91 g/l
• average - Hb 90-71 g/l
• heavy -Hb 70-51 g/l
• super heavy -Hb 50 g/l or less

2. Laboratory criteria for diagnosing IDA

• blood test to determine:
• level of hemoglobin, red blood cells
• morphological changes in red blood cells
• color index
• average red blood cell diameter
• average hemoglobin concentration in erythrocytes (MCHC)
• mean erythrocyte volume (MS)
• reticulocyte level
• blood serum analysis to determine:
  • iron and ferritin concentrations
  • total iron-binding capacity of blood
  • latent iron-binding capacity of blood with calculation
  • transferrin saturation coefficient with iron

3. Basic principles of treatment

• Elimination of etiological factors
  • rational therapeutic nutrition (for newborns - natural breastfeeding, and in the absence of mother's milk - adapted milk formulas fortified with iron. Timely introduction of complementary foods, meat, especially veal, offal, buckwheat and oatmeal, fruit and vegetable purees, hard cheeses; reducing the intake of phytates, phosphates, tannin, calcium, which impair the absorption of iron.
• pathogenetic treatment with iron preparations, mainly in the form of drops, syrups, tablets.

Parenteral administration of iron preparations is indicated only: in case of impaired intestinal absorption syndrome and conditions after extensive resection of the small intestine, nonspecific ulcerative colitis, severe chronic enterocolitis and dysbacteriosis, intolerance to oral preparations of glandases, severe anemia.

Preventive measures to prevent relapse of anemia
Correction of iron deficiency in mild anemia is carried out mainly through a balanced diet and sufficient exposure of the child to fresh air. Prescribing iron supplements at a hemoglobin level of 100 g/l and above is not indicated.

Daily therapeutic doses of oral iron supplements for moderate and severe IDA:
up to 3 years - 3 -5 mg/kg/day of elemental iron
from 3 to 7 years - 50-70 mg/day of elemental iron
over 7 years - up to 100 mg/day of elemental iron

Monitoring the effectiveness of the prescribed dose is carried out by determining the rise in reticulocyte levels on the 10-14th day of treatment. Iron therapy is carried out until hemoglobin levels normalize with a further dose reduction by ½. The duration of treatment is 6 months, and for premature babies - for 2 years to replenish iron reserves in the body.

In older children, the maintenance dose lasts for 3-6 months, in girls of puberty - intermittently throughout the year - every week after menstruation.

It is advisable to prescribe ferric iron preparations due to their optimal absorption and lack of side effects.

In children younger age IDA is predominantly of nutritional origin and most often represents a combination of deficiency not only of iron, but also of protein and vitamins, which necessitates the prescription of vitamins C, B1, B6, folic acid, and correction of protein content in the diet.

Since 50-100% of premature babies develop late anemia, from 20-25 days of life at a gestational age of 27-32 weeks, body weight 800-1600 g, (during a decrease in blood hemoglobin concentration below 110 g/l, the number of red blood cells is lower 3.0 ґ 10 12/l, reticulocytes less than 10%), in addition to iron supplements (3-5 mg/kg/day) and sufficient protein supply (3-3.5 g/kg/day), erythropoietin is prescribed s.c. , 250 units/kg/day three times a day for 2-4 weeks, with vitamin E (10-20 mg/kg/day) and folic acid(1 mg/kg/day). Longer use of erythropoietin - 5 times a week, followed by its reduction to 3 times, is prescribed for children with severe intrauterine or postnatal infection, as well as for children with a low reticulocyte response to therapy.

Parenteral iron supplements should be used strictly only for specific indications, due to the high risk of local and systemic adverse reactions.

The daily dose of elemental iron for parenteral administration is:
for children 1-12 months - up to 25 mg/day
1-3 rocks - 25-40 mg/day
over 3 years of age - 40-50 mg/day
The course dose of elemental iron is calculated using the formula:
MTґ (78-0.35ґ Hb), where
MT - body weight (kg)
Hb - child’s hemoglobin (g/l)
The course dose of an iron-containing drug is KJ: SZhP, where
KID - course dose of iron (mg);
SIP - iron content (mg) in 1 ml of the drug
Course number of injections - KDP: SDP, where
KDP - course dose of the drug (ml);
DDP - daily dose of the drug (ml)

Blood transfusions are carried out only for health reasons, when acute massive blood loss occurs. Preference is given to red blood cells or washed red blood cells.

Ferrotherapy contraindications:

• aplastic and hemolytic anemia
• hemochromatosis, hemosiderosis
• sideroachrestic anemia
• thalassemia
• other types of anemia not associated with iron deficiency in the body

4. Prevention
Antenatal: women from the 2nd half of pregnancy are prescribed iron supplements or multivitamins fortified with iron.
In case of repeated or multiple pregnancy, it is necessary to take iron supplements during the 2nd and 3rd trimester.
Postnatal prophylaxis for children from high-risk groups for developing IDA.

This group is formed by:

• all premature babies
• children born from multiple pregnancy and with a complicated course of the second half of pregnancy (gestosis, placental insufficiency, complications of chronic diseases)
• children with intestinal dysbiosis, food allergies
• children who are bottle-fed
• children who grow up ahead of generally accepted standards of physical development.

Regular diagnosis of the possible development of IDA is provided and, when it is determined, preventive doses of iron supplements are prescribed (0.5-1 mg/kg/day) for 3-6 months.

5. Dispensary observation
After normalization of blood counts general analysis blood tests are performed once a month during the first year, then quarterly for the next 3 years.