Diseases in the body that are caused by vitamin B12 deficiency have several medical names:

History of the disease

The history of the disease of this species goes back to 1855, when the British doctor Addison gave a detailed explanation of this disease, and in 1872 the German doctor Birmer supplemented the description of this pathology, and after that the lack of vitamin B12 began to be characterized as anemia, which is of a malignant nature.

At that time, there were no methods for the correct diagnosis of pathology, as well as qualified treatment, so hemoglobin dropped to 30.0 g / l and below, the person fell into a coma, which led to death.

Only in the 20th century in 1926, a discovery was made, which was assessed by the Nobel Prize, that anemia with vitamin B12 deficiency is the inability of the stomach organ to produce a specific enzyme that helps the absorption of this vitamin from the digestive system.

Icb code 10

According to the international classification of diseases of the tenth revision of ICD-10, this pathology belongs to class D 51, "Vitamin-B12-deficiency anemia".

Megaloblastic type of anemia

Pernicious (with B12 deficiency) anemia refers to the megaloblastic form of anemia, and is rarely combined with another megaloblastic anemia - folic acid deficiency.

Megaloblastic anemia is a rather rare form of pathology in which there is a deviation from the normal absorption of the digestive system folic acid, vitamin B12 and cyanocobalamin substances.

As a result, there is a lack of vitamins of group B: B12 and B9 in the body.

Megaloblasts are modified erythrocytes that are synthesized in cells by DNA and RNA. Megaloblasts appear in bone marrow cells as a consequence of an abnormality in the synthesis procedure. This is manifested in morphological changes in the composition of cells.

What is common and what is the difference between the 2 types of megaloblastic anemias?

B vitamins fall into human body with products of animal origin. In the stomach, they bind to gastromucoprotein and are absorbed in the small intestine. For normal functioning the body's daily dosage of vitamin B12 should be 7 mcg.

The reserve of this vitamin is in the liver - no more than 5 mg. The body's need for folic acid is about 100 mcg per day. Vitamin B9 reserve - up to 10 mg.

Violations in the synthesis of DNA molecules leads to the inability of these bone marrow cells to rapidly divide.

These cells include:

• The membranes of the mucous system;
• Systems digestive tract;
• Bone marrow cells;
• Skin cells.

The cells of the hematopoietic system (hematopoietic) are cells that multiply faster than others. Therefore, the indicators (reduced level of erythrocytes and low hemoglobin coefficient) in the hematopoietic system characterize the first manifestations of megaloblastic anemia.

With the manifestation of anemia, the following signs of the hemolytic nature of anemia are often observed:

• Pathology of thrombocytopenia - a decrease in the index in the blood of platelets;
• Disease neutropenia - a reduced rate of neutrophilic leukocytes;
• Blood pathology agranulocytosis - a decrease in the leukocyte index;
• Disease monocytosis - a decrease in monocyte molecules;
• Decreased synthesis of reticulocytes.

Difference and relationship between folate deficiency B9 anemia and vitamin B deficiency - B12:

• Vitamin B12 is involved in the synthesis of folic acid molecules. The acid is part of the thymidine molecule, which is a component of the DNA molecule. With the well-coordinated work of these components, and with their required amount for the biochemical reaction, the normal formation of blood cells and cells for the normal functioning of the digestive tract occurs;
• The functional responsibilities of vitamin B12 are to help synthesize and break down in the body fatty acids... With a deficiency of cyanocobalamin molecules, a violation of the coordinated reaction occurs, and methylmalonic acid is deposited, which has a detrimental effect on the atoms of neurons. There is also a decrease in the synthesis of myelin, which forms a sheath for the fibers of nerve cells.

Folic acid is not involved in the breakdown of fatty acids and is not involved in the formation of sheaths for nerve fibers.

With a deficiency of vitamin B12, the doctor prescribes taking medications with folic acid, then it activates erythropoiesis, but only until this acid becomes in excess in the body.

With an overdose of folic acid, the following occurs:

• Disorder in the nervous system;
• Degenerative changes in the bone spinal cord;
• Combined sclerosis with loss of motor functions;
• Funicular type of myelosis.

Symptoms of anemia

Symptoms of B12 deficiency anemia and folic acid (as well as its lack) are classified according to the following directions in the manifestation of pathology:

• Anemic syndrome in the hematopoietic system;
• Gastroenterological symptoms - disorders in the digestive tract;
• Neurological;
• Symptoms in violation of the structure of the brain.

The classification of the anemic direction is manifested in the following symptoms:

• Great dizziness;
• Weakness of the whole body;
• Fainting state;
• Rapid contraction of the heart muscle (sinus type of tachycardia);
• Dyspnea;
• Painful sensations in the chest;
• Noise in ears;
• Ambiguity in the perception of objects by the organs of vision;
• Yellow tint of the skin (the shade gives high level in the blood of bilirubin).

Gastroenterological symptoms:

Neurological syndrome:

• Birmer anemia - Addison-Birmer disease;
• Light tingling sensation in fingers and toes;
• Constant chills
• Shakiness in motion;
• Numbness in the lower extremities;
• Lethargy of the legs;
• The sensitivity of the skin disappears;
• Difficulty moving.

Abnormalities in the brain of this type of anemia, as well as disturbances in work spinal cord:

• Lack of memory;
• Hallucinations;
• The state of being lost;
• Overexcitation;
• Feeling of constant irritation;
• Coma state;
• Muscle cramps.

With anemia, vitamin B12 deficiency, as well as with iron deficiency anemia, there are signs of severe hypoxia in the body:

Forms of development

The pathogenesis of anemia with insufficient disappearance of the molecules of B vitamins, namely B12 and B9, into the body, which affects the level of hemoglobin molecules, which is located in erythrocytes and is responsible for the delivery of oxygen atoms to all cells of the human body.

Anemia is divided into forms according to the index in the composition of blood plasma of hemoglobin molecules.

The lower the hemoglobin index, the more severe the course of the deficiency pathology:

• Light stage of development and course - hemoglobin index from 90.0 to 110.0 grams per liter of biological fluid;
• Moderate severity - hemoglobin index from 70.0 to 90.0 grams per one liter of blood plasma;
• Severe stage of the course of this pathology - the coefficient of red pigment does not exceed 70.0 and decreases even below this indicator.

The standard indicators for the amount of hemoglobin in the blood in men are 130.0 - 160.0 g / l.

For women, the standard is 120.0 - 135.0 g / l.

B12 deficiency anemia in children

The main types of etiology of anemia with a lack of this vitamin B childhood are:

• Changes in the baby's microflora;
• There is not enough of this vitamin in the child's body;
• The presence of worms in the body;
• Castle factor during the period of intensive growth of the child.

Clinical indicators and manifestations of this type pathologies are similar to the symptoms of an adult, but there is characteristic symptoms in the child's body:

• Severe dental caries from a young age;
• Persistent stomatitis that begins in infancy;
• Changes in the eyeball;
• Changes in the nail plate - the plate is weak, brittle;
• Impaired attention and intelligence - decreased performance in school.

In the decoding of the results of the clinical laboratory, the following values ​​are:

• Low hemoglobin index;
• Decreased number of erythrocyte molecules;
• The chromaticity index is increased - by more than 1.5;
• In the molecules of erythrocytes, Kebot's rings, as well as Jolly's bodies, are present in such an amount that analysis determines them;
• Reticulocytes are increased;
• Increased lymphocyte count;
• Platelets, as well as leukocytes - in small quantities;
• Biochemistry revealed megaloblasts in the bone marrow puncture.

To help laboratory parameters, to establish the diagnosis of B12 deficiency anemia, an instrumental method for diagnosing the child's body is used:

Treatment of anemia in a child with B12 deficiency consists in saturating the body cells with these vitamins. Vitamin medication course for 15 calendar days. A high-calorie diet is also prescribed, in which foods with vitamin B12 and folic acid are present.

To replenish the vitamin molecules in the body, the drug Cyanocobalamin is prescribed. The initial dosage of this drug is from 30.0 mcg to 50.0 mcg, when taken daily. This drug is injected inside by injection.

The dosage is calculated individually by the treating doctor. The drug course is carried out in children under the strict supervision of a specialized specialist.

After the end of the course of treatment in preventive purposes and as a maintenance treatment, 100.0 - 250.0 mcg 2 times a month.

The normative indicators of the vitamin cyanocobalamin in the child's body:

Etiology

Vitamin B12 benefits the body when it is absorbed in the intestines. For the reaction of this absorption to occur, an enzyme is needed that is produced by the inner parts of the stomach - Castle's enzyme.

Without the formation of an enzyme, the vitamin B12 molecule is excreted outside the body without getting it for biochemical processes, through feces.

In case of B12 deficiency anemia, Castle's enzyme is not synthesized in the stomach, therefore the vitamin that enters the food is also not absorbed through the intestines.

There is a supply of vitamin B12 molecules in the liver cells, which, if used wisely, can be sufficient for 5 calendar years. As a result, anemia occurs after a while, after the stomach has ceased to produce this factor.

Castle factor deficiency is the main cause of the pathology of B12 deficiency anemia.

Causes

The lack of cyanocobalamin is caused by the following factors:

• Low vitamin B12 foods (main reason)... Cyanocobalamin is found in animal products. Vegetarianism is the main risk factor for a B12 deficiency in food;
• The function of the Castle factor is impaired... With atrophy of mucosal cells, functionality internal factor does not appear, or it decreases. This reason atrophy is genetic, congenital, with gastritis of the stomach, with exposure to the stomach of toxic elements (intoxication of the body), as well as the effect on the antibody factor;
• Absence or partial loss of receptors that are necessary for the factor. This pathology develops with Crohn's disease, with neoplasms in the small intestine (cancer), with tuberculosis disease, with intestinal infantilism, as well as with enteritis in chronic stage course of pathology;
• Absorption of B12 molecules by worms and pathogens... It is necessary to treat this pathology with therapy against competitors that absorb cyanocobalamin;
• With pathology of the pancreas... With this pathology, there is a deviation in the breakdown of the protein protein, which is the link between the factor and vitamin B12;
• Genetic hereditary congenital anomaly- This is a reduced rate of transcobalamin synthesis in the body, which leads to a disruption in the transport of cyanocobalamin molecules to bone marrow cells.

For folate deficiency anemia, food etiology is not suitable, because vitamin B9 is present in every plant and animal product. This B vitamin does not need the help of a factor and is absorbed on its own.

Folio deficiency problems begin when the following reasons appear in the body:

• Poor diet
• Small food intake;
• Starvation;
• Anorexia;
• Old age of the patient, at this age there is a difficult assimilation of vitamins from food;
• Reception of alcoholic beverages. At alcohol addiction, a person cannot eat well;
• Pathology in the intestines that prevents vitamins from being absorbed by the body;
• Crohn's disease;
• Celiac disease pathology;
• Malignant neoplasms in the intestines;
• Increased need for vitamin B12 and folic acid in a woman during the period of prenatal formation of the baby. In pregnant women, the consumption of these products with food should be increased in order to avoid fetal hypoxia;
• Increased consumption of B9 in psoriasis pathology;
• When taking anticonvulsants medications, there is a deficiency of vitamins B9 and B12.

Vitamin deficiency occurs when taking medications

Diagnostics

When making this diagnosis - B12 deficiency anemia, the doctor first of all in the diagnosis collects an anamnesis - when and under what circumstances there was a pronounced symptomatology of anemia, with its weakness and manifestations of pathology in the process of digestion.

It is also necessary to find out whether the patient has diseases that occur in the chronic stage, as well as to bring information about possible genetic hereditary congenital diseases.

After the anamnesis, the patient's skin is examined, severe symptoms on the skin.

Also, the doctor measures the index blood pressure(with anemia, the pressure is lowered), as well as the heart rate (often the pulse is rapid).

After this inspection, based on external signs, appointed laboratory diagnostics(blood test), as well as a list of instrumental studies:

• General blood analysis;
• Biochemical analysis of blood composition;
• Urine on general analysis;
• Bone marrow puncture;
• Electrocardiography (ECG);
• Ultrasound of the liver and spleen;
• Bowel ultrasound;
• Ultrasound of the stomach.

When decoding the general analysis, the whole picture of blood is visible, the indicators of each element in its composition. According to this analysis, with anemia of vitamin B12 deficiency, a decrease in erythrocyte molecules, as well as a reduced synthesis of reticulocytes, is seen.

The level of red pigment (hemoglobin) is reduced, platelets are also reduced, which provokes hypoxia. Chromaticity increases with anemia and reaches more than 1.50 (with a norm of 0.860 - 1.050).

During the analysis, the presence of proteins in urine is observed, and the possible detection of concomitant pathologies.

Biochemistry is the most valuable analysis for detecting abnormalities in the structure and composition of blood.

In the composition of biochemistry, the following indicators are detected in B12 deficiency anemia:

• Cholesterol index often elevated with anemia;
• The presence of creatinine;
• Blood glucose;
• Uric acid;
• Electrolyte indicators of calcium, potassium and sodium molecules;
• Lactate dehydrogenase is an enzyme in the liver cells that promotes the absorption of iron by cells. Index biological reactions for the synthesis of erythrocytes and hemoglobin;
• B vitamins are reduced. The B12 index is low.

The blood hemogram shows the hematocrit number, the percentage of all types of leukocytes - the leukocyte formula is established.

Myelogram, or indicators of bone marrow puncture, determines the level of production of erythrocyte molecules, as well as megaloblasts in the blood, which confirms the megaloblastic nature of hematopoiesis in the human body.

The instrumental technique determines deviations from the standard indicators structure internal organs and also detects violations in their functionality.

Therapy for B12 deficiency anemia

Therapy for B12 deficiency anemia begins with treating the underlying cause of the deficiency - this is curative therapy for the destruction of helminths, normal and balanced nutrition, as well as surgical technique treatment of malignant neoplasms.

For the complex treatment of anemia, the drug B12 is administered into the body at a dosage of 200.0 μg - 250.0 μg per day. The drug is injected into the muscle tissue, or injected under the skin of the human body.

If the anemia has affected the centers nervous system, then the scheme drug therapy this is the first 3 calendar days dosage of vitamin 1000.0 mcg per day, and subsequent treatment according to the prescribed scheme. The treatment regimen, as well as the dosage of B12, is prescribed by the attending doctor and depends on the degree of vitamin B12 deficiency in the body, which caused the anemia.

After stabilization of this vitamin in the body, to maintain it on normal level, in the treatment, the drug B12 is used at 100.0 μg - 200.0 μg 1 time per one calendar month.

Clinical guidelines for rapid replenishment of erythrocytes in the blood - the introduction of intravenous erythrocyte mass, which can restore the destroyed balance in the blood plasma of the human body.

Complicated form of B12 deficiency anemia

If not take emergency measures in treatment, the consequences of this type of anemia can be quite serious and pose a threat to the patient's life:

• Coma in which the patient does not respond to external stimuli. Coma can occur from cerebral hypoxia with anemia and can cause death;
• Severe anemia, which significantly worsens the condition of the body and triggers irreversible consequences in it. This degree occurs when the hemoglobin index is lower than 70.0 g / l;
• Funicular myelosis- this is damage to the cells of the spinal cord, as well as nerve endings peripheral departments organism. Damage to the connective nerve fibers of the spinal cord with the centers of the brain, as well as with all internal organs and systems of the body. With these violations, the sensitivity of the limbs decreases, unsteadiness appears in movements, and the period of progression of myelosis - the sensitivity disappears altogether and the person is not capable of independent movement;
• Destruction of cells of internal organs, which subsequently leads to the non-functionality of this organ (heart, liver and spleen cells, digestive tract, kidney cells, respiratory system are affected).

If the treatment process began too late, then complications in the nervous system cannot be restored. These destruction are irreversible.

Prophylaxis

Prevention is mainly aimed at improving B12 intake through foods:

• Eating animal products with a large amount of B12 in them;
• Timely therapy of pathologies that can cause B12 deficiency and provoke anemia;
• After surgery on the organs of the digestive tract, take medications to maintain the level of this vitamin.

Diet for this form of anemia

A balanced diet is especially necessary during the period of intrauterine development of a child, since the formation of an infant depends on the intake of vitamins in the body of a pregnant woman, as well as the occurrence of intrauterine pathologies that are revealed after birth.

During pregnancy, the need for vitamin B12 increases by 50.0%.

products	amount of B12 in μg
Calf liver	60.0
Liver of a young pig	30.0
Chicken liver	16.0
Mackerel fish	12.0
Rabbit meat	4.30
Veal	2.60
Fish perch	2.40
· pork	2.0
· eggs	0.40
Fat sour cream

In case of B12 deficiency anemia, a diet is used - table number 11. This diet should increase the content of protein and vitamin B12 in the body. The method of cooking food is common. You need to eat 5 times a day.

Energy value of diet number 11:

• Proteins - 110.0 grams - 130.0 grams (60.0% animal origin, 40.0% vegetable);
• Fat - 100.0 grams - 120.0 grams (80.0% - animals and only 20.0% vegetable);
• Carbohydrates - 400.0 grams - 450.0 grams;
• Salt - no more than 15.0 grams;
• Purified water 1.5 liters.

healthy foods for B12 deficiency anemia	prohibited foods
Veal, pork, chicken liver	· milk
· Salo	Baking
· butter	Confectionery sweet products
Mackerel fish	· tea
Meat: veal, rabbit, pork	Caffeinated drinks
· eggs	· Coca Cola
Fat sour cream	· alcoholic drinks
Fat-free cottage cheese	Do not use vinegar in cooking
· hard cheese	Sugary carbonated drinks
Soft cheese
Legumes: peas, lentils
Vegetables: carrots, potatoes, cabbage, beets, tomatoes
Fruits of all sorts
Berries of all types
Vegetables with a green color are rich in iron
Garden greens
Mineral water

Life prognosis for B12 deficiency anemia

Favorable prognosis	Poor prognosis
with early treatment	with late therapy
Indicators in peripheral blood come back to normal in 45 - 50 calendar days.	· Pronounced anemia, which does not respond well to therapy.
· Hemoglobin returns to normal within 30 - 60 calendar days.	· Symptoms of damage to the centers of the nervous system, which is not restored.
· The B12 index is kept within the normative framework and anemia does not show its harmful effects on the body.	· The body does not perceive drug B12, which is fraught with anemic type of coma.
	· With a genetic form of anemia, in most cases it is impossible to achieve a complete cure. Lifelong maintenance therapy in 70.0% of these patients.

Candidate of Medical Sciences, Associate Professor V.A. Tkachev

V 12 - DEFICIENT ANEMIA

V 12 -deficient anemia Is a severe progressive anemia that occurs when the absorption of vitamin B 12 from food is impaired due to a decreased (or in the absence) secretion of internal gastric factor.

The nomenclature of the name of this disease is different, and it is often referred to in the literature as pernicious anemia (perniciosa - fatal), malignant Addison-Birmer disease (by the names of the authors), as well as megaloblastic anemia (by the type of hematopoiesis).

Persons over 40 are ill. Women are susceptible to this disease twice as often as men and, above all, at the age of 50-60 years. There are known cases of B 12 -deficiency anemia in children fed with goat's milk or powdered milk formulas. The incidence ranges from 20 to 60 cases per 10,000 population.

Historical reference. The first description of this disease was made by Coombs in 1822 and called it severe primary anemia. In 1855 the physician Addison described this suffering as "idiopathic anemia." In 1872 Birmer published the results of observation of a group of patients suffering from progressive pernicious anemia. However, the possibility of curing this disease appeared only in 1926, when Minot and Murphy discovered a pronounced therapeutic effect from the administration of raw liver.

Three years later, the American physiologist Castle showed that raw meat, liver, yeast, processed with gastric juice of a healthy person, have the property of causing remission in a patient with pernicious anemia. Castle's studies formed the basis of the concept that as a result of the interaction of two factors - external, contained in raw meat, raw liver, yeast, and internal, produced by the gastric mucosa, an antianemic compound is created, which ensures the physiological maturation of bone marrow cells.

The nature of the external factor has been established - it is cyanocobalamin (vitamin B 12 ) ... Vitamin B 12, according to the needs of the body, is used not only for hematopoiesis in the bone marrow, but also for the normal functioning of the nervous tissue and digestive organs.

A complex compound consisting of peptides (appearing during the conversion of pepsinogen to pepsin) and mucoids (secreted by additional cells of the gastric mucosa) was named gastromucoprotein or intrinsic Castle factor... The role of the intrinsic factor (gastromucoprotein) is to form a complex with vitamin B 12, which ensures the transport of cyanocobalamin through the intestine and prevents its breakdown and inactivation. Resorption (absorption) of vitamin B 12 occurs in ileum... Its further entry into the portal bloodstream is carried out with the help of protein carriers: transcobalamin-1 (-globulin) and transcobalamin-2 (-globulin), which form a protein-B 12 -vitamin complex that can be deposited in the liver.

Etiology. The leading factor in the etiology of the disease is endogenous vitamin B deficiency 12 , resulting from a violation of its absorption due to the cessation of the secretion of an intrinsic factor (gastromucoprotein).

Suction problems B 12 may result from injury gastrointestinal tract inflammatory or malignant process, after subtotal or total removal of the stomach, after extensive resection of part of the small intestine... In rare cases, pernicious anemia develops with normal secretion of internal gastric factor and is due to congenital absence of transcobalamin-2, with which vitamin B 12 binds and is delivered to the liver, or as a result lack of a protein acceptor in the intestine(perceiving) vitamin B 12, which is necessary for the flow of cyanocobalamin from the intestines into the bloodstream. In some cases, there is genetic factor of development In 12-deficiency anemia due to congenital disorders in the production of gastric factor or the presence of antibodies against parietal cells.

The following factors can also lead to the occurrence of B 12-deficiency anemia:

impaired absorption of B 12 in the small intestine as a result chronic enteritis or celiac disease;

competitive absorption of vitamin B 12 in the small intestine wide ribbon or microorganisms;

complete exclusion of food of animal origin;

long decreased exocrine pancreatic activity, the consequence of which is a violation of the breakdown of protein R, without which vitamin B 12 cannot bind to mucopolysaccharide;

long-term appointment some drugs : methotrexate, sulfasalazine, triamterene, 6-mercaptopurine, azathioprine, acyclovir, fluorouracil, cytosar, phenobarbital, etc.

Pathogenesis. Violation of hematopoiesis with B 12 -deficiency anemia is characterized by megaloblastic type for all three blood growths: erythroid, granulocytic and megakaryocytic. The ineffectiveness of red hematopoiesis is noted: impaired differentiation of erythroid cells and the appearance of abnormal cells such as promegaloblasts, megaloblasts ( big size cells with basophilic cytoplasm and a nucleus containing nucleoli).

As a result of defective metabolism of folic acid (due to B 12 deficiency), which is involved in the formation of DNA, cell division is impaired. The consequence of this is a pronounced intramedullary death of erythroid elements and a decrease in the number of erythrocytes in the periphery.

Due to the incompetence of the cellular elements of the blood, it is strengthened hemolysis, which is manifested by hyperbilirubinemia, urobilinuria, an increase in stercobilin in the feces.

Pathological changes characterized by general anemia, yellowness of the skin and mucous membranes, fatty degeneration of the myocardium, liver, kidneys. The bone marrow is juicy, crimson in color due to hyperplasia.

On the part of the digestive system, atrophic changes in the papillae of the tongue (their smoothness), inflammatory changes in it (glossitis), aphthous rashes, cracks (Gunther's glossitis), as well as atrophy of the mucous membrane of the cheeks, palate, pharynx, esophagus are revealed. The greatest atrophy is recorded in the stomach, which is characterized by thinning of its walls, the formation of polyps. The intestinal mucosa is also atrophied. The spleen is usually normal or enlarged.

Hepatomegaly is unexpressed. Revealed hemosiderosis in the liver, spleen, kidneys (rusty tint in the cut) as a result of hemolysis of erythrocytes.

Dystrophic changes are noted in the nerve fibers of the tongue (nerve plexuses of Meissner and Auerbach), as well as in the posterior columns of the spinal cord (focal swelling with disintegration of myelinated nerve fibers).

Clinical manifestations In 12-deficiency anemias often develop gradually: weakness, malaise, dizziness, dyspeptic disorders, tinnitus, and a tendency to obesity increase. Rarely, the disease begins acutely, with a rise in body temperature to 38C, severe weakness.

Anemic syndrome characterized by lethargy, pallor of the skin with a lemon-yellow tinge, sometimes (in 12% of patients) subicteric sclera. In peripheral blood, anemia is recorded, more often (58%) severe, with an increase in the color index to 1.4, a decrease in reticulocytes to 0.5 - 1.0% (in a third of patients - reticulocytosis), poikilocytosis and the presence of Jolly's bodies and Cabot's rings in erythrocytes. Leukopenia, lymphocytosis, but thrombocytopenia are often detected.

In the bone marrow, signs of a megaloblastic type of hematopoiesis are determined.

Gastric dyspepsia syndrome(37,% of observations) is manifested by belching, nausea, loss of taste, decreased appetite up to aversion to food, heaviness in the epigastrium, sometimes dysphagia, burning sensation of the tongue, oral mucosa. EGDS reveals atrophic changes in the mucous membrane of the esophagus and stomach.

Intestinal dyspepsia syndrome characterized by unstable stools, weight loss.

Glossitis manifested by the presence of a “scalded” (red) or “varnished” tongue with cracks. Pain in the tongue is noted in 30% of patients with B 12 deficiency anemia.

Jaundice syndrome happens in 50% of patients and is manifested by subicteric sclera and hyperbilirubinemia.

Funicular myelosis syndrome(sensory ataxia - impaired coordination of movements) is observed in patients with B 12 deficiency anemia in 11% of cases and develops as a result of impaired proprioceptive sensitivity due to atrophic processes in the posterior horns of the spinal cord. There may be other symptoms of damage to the nervous system: paresthesia, dysfunction pelvic organs, decreased reflexes.

Intercostal neuralgia syndrome occurs significantly more often (up to 30% of cases) than signs of funicular myelosis, manifests itself as neuralgic pain along the intercostal space and is also due to functional insufficiency of the nerve tissue of the conductors.

Some patients have lesions of the cranial nerves (visual, auditory, olfactory), symptoms of spinal paralysis (spastic paraparesis with increased reflexes and clonuses). Central scotoma (visual field defect) with loss of vision may be detected.

External changes central nervous system may manifest psychomotor agitation syndrome(manic state with euphoria or depression syndrome with impaired memory and criticism - megaloblastic dementia).

Cardiac syndrome(in 15–20% of cases) is characterized by shortness of breath, palpitations, pain in the region of the heart, myocardial dystrophy. During auscultation of the heart, a functional anemic murmur is heard. On the ECG, a decrease in ST, an expansion of the ventricular complex is determined.

Edematous syndrome occurs with B 12 -deficiency anemia in 80% of cases and manifests itself as peripheral edema, which can reach the degree of anasarca, as a result of circulatory failure.

Enlarged liver ( hepatomegaly syndrome) occurs in 22% of patients, an enlarged spleen ( splenomegaly syndrome) in 10% of cases.

With untreated B12 deficiency anemia, pernicious coma syndrome, manifested by cerebral ischemia, loss of consciousness, areflexia, a drop in body temperature, a decrease in blood pressure, vomiting, and involuntary urination.

With the aim of diagnosis of the disease a thorough hematological examination is carried out, including the study pictures of peripheral blood, sternal punctate and serum factors involved in hematopoiesis. An accurate diagnosis is very important because these patients in some cases require lifelong treatment.

Hypersegmentation of neutrophils(more than five nuclear lobes) of peripheral blood is the first hematological pathology in megaloblastic status. In a healthy person, up to 2% of hypersegmented neutrophils can circulate in the blood. In patients with megaloblastic anemia, the number of hypersegmented neutrophils exceeds 5%.

For bone marrow hematopoiesis is characterized by megaloblastic type, for which irritation of the red sprout and the appearance of megaloblasts are typical. The bone marrow is hypercellular due to an increase in the number of nucleated cells of the red row. As a result of a violation of cell division, erythroid cells become very large ( megaloblasts). They are characterized by large size, delicate structure and unusual location of chromatin in the nucleus, asynchronous differentiation of the nucleus and cytoplasm.

In blood serum in patients with B 12 deficiency anemia increased concentration of bilirubin, iron, ferritin(iron-containing liver protein). Serum lactate dehydrogenase (LDH) activity is significantly increased and increases as the disease progresses. Level serum cyanocobalamin usually low, but may be normal.

Differential diagnosis held with folate deficiency anemia... Folic acid deficiency is usually observed in more young age, is not accompanied by atrophic changes in the gastric mucosa and neurological symptoms.

To exclude folate deficiency anemia, the Schilling test is performed: vitamin B 12 is administered parenterally, which is determined in the urine in minimal amounts with B 12 deficiency anemia and in large quantities with folate deficiency. It is important to take into account that the appointment of folic acid to patients with B 12 -deficient anemia rapidly contributes to the development of funicular myelosis.

It should be remembered that symptomatic megaloblastic anemia is caused by tumors of the stomach, small and cecum, as well as helminthic invasion(helminthic B 12 - deficiency anemia), which must be excluded when verifying the diagnosis.

Differentiation should be done with erythromyelosis(initial forms of manifestation of leukemia), which are accompanied by anemia, proceeding with an increased content of vitamin B 12 in the blood and resistant to treatment with cyanocobalamin.

When carrying out the differential diagnosis of B 12-deficiency anemia, it is necessary to establish its causes.

Treatment B 12-deficiency anemia includes parenteral administration of vitamin B 12 or hydroxycobalamin (a metabolite of cyanocobalamin) in doses that meet the daily requirement and double the depot reserves. Vitamin B 12 is injected at 1000 mcg intramuscularly daily for two weeks, then once a week until the hemoglobin level normalizes, after which they switch to the introduction once a month throughout life.

Oxycobalamin on pharmacological properties is close to cyanocobalamin, but in comparison with the latter it turns into an active coenzyme form in the body more quickly and remains in the blood longer. Oxycobalamin is administered at a dose of 500–1000 mcg every other day or daily. In the presence of neurological symptoms, it is necessary to administer the drug at a dose of 1000 mcg every two weeks for six months.

With funicular myelosis, massive doses of cyanocobalamin 1000 mcg are prescribed daily for 7-10 days, then twice a week until the neurological signs disappear.

The initiation of cobalamin therapy quickly improves the well-being of patients. Bone marrow erythropoiesis turns from megaloblastic to normoblastic already 12 hours after the administration of vitamin B 12. Therefore, the appointment of vitamin B 12 in a coma is an urgent measure. Reticulocytosis appears on days 3-5, its peak (reticulocytic crisis) is most pronounced on days 4-10. The concentration of hemoglobin is normalized after 1–2 months. Hypersegmentation of neutrophils lasts up to 10-14 days.

Red blood cell transfusion are indicated for the urgent elimination of symptoms of hypoxia.

After cobalamin therapy, severe hypokalemia... Therefore, in the course of treatment with vitamin B 12, it is necessary to carefully monitor the potassium content in the blood and, if necessary, carry out replacement therapy.

Cobalamin treatment should be administered to all patients after total gastrectomy... To prevent an exacerbation, vitamin B 12 is administered once every two weeks, 100-200 mcg.

Clinical examination. Patients with 12-deficiency anemia are subject to dispensary observation, during which the state of peripheral blood is monitored 1-2 times a year, as well as the treatment of diseases and conditions that led to the development of this type of anemia.

There are different regimens for cobalamin maintenance therapy. When appointing cyanocobalamin recommended for life, annual prophylactic three-week courses of 400-500 mcg every other day or monthly administration of 500-1000 mcg of the drug. Hydroxycobalamin recommended annual preventive courses of one injection per week (1 mg) for 2 months.

Description of B12-deficiency anemia:

B12-deficiency anemia is a disease caused by impaired blood formation due to a lack of vitamin B12 in the body. Bone marrow and tissues of the nervous system are especially sensitive to the deficiency of this vitamin.

Impaired absorption of vitamin B12 (cobalamin) causes pernicious anemia. This vitamin, found in meat and vegetables, is normally absorbed actively in the ileum (the lower part of the small intestine that connects to the large intestine). However, vitamin B12 can be absorbed and enter the bloodstream only in combination with the so-called internal factor - a protein formed in the stomach. Without intrinsic factor, vitamin B12 remains in the intestines and is excreted in the feces. In case of pernicious anemia, an internal factor is not produced in the stomach, vitamin B12 is not absorbed, and anemia develops even with sufficient intake of this vitamin with food. But since the liver has a large supply of vitamin B12, anemia develops only 2-4 years after its normal absorption in the intestine stops.

With a deficiency of vitamin B12, not only the maturation of erythrocytes is delayed, but the nervous system is also affected - tingling appears in the hands and feet, loss of sensitivity in the legs (feet) and arms, muscle spasms. Other symptoms may include a specific type of color blindness (impaired perception of yellow and blue colors), tongue inflammation or burning sensation, weight loss, darkening of the skin, confusion, depression, and decreased intellectual capacity.

Pathogenesis of B12-deficiency anemia:

The role of cyanocobalamin and folic acid in the development of megaloblastic anemia is associated with their participation in wide range metabolic processes and metabolic reactions in the body. Folic acid in the form of 5,10-methylenetetrahydrofolate is involved in the methylation of deoxyuridine, which is necessary for the synthesis of thymidine, and 5-methyltetrahydrofolate is formed.

Cyanocobalamin is a cofactor of a methyltransferase catalytic reaction that resynthesizes methionine and simultaneously regenerates 5-methyltetrahydrofolate to tetrahydrofolate and 5.10 methylenetetrahydrofolate.

In case of deficiency of folates and (or) cyanocobalamin, the process of incorporating uridine into the DNA of developing hematopoietic cells and the formation of thymidine is disrupted, which causes DNA fragmentation (blocking its synthesis and disrupting cell division). In this case, megaloblastosis occurs, there is an accumulation of large forms of leukocytes and platelets, their early intraosseous destruction and a shortening of the life of circulating blood cells. As a result, hematopoiesis is ineffective, anemia develops, combined with thrombocytopenia and leukopenia.

In addition, cyanocobalamin is a coenzyme in the conversion of methylmalonyl-CoA to succinyl-CoA. This reaction is necessary for the metabolism of myelin in the nervous system, and therefore, with a deficiency of cyanocobalamin, along with megaloblastic anemia, damage to the nervous system is noted, while with a deficiency of folates, only the development of megaloblastic anemia is observed.

Cyanocobalamin is found in foods of animal origin - liver, kidneys, eggs, milk. Its reserves in the body of an adult (mainly in the liver) are large - about 5 mg, and if we consider that the daily loss of vitamin is 5 μg, then the complete depletion of reserves in the absence of intake (malabsorption, with a vegetarian diet) occurs only after 1000 days ... Cyanocobalamin in the stomach binds (against the background of an acidic reaction of the environment) with an intrinsic factor - glycoprotein produced by the parietal cells of the stomach, or other binding proteins - R-factors present in saliva and gastric juice... These complexes protect cyanocobalamin from destruction during transport along the gastrointestinal tract. In the small intestine at an alkaline pH value, under the influence of pancreatic juice proteinases, cyanocobalamin is cleaved from R-proteins and combines with an internal factor. In the otic intestine, the intrinsic factor complex with cyanocobalamin binds to specific receptors on the surface of epithelial cells, the release of cyanocobalamin from intestinal epithelial cells and transport to tissues occurs with the help of special blood plasma proteins - transcobalamins 1,2,3, and cyanocobalamin is transported to hematopoietic cells mainly transcobalamin 2.

Folic acid is found in green leaves of plants, fruits, liver, and kidneys. Folate stores are 5-10 mg, with a minimum requirement of 50 mcg per day. Megaloblastic anemia may develop after 4 months complete absence dietary folate intake.

Symptoms of B12 deficiency anemia:

B12-deficiency anemia develops relatively slowly and may be asymptomatic. Clinical signs of anemia are nonspecific: weakness, fatigue, shortness of breath, dizziness, palpitations. Patients are pale, subicteric. There are signs of glossitis - with areas of inflammation and atrophy of the papillae, a lacquered tongue, there may be an increase in the spleen and liver. Gastric secretion is sharply reduced. Fibrogastroscopy reveals atrophy of the gastric mucosa, which is also confirmed histologically. There are also symptoms of damage to the nervous system (funicular myelosis), which do not always correlate with the severity of anemia. Demyelination of nerve fibers lies at the core of neurological manifestations. Distal paresthesias, peripheral polyneuropathy, sensory disorders, increased tendon reflexes are noted.

Thus, B12-deficiency anemia is characterized by a triad:
- blood damage;
- damage to the gastrointestinal tract;
- damage to the nervous system.

Diagnostics of the B12-deficiency anemia:

1. Clinical blood test
- a decrease in the number of red blood cells
- decrease in hemoglobin
- an increase in the color indicator (above 1.05)
- macrocytosis (belongs to the group of macrocytic anemias)
- basophilic puncture of erythrocytes, the presence of Joll's bodies and Kebot's rings
- the appearance of orthochromic megaloblasts
- decrease in reticulocytes
- leukopenia
- thrombocytopenia
- decrease in monocytes
- aneosinphilia

2. In stained smears - a typical picture: along with characteristic oval macrocytes, erythrocytes are found normal size, microcytes and schizocytes - poikilo- and anisocytosis.

3. The level of bilirubin in serum is increased due to the indirect fraction

4. Mandatory bone marrow puncture, since such a picture on the periphery can be in leukemia, hemolytic anemia, aplastic and hypoplastic conditions (however, it should be noted that hyperchromia is characteristic of B12-deficiency anemia). Bone marrow is cellular, the number of nucleated erythroid elements is increased 2-3 times against the norm, but erythropoiesis is ineffective, as evidenced by a decrease in the number of reticulocytes and erythrocytes in the periphery and a shortening of their life span (normally, an erythrocyte lives 120-140 days). Find typical megaloblasts - the main criterion for the diagnosis of B12-deficiency anemia. These are cells with "nuclear-cytoplasmic dissociation" (with a mature hemoglobinized cytoplasm, a delicate, reticular nucleus with nucleoli); large granulocytic cells and giant megakaryocytes are also found.

Treatment for B12-deficiency anemia:

Treatment for B12 deficiency (pernicious) anemia is to replace the missing vitamin. Since in this disease the absorption of vitamin B12 in the intestine is impaired, injections of this vitamin are prescribed. At first, injections are given daily or weekly for several weeks until the vitamin B12 level in the blood returns to normal; then injections are given once a month. People with this condition should receive vitamin B12 supplements for life.

B12-deficiency anemia (pernicious anemia, Addison-Birmer disease, malignant anemia) belongs to the group of megaloblastic anemias. The reason for the development of this condition is a lack of vitamin B12 (cyanocobalamin) in the body, as a result of which the process of hematopoiesis is disrupted.

The main causes of the onset of the disease

Vegetarianism can lead to a deficiency of cyanocobalamin in the body.

Deficiency of cyanocobalamin in the body can result from the influence of many endogenous and exogenous factors:

Symptoms of B12 deficiency anemia

External Clinical signs this type of anemia may not appear for a long time. Patients may complain of symptoms characteristic of many conditions and diseases, such as weakness, tinnitus, increased fatigue, decreased exercise tolerance.

Later, symptoms of the digestive system appear. Patients develop glossitis. Atrophy of the papillae of the tongue occurs, as a result, its surface is smoothed, becomes shiny ("varnished"), it acquires a bright red or even crimson color. This is one of the most specific features pernicious anemia. Development is also possible, patients may complain of, vomiting, change taste preferences, flatulence, or. In some cases, the spleen is also observed.

Simultaneously appear neurological symptoms, with a deficiency of cyanocobalamin, the peripheral nervous system primarily suffers. Patients feel weakness and numbness in the limbs, "creeping creeps", as a result of which fine motor skills, the gait becomes wobbly. With a further increase in vitamin B12 deficiency, disorders occur in the spinal cord and brain, patients may experience severe headaches, color perception is impaired, hallucinations and delusions may occur.

You can learn how to recognize a deficiency of vitamin B12 in the body from the popular TV show:

Pernicious anemia treatment

Before starting treatment, it is necessary to identify the cause of vitamin B12 deficiency, since one of the conditions successful treatment is the elimination of the factors that led to the development of anemia. In the presence of helminthic invasion it is necessary to contact an infectious disease specialist and conduct deworming. In cases where patients have structural changes in the digestive system or diseases in which absorption is impaired nutrients, you need treatment by a gastroenterologist.

Treatment of B12-deficiency anemia is carried out with the help of cyanocobalamin injections, most often the drug is injected intramuscularly. Pathogenetic therapy begins only after examination and confirmation of the diagnosis, since even one injection of a vitamin can affect the result of a blood test.

The therapy regimens are selected individually by the hematologist. In B12-deficiency anemia without damage to the nervous system, doses of cyanocobalamin up to 500 μg are used for treatment, usually injections are performed every other day or daily for 7-10 days. If the patient has neurological symptoms, higher doses of cyanocobalamin are used for treatment, daily dose can reach 1000 mcg. Then the administration of the drug continues in a maintenance dose once a week for a month. If further prevention of the development of B12-deficiency anemia is necessary, patients are given one injection of the vitamin once a month, the duration of treatment is determined by the doctor.

Diet plays an important role in restoring the body, patients need a full diet rich in vitamins, food that irritates the mucous membrane of the digestive system is excluded, and it is also necessary to completely abandon it.

Recovery normal performance blood flow occurs within several months, the condition of patients on the background of the therapy is improving rather quickly, but neurological symptoms can persist for up to six months.

Prevention of B12-deficiency anemia

The development of pernicious anemia in healthy people is possible only with an unbalanced diet or prolonged fasting, therefore, the most effective preventive measure is, rich in vitamins and other nutrients. The main source of vitamin B12 is food of animal origin:

• offal (beef, pork, chicken liver, heart, kidneys, etc.);
• fish, seafood;
• (beef, rabbit, lamb, pork, etc.);
• egg yolk;
• cheeses;
• dairy products.

Recent research shows that foods vegetable origin cyanocobalamin is not contained, in small quantities it can be obtained from yeast, yeast extract, etc. Therefore, strict vegetarians are advised to take vitamin supplements continuously or in courses to prevent pernicious anemia.

For people suffering from diseases in which the absorption of vitamins is impaired, it is possible to prescribe a permanent preventive therapy, once a month or less often, parenteral administration of a maintenance dose of the vitamin is performed. This will allow you to regularly replenish the reserves of cyanocobalamin in the body and prevent the development of anemia.

The identification and treatment of patients with diphyllobothriasis (a type of helminthiasis), as well as its prevention among workers in the fishing industry and people involved in food preparation, is also a means of preventing B12-deficiency anemia.

Catad_tema Iron-deficiency anemia- articles

Vitamin B12 deficiency anemia in children

ICD 10: D51

Year of approval (frequency of revision): 2016 (revised every 5 years)

ID: KR536

Professional associations:

• Public organization National Society of Pediatric Hematology
• oncologists
• FSBI "FNKTS DGOI them. Dmitry Rogachev "Ministry of Health of Russia
• NCC GOI
• Russian State Medical University named after Academician I.P. Pavlova.

Approved

Agreed

Scientific Council of the Ministry of Health Russian Federation __ __________201_

Vitamin B12

Bmtamin-B12 deficiency anemia

Terms and Definitions

1. Brief information

1.1 Definition

Anemia- a condition in which it decreases total amount hemoglobin in the body. A decrease in the concentration of hemoglobin in the blood is a key indicator as it can be measured directly.

1.2 Etiology and pathogenesis

The main reasons for the development of vitamin B12-deficiency anemia:

Decreased dietary intake of vitamin B12 (in infants whose mothers are vitamin B12 deficient, strict vegetarian diet)

Decreased absorption (deficiency of intrinsic Castle factor, gastric resection, malabsorption in the ileum due to diseases of the small intestine, bowel resection)

Increased intestinal loss (helminthic invasion, cecum syndrome)

Impaired transport of vitamin B12 from the intestine to tissue (hereditary transcobalamin deficiency)

Immerslund-Gresbeck syndrome is a combination of proteinuria with malabsorption of the vitamin B12 complex and intrinsic factor in the small intestine, a rare disease caused by gene mutation and debuting in early childhood.

Cyanocobalamin (vitamin B12) is found in foods of animal origin (meat, fish). The reserves of vitamin B12 in the body of an adult are about 5 mg, and if we consider that about 5 μg is lost per day, then the complete depletion of reserves in the absence of intake (malabsorption, vegetarian diet) occurs only after 3 years.

However, there are a number of reasons that can lead to the development of acute vitamin B12 deficiency anemia: 1) prolonged anesthesia with nitrous oxide, 2) severe diseases with massive transfusions, dialysis, complete parenteral nutrition.

Cyanocobalamin in the stomach binds to an intrinsic factor - a glycoprotein produced by the parietal cells of the stomach and other binding proteins present in saliva and gastric juice. These complexes protect cyanocobalamin from destruction during transport along the gastrointestinal tract. In the ileum, the complex of an intrinsic factor with cyanocobalamin binds to specific receptors on the surface of epithelial cells, the release of cyanocobalamin from intestinal epithelial cells and transport into tissues occurs with the help of special blood plasma proteins - transcobalamins. In cells, vitamin B12 is a cofactor of the methyltransferase catalytic reaction, which resynthesizes methionine and simultaneously regenerates 5-methyltetrahydrofolate to tetrahydrofolate and 5.10 methylenetetrahydrofolate.

Vitamin B12 deficiency can be caused by poor nutrition, impaired absorption (congenital or acquired deficiency of intrinsic factor, defect in the receptor for the vitamin B12 complex and intrinsic factor in the small intestine in Immerslund-Gresbeck syndrome, intestinal diseases) or metabolic disorders (congenital enzymatic pathology, transcobalamin deficiency, exposure to nitrous oxide).

Insufficient dietary intake of vitamin B12 is rare in children, although it can occur in infants whose mothers are themselves deficient in vitamin B12. Pernicious anemia, which is usually the cause of vitamin B12 deficiency in adults, is rare in children. The most common cause of vitamin B12 deficiency in children is malabsorption and congenital deficiency of carrier proteins.

1.3 Epidemiology

There are no data on the prevalence of vitamin B12 deficiency and vitamin B12 deficiency anemia in children in Russia.

1.4 Coding according to ICD-10

Vitamin B12 deficiency anemia (D51):

D51.0 - Vitamin B12 deficiency anemia due to intrinsic factor deficiency;
D52.1 - Vitamin B12 deficiency anemia due to selective malabsorption of vitamin B12 with proteinuria;
D52.2 - Deficiency of transcobalamin II;
D52.3 - Other dietary vitamin B12 deficiency anemias;
D51.8 - Other vitamin B12 deficiency anemias;
D51.9 - Unspecified vitamin B12 deficiency anemia.

2. Diagnostics

2.1 Complaints and anamnesis

It is recommended to find out the nature of the patient's diet. In the case of infants, the mother's diet should be clarified, how she ate before pregnancy, during pregnancy and during breastfeeding.

Children who do not have enough vitamin B12 in their diet are more likely to have deficiencies in other nutrients (including folic acid, iron).

It is necessary to pay attention to the possible manifestations of malabsorption syndrome. Find out the history of gastric resection, resection of the small intestine with the formation of cecum syndrome. It is necessary to exclude infestation by a wide tapeworm. Exclude Crohn's Disease and Other Causes chronic inflammation in the ileum.

An inherited absence or deficiency of carrier proteins is an important cause of vitamin B12 deficiency. A detailed family history should be collected. This pathology often makes its debut in early childhood and, if untreated, can cause not only anemia, but also myelopathy and developmental delay.

Urinalysis is necessary to exclude proteinuria as a manifestation of the Imerslund-Gräsbeck syndrome.

The clinic for vitamin B12 deficiency is characterized by a triad:
- blood damage;
- damage to the gastrointestinal tract;
- damage to the nervous system.

Anemia appears as weakness, fatigue, shortness of breath, palpitations. As a result of increased destruction of erythroid cells (ineffective erythropoiesis), moderate jaundice develops due to indirect bilirubin... The defeat of the gastrointestinal tract is manifested by anorexia, glossitis, "lacquered" tongue. Revealed a decrease in gastric secretion, atrophic gastritis. As a result of damage to the peripheral nervous system (funicular myelosis), ataxia, paresthesia, hyporeflexia, Babinsky's reflex appear, severe cases- clonus and coma. In children early age hypotrophy, growth retardation, irritability, chronic diarrhea, and a tendency to infections develop. If neurological symptoms are detected, their dynamics should be assessed during treatment.

2.2 Physical examination

General inspection involves an assessment of the overall physical condition, height and body weight. Pallor of the skin, mucous membranes is revealed, with severe anemia, there is a rapid heartbeat, shortness of breath.

Since with vitamin B12 deficiency anemia, ineffective erythropoiesis occurs in the bone marrow and, due to this, increased destruction of hemoglobin-containing cells, the level of indirect bilirubin in the blood rises and a slight yellowness of the sclera and skin appears. At severe forms there may be a slight enlargement of the spleen (reactive hyperplasia).

The examination reveals the above-mentioned pathology of the gastrointestinal tract (glossitis, atrophic gastritis) and neurological symptoms (funicular myelosis).

2.3 Laboratory diagnostics

Vitamin B12 deficiency anemia is characterized by:

-hyperchromia, macrocytosis;

- hypersegmentation of neutrophils;

-low level of reticulocytes;

-high level serum iron;

-high ferritin level;

-Moderate increase in indirect bilirubin;

- normal serum folate level (more than 3 ng / ml);

- normal level of folate in erythrocytes;

- low level of vitamin B12 in the blood (less than 100 pg / ml);

-picture of megaloblastic hematopoiesis in the bone marrow.

• Complete blood count with blood smear microscopy recommended

Comments: With a combination of iron deficiency and vitamin B12, a combination of laboratory signs can be observed, which leads to an uncertain picture and difficulty in diagnosis; in this case, you need to focus on clinical symptoms and anamnesis.

High reticulocytosis can be a sign of ongoing bleeding, hemolysis, and is also observed with vitamin B12 deficiency anemia a week after the appointment of vitamin B12.

Along with anemia, as a rule, there is a moderate decrease in the level of platelets and leukocytes.

In the presence of two- or three-growth cytopenia, it is necessary to consider the need for bone marrow examination to exclude leukemia, myelodysplastic syndrome, aplastic anemia.

The characteristic signs of megaloblastic hematopoiesis in the bone marrow disappear a few hours after the injection of vitamin B12.

• A biochemical blood test is recommended.

Evidence level 1 (level of evidence of recommendation B)

• A study of the level of serum iron, ferritin, folic acid and vitamin B12 in the blood is recommended.

Evidence level 3 (level of evidence of recommendation C)

• It is recommended to conduct a study of the absorption of Vitamin B12 in the intestine

Evidence level 4 (level of recommendation D)

Comments: Impaired intestinal absorption of vitamin B12 can be diagnosed using the Schilling test with radioactive labeled vitamin B12. Given the unavailability of labeled vitamin B12 in general laboratory practice, a modified Schilling test can be used: after ingestion of vitamin B12, the level of the vitamin in the blood is determined. The absence of an increase in vitamin B12 levels indicates a malabsorption of the vitamin in the intestine.

2.4 Differential diagnosis

Differential diagnosis is carried out with folate deficiency anemia, other forms of anemia with megaloblastoid type of hematopoiesis: congenital orotataciduria, Lesch-Nyhan syndrome, thiamine-dependent megaloblastic anemia, congenital dyserythropoietic anemia. In addition, it is necessary to exclude forms of anemia that occur with macrocytosis, but without signs of megaloblastoidity - aplastic anemia, autoimmune hemolytic anemia, liver disease, hypothyroidism, sideroblastic anemia.

Size needs to be estimated lymph nodes, liver, spleen, exclude the presence of formations in abdominal cavity, retroperitoneal space, other signs of malignant diseases.

3. Treatment

Indications for hospital treatment: severe anemia. In other cases, treatment is carried out on an outpatient basis.

• Vitamin B12 replacement therapy is recommended.

Evidence level 1 (level of evidence of recommendation A)

Comments: Vitamin B12 is prescribed at a dose of 5 mcg / kg per day for children under one year of age, 100-200 mcg per day for children after one year, 200-400 mcg per day for adolescents. The course of treatment is 4 weeks. Supportive therapy: weekly administration of the drug at the same dose for 2 months, then the next 6 months, the drug is administered 2 times a month. If it is impossible to eliminate the cause of the development of anemia, anti-relapse courses of treatment with vitamin B12 are carried out annually, for one course of 10-15 injections

In some patients, on the background of treatment with vitamin B12 and activation of erythropoiesis, iron deficiency may appear, which prevents the complete normalization of blood counts and requires standard treatment with iron preparations.

• With a decrease in the level of hemoglobin below 50 g / l, severe infections, cardiovascular disorders, transfusion of erythrocyte mass is recommended.

Evidence level 2 (level of evidence of recommendation B)

• It is recommended to monitor blood counts during treatment.

Evidence level 4 (level of recommendation D)

Comments:It is necessary to carry out a general blood test with the counting of reticulocytes, platelets, hematocrit - on the 7-10th day from the start of treatment. The presence of a reticulocytic reaction is important feature correct treatment. It is also necessary to monitor blood counts once a week. The normalization of the Hb level occurs after 4-6 weeks from the start of treatment and is a decisive confirmation of the correct diagnosis and treatment.

4. Rehabilitation

Specific rehabilitation activities for patients with vitamin B12 deficiency anemia, no. Dispensary observation is carried out taking into account the possibility or impossibility of eliminating the cause of vitamin B12 deficiency.

5. Prevention and dispensary observation

Primary prevention is a balanced diet, timely diagnosis and the treatment of helminthic invasions, the appointment of vitamin B12 in conditions leading to the development of its deficiency (for example, after resection of the intestine, subtotal resection of the stomach).

Criteria for assessing the quality of medical care

Quality criteria

Confidence level of evidence

Complete general (clinical) blood test completed

A biochemical (general therapeutic) blood test was performed

Therapy with vitamin B12 preparations was carried out

Bibliography

Pediatric Hematology / Edited by A.G. Rumyantseva, A.A. Maschan, E.V. Zhukovskaya. Moscow. Publishing group "GEOTAR Media" 2015 p. 656

Whitehead VM. Acquired and inherited disorders of cobalamin and folate in children. Br J Haematol... 2006 Jul. 134 (2): 125-36.

Duma A, Cartmill C, Blood J, Sharma A, Kharasch ED, Nagele P. The hematological effects of nitrous oxide anesthesia in pediatric patients. Anesth analg... 2015 Jun. 120 (6): 1325-30.

Dugu? B, Ismail E, Sequeira F, Thakkar J, Gr? Sbeck R. Urinary excretion of intrinsic factor and the receptor for its cobalamin complex in Gr? Sbeck-Imerslund patients: the disease may have subsets. J Pediatr Gastroenterol Nutr... 1999 Aug. 29 (2): 227-30

Trakadis YJ, Alfares A, Bodamer OA, et al. Update on transcobalamin deficiency: clinical presentation, treatment and outcome. J Inherit Metab Dis... 2014 May. 37 (3): 461-73

Appendix A1. Composition of the working group

Rumyantsev A.G. Doctor of Medical Sciences, Professor, Chief Pediatric Hematologist of the Ministry of Health of the Russian Federation, Director of the Federal Scientific and Clinical Center for Pediatric Hematology, Oncology and Immunology named after V.I. Dmitry Rogachev, Member of the Board of the Union of Pediatricians of Russia, Academician of the Russian Academy of Medical Sciences.

Maschan A.A.... Doctor of Medical Sciences, Deputy Director General of the Federal State Budgetary Institution FNKTS DGOI them. Dmitry Rogachev, Professor of the Department of Hematology, Oncology and radiation therapy Faculty of Pediatrics, Russian National Research Medical University named after N.I. Pirogova, President National Society pediatric hematologists and oncologists, member of the European Society of Hematology.

Demikhov Valery Grigorievich- Doctor of Medical Sciences, Professor, Director of the Scientific and Clinical Center for Hematology, Oncology and Immunology, Ryazan State medical University them. acad. I.P. Pavlova ”of the Russian Ministry of Health, a member of the NODGO, a member of the European Hematological Association (EHA).

Skobin V.B., Candidate of Medical Sciences, Hematologist of the Scientific and Clinical Center of Hematology, Oncology and Immunology, Ryazan State Medical University named after acad. I.P. Pavlova "of the Ministry of Health of Russia, a member of the NODGO.

Zhurina O.N., Ph.D., head. laboratory of the Scientific and Clinical Center of Hematology, Oncology and Immunology, Ryazan State Medical University named after acad. I.P. Pavlova "of the Ministry of Health of Russia, a member of the NODGO.

Conflict of interests absent.

Hematologists

Pediatricians

General practitioners

Table P1- Evidence confidence levels

Confidence level	Source of evidence
	Prospective randomized controlled trials Sufficient studies with sufficient power, involving a large number patients and receiving a large amount of data Large meta-analyzes At least one well-designed randomized controlled trial Representative sample of patients
	Prospective with randomization or no study with limited number data Several studies with a small number of patients Well-designed prospective cohort study Meta-analyzes are limited but good Results are not representative of the target population. Well-designed case-control studies
	Non-randomized controlled trials Insufficiently supervised studies Randomized clinical researches with at least 1 significant or at least 3 minor methodological errors Retrospective or observational studies Clinical observation series Conflicting data preventing a definitive recommendation
	Expert opinion / data from the report expert commission, experimentally confirmed and theoretically substantiated

Table P2- Levels of persuasiveness of recommendations

Credibility level	Description	Decryption
		First line method / therapy; or in combination with a standard technique / therapy
		Second line method / therapy; either in case of refusal, contraindication, or ineffectiveness of the standard technique / therapy. Monitoring of side effects is recommended
	there is no convincing evidence of either benefit or risk)	There is no objection to this method / therapy or no objection to the continuation of this method / therapy
	Lack of convincing Level I, II, or III publications showing significant benefit over risk, or convincing Level I, II, or III publications showing significant risk over benefit

Appendix A3. Related documents

• The procedure for rendering medical care population on the profile "hematology" (approved by order of the Ministry of Health of the Russian Federation dated November 15, 2012 No. 930n).

Appendix B. Patient management algorithms

Appendix B. Information for Patients

Lack of vitamin B12 can be observed in children with rare diseases: helminthic invasion by a wide tapeworm, with rare congenital diseases associated with a violation of the formation of the internal Castle factor (a protein responsible for the transfer of vitamin B12 from food to the blood), as well as immune disease, which is caused by the production of antibodies to an intrinsic factor. One of the reasons may be unhealthy diet, strict vegetarian diet. With a lack of vitamin B12 in the body, anemia develops, chronic gastritis, inflammation of the tongue (glossitis), neurological disorders appear. The disease is easily treatable with vitamin B12. A month after the start of treatment, the hemoglobin level normalizes. If the cause of vitamin B12 deficiency can be eliminated (worms, unhealthy diet), supportive treatment is not given. If the cause cannot be eliminated (the presence of antibodies to the intrinsic Castle factor, congenital absence of the intrinsic factor), the maintenance of vitamin B12 is carried out for life. Independent use of the drug is unacceptable. Your doctor should prescribe vitamin B12 taking into account all indications and contraindications.