Relationship between PN and aplastic anemia. Paroxysmal nocturnal hemoglobinuria

Other name: pernicious anemia, B 12-deficiency anemia, megaloblastic anemia

A disease caused by impaired hematopoiesis due to a lack of vitamin B12 in the body.

Eye symptoms. The retina is pale or gray, retinal hemorrhages are possible, partial atrophy optic nerves. Central scotoma with a significant decrease in vision, which is quickly restored under the influence of vitamin B 12 therapy, and subicteric sclera are typical.

General manifestations. Characterized by symptoms of damage gastrointestinal tract, hematopoietic tissue and nervous system.

Weakness, shortness of breath, fatigue, and dyspeptic disorders appear. During exacerbation of the disease, pale skin with a lemon-yellow tint and Gunter's glossitis are characteristic, initially more pronounced inflammatory processes("scalded" tongue), subsequently - atrophic ("varnished" tongue). Inflammatory atrophic changes often spread to the mucous membrane of the gums, cheeks, pharynx, and esophagus.

The liver is enlarged, the spleen is dense. Patients are prone to obesity. Reveal gastric anomaly, while gastric juice does not contain intrinsic gastric factor Castle. Gastroscopy reveals nested or total atrophy of the gastric mucosa.

From the central nervous system, tabetic symptoms and symptoms of spinal paralysis are possible. Occurs frequently asthenic syndrome, at severe forms illness is sometimes observed hypochondriacal syndrome. At rapid development anemia leading to a lack of oxygen and cerebral ischemia, pernicious coma may occur with loss of consciousness, areflexia, collapse, hypothermia, shortness of breath, vomiting, and involuntary urination.

Hyperchromic anemia with a decrease in the number of red blood cells is noted in the blood. Characterized by an increase in red blood cells to 12-15 microns in diameter and their saturation with hemoglobin; color index is 1.4-1.8. The amount of vitamin B 12 in the blood is reduced.

Leading factor in the etiology of the disease- endogenous deficiency of vitamin B 12, resulting from a violation of its absorption due to a decrease or complete cessation of the production of the internal gastric factor Castle, necessary for the binding and adsorption of vitamin B 12.

Cases of familial diseases indicate the role of a genetic factor. Presumably the pathological gene is localized in the autosome and is characterized by incomplete dominance.

Differentiate with anemia due to deficiency folic acid, as well as due to vitamin B 12 deficiency of other origins.

The first description of the disease belongs to J. S. Combe (1822), who called it “severe primary anemia.” English doctor Th. Addison in 1855 described a disease called " idiopathic anemia", and the Swiss physician Anton Biermer (1827-1892) - in 1872 under the name "progressive pernicious anemia".

Etiology and pathogenesis. The development of Addison-Biermer anemia is associated with a deficiency of gastromucoprotein and, as a result, a violation of the absorption of vitamin B 12 administered with food. Due to cyanocobalamin deficiency, the conversion of folic acid into folinic acid is impaired, which interferes with the synthesis of nucleic acids. As a result, megaloblastic hematopoiesis develops and the function of the central and peripheral nervous system is disrupted (degenerative changes spinal cord-- funicular myelosis, demyelination nerve fibers and etc.). These disorders are based on severe atrophic changes in glandular epithelium stomach, the cause of which still remains unclear. There is an opinion about the meaning immune mechanisms, as evidenced by the presence in the blood serum of patients with Addison-Biermer anemia of antibodies against parietal cells of the stomach, and in the gastric juice - antibodies against gastromucoprotein.

It has been established that in the development of some forms of megaloblastic anemia play a role genetic factors. Described as autosomal recessive hereditary form AT 12 deficiency anemia in children, caused by the absence of gastromucoprotein in the gastric juice with normal secretion of hydrochloric acid and pepsin.

Clinic. Addison-Birmer anemia most often affects women aged 50-60 years. The disease begins gradually. Patients complain of weakness, fatigue, dizziness, headache, palpitations and shortness of breath when moving. In some patients in clinical picture Dyspeptic symptoms dominate (belching, nausea, burning at the tip of the tongue, diarrhea), less often - dysfunction of the nervous system (paresthesia, cold extremities, unsteadiness of gait).

Objectively - pale skin (with a lemon-yellow tint), yellowness of the sclera, puffiness of the face, sometimes swelling of the legs and feet and, which is almost natural, soreness of the sternum when beating. The patients' nutrition was preserved due to a decrease in fat metabolism. Body temperature during relapse rises to 38--39 °C.

Characteristic changes in the digestive system. The edges and tip of the tongue are usually bright red with fissures and aphthous changes (glossitis). Later, the papillae of the tongue atrophy, and it becomes smooth (“varnished”). Dyspeptic symptoms are caused by the development of achylia due to atrophy of the gastric mucosa. In half of the patients the liver is enlarged, in a fifth the spleen is enlarged.

Changes in the function of the circulatory organs are manifested by tachycardia, hypotension, heart enlargement, dullness of sounds, systolic murmur above the apex and above pulmonary trunk, "spinning top noise" over the jugular veins, and in severe cases - circulatory failure. As a result dystrophic changes in the myocardium, the ECG shows low wave voltage and lengthening of the ventricular complex; teeth ? decrease in all leads.

Changes in the nervous system occur in approximately 50% of cases. It is characterized by damage to the posterior and lateral columns of the spinal cord (funicular myelosis), manifested by paresthesia, hyporeflexia, impaired deep and pain sensitivity, and in severe cases, paraplegia and dysfunction of the pelvic organs.

A blood test reveals a high color index (1.2-1.5), pronounced macro- and anisocytosis with the presence of megalocytes and even single megaloblasts, as well as sharp poikilocytosis. Red blood cells with remnants of nuclei in the form of Cabot rings and Jolly bodies are often found. The number of reticulocytes is reduced in most cases. Leukopenia, neutropenia with hypersegmentation of neutrophilic granulocyte nuclei (6-8 segments instead of 8), and relative lymphocytosis are noted. A constant sign Addison's anemia - Birmer's anemia is also thrombocytopenia. The amount of bilirubin in the blood is usually increased due to its indirect fraction due to increased hemolysis of megaloblasts and megalocytes, the osmotic resistance of which is reduced.

In punctate bone marrow a sharp hyperplasia of the elements of erythropoiesis is detected, the appearance of megaloblasts, the number of which in severe cases reaches 60-80% in relation to all erythroblastic cells (see, color incl. Fig. II, p. 480). Along with this, there is a delay in the maturation of granulocytes and insufficient release of platelets.

The course of the disease is characterized by cyclicity. With severe anemia, a coma is possible. However, with the introduction to clinical practice liver preparations and especially cyanocobalamin, the course of the disease became more favorable, except in cases with symptoms of funicular myelosis, which causes early disability in patients. By using modern methods treatment can prevent relapses of the disease and provide the patient with practical recovery for many years. In this regard, the term " malignant anemia"makes no sense.

The diagnosis of Addison-Biermer anemia is not particularly difficult. Hyperchromic nature of anemia, megalocytosis, increased hemolysis, changes in the alimentary canal and nervous system, sternalgia, bone marrow puncture data are the most important diagnostic signs Addison-Birmer anemia.

Differential diagnosis is carried out with symptomatic forms of megaloblastic anemia. The latter are characterized by the presence of a basic pathological process (helminthic infestation, prolonged enteritis, agastria, etc.) and the absence of Addison-Birmer anemia typical clinical symptom complex damage to three systems: digestive, nervous and hematopoietic.

Serious difficulties can arise in differentiating Addison-Biermer anemia from symptomatic megaloblastic anemia that occurs with gastric cancer, as well as acute leukemia- erythromyelosis, accompanied by the appearance of peripheral blood megaloblastoid elements, which are essentially malignant leukemic cells, morphologically very similar to megaloblasts. The reference differential diagnostic criteria in such cases are the results of fluoroscopy of the stomach, gastroscopy and examination of bone marrow puncture (in acute erythromyelosis, blast cells are detected in the myelogram).

Treatment. An effective remedy treatment for Addison-Birmer anemia is cyanocobalamin, the action of which is aimed at converting promegaloblasts into erythroblasts, i.e., switching megaloblastic hematopoiesis to normoblastic. Cyanocobalamin is administered daily at a dose of 200-400 mcg subcutaneously or intramuscularly 1 time per day (in severe cases 2 times) until the onset of reticulocyte crisis, which usually occurs on the 4th-6th day from the start of treatment. Then the dose is reduced (200 mcg every other day) until hematological remission occurs. The course of treatment averages 3-4 weeks. Administration of folic acid for isolated cyanocobalamin deficiency is not indicated. For funicular myelosis single doses cyanocobalamin is increased to 1000 mcg daily for 10 days in combination with a 5% solution of pyridoxine hydrochloride and thiamine chloride (1 ml each), calcium pantothenate (0.05 g) and nicotinic acid(0.025 g) daily. For funicular myelosis, cobamide is effective, which should be administered 500-1000 mcg every other day along with the administration of cyanocobalamin.

With the development of coma, immediate transfusion of red blood cells (150-300 ml or whole blood (250-500 ml)) is indicated repeatedly (until the patient is removed from comatose state) in combination with loading doses cyanocobalamin (500 mcg 2 times a day).

Patients with Addison's anemia - Birmera in the period of remission should be registered at the dispensary. In order to prevent relapses, it is necessary to systematically administer cyanocobalamin (200-400 mcg 1-2 times a month). In case of intercurrent infection, mental trauma, surgical interventions, as well as in spring and autumn (when relapses of the disease become more frequent), cyanocobalamin is administered once a week. Patients are monitored through systematic blood testing. Periodic fluoroscopy of the stomach is necessary: sometimes the course of anemia is complicated by stomach cancer.

Basic blood functions such as oxygen transport and nutrients to tissues, removal of metabolic products, carried out thanks to red blood cells- erythrocytes. When the number of these cells in the blood decreases, a pathological condition develops - anemia. According to the mechanism of development of anemic syndrome, there are three main factors - large blood loss, destruction of red blood cells in autoimmune diseases, and a decrease in the production of red blood cells in the body.

Let's consider one of the infrequent forms of pathology that develops as a result of impaired blood formation - pernicious anemia.

Pernicious anemia - what is it?

Pernicious anemia, or Addison-Birmer disease, develops when the synthesis of red blood cells (erythrocytes) is impaired due to a lack of vitamin B12 in the body. Cobalamin (B12) deficiency occurs as a result of insufficient intake of this substance or the body's inability to absorb it.

This disease is characterized by a disruption in the maturation of red blood cells in the bone marrow; their synthesis is interrupted at the stage of megaloblasts - immature blood cells that are large in size and contain an increased amount of hemoglobin. Megaloblasts are unable to perform transport function blood and are soon destroyed as they pass through the spleen, causing body cells to experience oxygen starvation, as well as intoxication by products of its own decay.

In addition to the synthesis of red blood cells, cobalamin is involved in the oxidation of fatty acids and the utilization of their breakdown products, with in a deficit state this process stops and toxic substances accumulate in the body, destroying the sheath of nerve fibers. Addison-Beermer disease is the only anemia associated neurological symptoms and mental disorder.

Due to the large size of the cells, anemia is called megaloblastic, and increased content hemoglobin, which gives the cells a bright color, indicates hyperchromic pathology.

Manifestations of anemic syndrome were first described in 1855 by Thomas Addison, who was unable to find out the causes of the disease. A little later, the German doctor Anton Birmer studied the mechanism of development of anemia, giving it the name pernicious, which means “malignant”. In those days, malignant anemia was incurable disease, with time leading to irreversible changes in internal organs, nervous exhaustion and even to death. And only half a century later, a group of doctors made a discovery that was awarded Nobel Prize, they were able to cure anemia in dogs by adding raw liver to food, and later isolated a factor from the liver that eliminated anemia, which was called vitamin B12 or Castle's extrinsic factor.

The disease develops in 1% of older people age category. The risk group includes adolescents, athletes, and women with late pregnancy in need of increased quantity vitamin A. In children, pathology develops when hereditary predisposition to the disease, external factors can be serious malnutrition, as well as vegetarianism of the mother during the period of bearing the baby.

Causes of the disease and risk factors

Vitamin B12 is synthesized by a special strain of bacteria and can only be absorbed in lower section small intestine. In herbivores and some bird species, the intestinal microflora is populated by bacteria that produce cobalamin, which allows them to replenish the substance on their own. In the human body, such bacteria inhabit only the large intestine, so the vitamin B12 they synthesize is excreted along with the feces.

For this reason, a person can only obtain B12 from animal products, since plant foods contains its inactive analogue. Most cobalamin is found in the kidneys and liver, a little less in meat and seafood, dairy products and eggs contain small amounts of the vitamin, but if they are consumed regularly, a deficiency of this nutrient can be avoided.

Once in the stomach, vitamin B12 forms a bond with protein molecules (gastromucoprotein), which is synthesized by special cells gastric epithelium. This protein is commonly called intrinsic Castle factor; it protects cobalamin from the damaging effects of the acidic environment of the gastrointestinal tract. Protein breakdown - vitamin complex happens in small intestine, in its lower section, here the vitamin is absorbed by the mucous membrane and enters directly into the blood.

Pernicious anemia develops when one of the links that ensures the supply, absorption or storage of the vitamin in the human body is excluded. These may be the following factors:

Insufficient intake or complete absence in the diet of foods containing vitamin B12. Since cobalamin can accumulate in the liver and other organs, its reserves in the body are impressive; they can last for a couple of years, provided that animal products are completely avoided.
Helminthic infestations. Infection tapeworms, absorbing vitamin B12.
Disruption of the gastric epithelial cells responsible for the synthesis of gastromucoprotein, due to which the vitamin is destroyed without reaching the intestines. Factors contributing to the development of this pathology may include:
- taking medications that interfere with the fermentation of the stomach or changes in the cells of its mucous membrane;
- autoimmune diseases in which cells that produce internal Castle factor are degenerated;
- hereditary diseases, which are characterized by the absence of protective protein in the stomach or its slow synthesis;
- gastritis or;
- change in the acidity of gastric juice.
Acute and chronic intestinal diseases in which the absorption of vitamin B12 is impaired, such as:
- malignant neoplasms;
- partial removal of the small intestine;
- Crohn's disease;
- intestinal dysbiosis;
- Zollinger-Ellison syndrome.
Impaired storage of vitamin reserves in the liver when it is destroyed by cirrhosis.

Anemia can occur with increased consumption of the vitamin by the body during growth, significant strength loads, and multiple pregnancies. However, provided good nutrition and the absence of other factors that contribute to the aggravation of the pathology, B12-deficiency anemia can resolve itself.

What happens in the body when there is a lack of vitamin B12

Pernicious anemia has a gradual tendency to develop, manifesting itself first as an anemic syndrome, and then disrupting the functioning of the nervous system and internal organs.

Long before the appearance of neurological disorders and signs of megaloblastic anemia, the patient complains of weakness, drowsiness, severe headaches, loss of appetite, and dizziness. Such symptoms indicate oxygen starvation of cells caused by impaired transport of hemoglobin by red blood cells. A decrease in blood viscosity leads to changes in its pressure, which is expressed in arrhythmia and tachycardia.

Since immature red blood cells (megaloblasts) have a short lifespan, their death and breakdown of hemoglobin in the liver and spleen leads to an increase in these organs and disruption of the functioning of these organs.

Over time, the skin and sclera of the eyes may become jaundiced due to incomplete removal of bilirubin by the liver, and the tissues of the tongue, accumulating hemoglobin, become inflamed. A characteristic feature pernicious anemia is an enlarged tongue, scarlet in color with atrophied papillary epithelium, which is why the organ becomes smooth.

Progression of the disease leads to damage to the epithelium oral cavity and gastrointestinal tract, which is expressed in the following symptoms:

stomatitis and burning sensation of the tongue;
glossitis - inflammation of the tissues of the tongue;
feeling after eating;
chronic constipation;
pain in the intestines.

When fatty acid metabolism is disturbed, accumulation occurs toxic substances, destroying the fatty membrane of neurons in the brain and spinal cord. CNS lesions manifest themselves as follows:

memory loss;
disorientation;
absent-mindedness;
irritability.

The long-term course of B12 deficiency anemia syndrome can be manifested by behavioral disorders, inability to formulate and express thoughts, and memory loss. Since the ability to absorb the vitamin decreases with age, older people are most in need of additional sources of cyanocobalamin. The symptoms of Addison-Birmer disease are often confused with senile dementia, but the disease is so easy to cure.

With degenerative damage to the spinal cord, funicular myelosis occurs, which is characterized by the following symptoms:

numbness of the limbs, which is accompanied by tingling;
convulsions;
unsteady gait, stiffness and weakness in the legs;
loss of sensation in the feet.

On late stages manifestations of the disease can be:

urinary disturbance;
sexual dysfunction in men;
decreased hearing and vision;
mental disorders;
hallucinations;
paresis and paralysis;
amyotrophy.

Diagnosis and differential diagnosis

The diagnosis of pernicious anemia is made based on the following indications:

collection of patient complaints, from which the doctor can determine the duration of the disease;
a physical examination of the patient during which the doctor pays attention to changes in the epithelial covers of the tongue, skin tone, and decreased sensitivity of the extremities.
lab tests.

Mandatory laboratory research if B12 deficiency anemia is suspected, the following are:

Clinical blood test. With cyanocobalamin deficiency, red blood cells have an increased size, pronounced color, and uneven shape. The values of leukocytes, erythrocytes and platelets in the blood are reduced, while the values of lymphocytes exceed the norm.
Immunological analysis for the presence of antibodies to internal factor Castle.
Bone marrow analysis performed by puncture shows the megaloblastic type of hematopoiesis.
Urine and stool tests are necessary to determine the amount of vitamin B12 that is excreted from the body.
If the amount of cyanocobalamin is increased in the analysis, the Schilling test is performed to determine the cause of poor absorption of the substance.

Additional diagnostics can help determine the cause of anemia. Thus, gastroscopy allows you to determine the content of hydrochloric acid in the stomach, as well as the presence of antibodies that destroy stomach cells that synthesize protective protein. Additionally, a stool test is prescribed to check for the presence of helminthic infestations in the body. Studies of the stomach, intestines and liver are carried out if there is a suspicion of pathological diseases which led to the development of anemia.

When making a diagnosis, Addison-Biermer disease is differentiated from erythromyelosis and folate deficiency anemia.

Treatment of Addison-Birmer disease

Treatment of pernicious anemia is carried out under the supervision of such specialists as a hematologist, gastroenterologist, and neurologist.

The main therapy consists of replenishing the deficiency of vitamin B12 in the body by administering it subcutaneously. At the same time, the gastrointestinal tract is treated, the microflora is normalized, and, if necessary, helminthic infestation is eliminated. At autoimmune pathologies, simultaneously with drugs synthetic vitamin, glucocorticosteroids are administered to neutralize antibodies to intrinsic factor.

Drug treatment with drugs "Oxycobalamin" or "Cyanocobalamin", which are administered in the form subcutaneous injections, takes place in two stages - saturation and maintenance. During an exacerbation, the patient is administered the drug daily; the dosage and duration of the course depend on the age and severity of anemia. After vitamin B12 levels have returned to normal, maintenance therapy is carried out, which consists of administering the drug once every two weeks.

In parallel with this, diet therapy is used, which consists in correcting the patient’s diet. IN daily diet introduce foods rich in vitamin B12, such as beef, pork and chicken liver, seafood, mackerel, sardines, dairy products.

Deadlines full recovery hematopoiesis depend on the initial severity of anemia. Improvement occurs 2–3 months after the start of therapy.

Treatment prognosis and possible complications

At timely treatment the symptoms of the pathology are gradually eliminated, skin acquire a natural shade after 2 weeks, after the normal red blood cells are restored, digestive problems disappear, and stool returns to normal. Neurological disorders gradually smooth out, tissue sensitivity normalizes, gait is restored, neuropathy and memory loss disappear.

Unfortunately, when the stage is too advanced, atrophied optic nerves, as well as leg muscles, cannot be restored. Very in rare cases, after recovery, patients experience toxic goiter and myxedema.

If anemia occurs during pregnancy, vitamin B12 deficiency leads to placental abruption and premature birth. Insufficient oxygen supply to the fetus causes hypoxia (oxygen starvation), which affects the growth and development of the child.

In children with a hereditary vitamin B12 absorption disorder, anemia can manifest itself in enlarged internal organs (liver and spleen), decreased appetite, and developmental delays. The cause of cyanocobalamin deficiency in babies may be the mother's vegetarianism during breastfeeding.

Prevention

To prevent the development of the disease, you should properly organize your diet by including animal products rich in vitamin B12. Fatty foods should be limited, as it slows down the processes of hematopoiesis. You should also not abuse medications that inhibit the production of hydrochloric acid in gastric juice and can cause the destruction of the vitamin.

At chronic diseases stomach and liver, you should regularly undergo a blood test to check the vitamin content in the body.

People in old age you need to take vitamin B12 multivitamin complexes, or give injections medicinal product for preventive purposes.

Pernicious anemia - serious illness, which can lead to irreversible changes in the body and even disability. Before the discovery of vitamin B12 and Castle factor, the pathology was considered incurable and caused a slow decline ending fatal. Nowadays, the disease is very rare and occurs mainly due to impaired absorption of vitamin concomitant diseases Gastrointestinal tract. However, people who practice veganism ( veganism), as well as practitioners therapeutic fasting, put themselves at risk of developing B12 deficiency anemia.

My name is Elena. Medicine is my calling, but it so happened that I was unable to realize my desire to help people. But, I am the mother of three beautiful children, and writing articles on medical topics has become my hobby. I want to believe that my texts are understandable and useful to the reader.

Symptoms of Addison-Biermer anemia (disease)

Clinic

Addison-Birmer anemia most often affects women aged 50-60 years. The disease begins slowly and gradually. Patients complain of weakness, fatigue, dizziness, headache, palpitations and shortness of breath when moving. In some patients, the clinical picture is dominated by dyspeptic symptoms (belching, nausea, burning at the tip of the tongue, diarrhea), and less commonly, disorders of the nervous system (paresthesia, cold extremities, unsteadiness of gait).

Objectively, pale skin (with a lemon tint), slight yellowness of the sclera, puffiness of the face, sometimes swelling of the legs and feet and, almost naturally, soreness of the sternum when beating.

The patients' nutrition was preserved due to a decrease in fat metabolism. The temperature, usually low-grade, during a relapse rises to 38-39°C.

Characteristic changes in the digestive system. The edges and tip of the tongue are usually bright red with fissures and aphthous changes (glossitis). Later, the papillae of the tongue atrophy, causing it to become smooth and “varnished.” Due to atrophy of the gastric mucosa, achylia develops and, in connection with it, dyspepsia (less commonly, diarrhea). Half of the patients have an enlarged liver, and a fifth have an enlarged spleen.

Changes in the cardiovascular system are manifested by tachycardia, hypotension, heart enlargement, dullness of sounds, systolic murmur above the apex and above pulmonary artery, “spinning top noise” over the jugular veins, and in severe cases - circulatory failure. As a result of dystrophic changes in the myocardium, the ECG shows low wave voltage and lengthening of the ventricular complex; T waves in all leads decrease or become negative.

Changes in the nervous system occur in approximately 50% of cases and are characterized by damage to the posterior and lateral columns of the spinal cord (funicular myelosis), manifested by paresthesia, decreased tendon reflexes, impaired deep and pain sensitivity, and in severe cases, paraplegia and dysfunction of the pelvic organs.

From the blood side - a high color index (up to 1.2-1.3). This is explained by the fact that the number of red blood cells decreases to a greater extent than the hemoglobin content. At qualitative analysis A blood smear reveals pronounced macroanisocytosis with the presence of megalocytes and even single megaloblasts, as well as severe poikilocytosis. Red blood cells with remnants of nuclei are often found - in the form of Cabot rings and Jolly bodies. From the white blood side - leukopenia with hypersegmentation of neutrophil nuclei (up to 6-8 segments instead of 3). Thrombocytopenia is also a constant sign of Biermer's anemia. The amount of bilirubin in the blood is usually increased due to increased hemolysis of megaloblasts and megalocytes, the osmotic resistance of which is reduced.

ABSTRACT

ON THE TOPIC OF: Addison-Biermer anemia. Anemia in stomach cancer. Hypoplastic anemia

Addison-Birmer anemia

Etiology and pathogenesis. The development of Addison-Beermer anemia is associated with a deficiency of gastromucoprotein and, as a result, a violation of the absorption of vitamin B 12 administered with food. Due to cyanocobalamin deficiency, the conversion of folic acid into folinic acid is impaired, which interferes with the synthesis of nucleic acids. As a result, megaloblastic hematopoiesis develops and the function of the central and peripheral nervous systems is disrupted (degenerative changes in the spinal cord - funicular myelosis, demyelination of nerve fibers, etc.). These disorders are based on severe atrophic changes in the glandular epithelium of the stomach, the cause of which still remains unclear. There is an opinion about the importance of immune mechanisms, as evidenced by the presence in the blood serum of patients with Addison-Biermer anemia of antibodies against parietal cells of the stomach, and in gastric juice - antibodies against gastromucoprotein.

It has been established that genetic factors play a role in the development of some forms of megaloblastic anemia. An autosomal recessive hereditary form of B12 deficiency anemia in children has been described, caused by the absence of gastromucoprotein in the gastric juice with normal secretion of hydrochloric acid and pepsin.

Clinic. Addison-Birmer anemia most often affects women aged 50-60 years. The disease begins gradually. Patients complain of weakness, fatigue, dizziness, headache, palpitations and shortness of breath when moving. In some patients, the clinical picture is dominated by dyspeptic symptoms (belching, nausea, burning at the tip of the tongue, diarrhea), and less commonly, dysfunction of the nervous system (paresthesia, cold extremities, unsteadiness of gait).

Changes in the function of the circulatory organs are manifested by tachycardia, hypotension, enlarged heart, dullness of tones, systolic murmur over the apex and over the pulmonary trunk, “spinning top noise” over the jugular veins, and in severe cases - circulatory failure. As a result of dystrophic changes in the myocardium, the ECG shows low wave voltage and lengthening of the ventricular complex; teeth Τ decrease in all leads.

A blood test reveals a high color index (1.2-1.5), pronounced macro- and anisocytosis with the presence of megalocytes and even single megaloblasts, as well as sharp poikilocytosis. Red blood cells with remnants of nuclei in the form of Cabot rings and Jolly bodies are often found. The number of reticulocytes is reduced in most cases. Leukopenia, neutropenia with hypersegmentation of neutrophilic granulocyte nuclei (6-8 segments instead of 8), and relative lymphocytosis are noted. Thrombocytopenia is also a constant symptom of Addison-Biermer anemia. The amount of bilirubin in the blood is usually increased due to its indirect fraction due to increased hemolysis of megaloblasts and megalocytes, the osmotic resistance of which is reduced.

Bone marrow puncture reveals a sharp hyperplasia of the elements of erythropoiesis, the appearance of megaloblasts, the number of which in severe cases reaches 60-80% of all erythroblastic cells (see, color incl. Fig. II, p. 480). Along with this, there is a delay in the maturation of granulocytes and insufficient release of platelets.

The course of the disease is characterized by cyclicity. With severe anemia, a coma is possible. However, with the introduction of liver preparations and especially cyanocobalamin into clinical practice, the course of the disease became more favorable, except in cases with symptoms of funicular myelosis, which causes early disability in patients. With the help of modern treatment methods, it is possible to prevent relapses of the disease and provide the patient with practical recovery for many years. In this regard, the term “malignant anemia” is meaningless.

The diagnosis of Addison-Biermer anemia is not particularly difficult. The hyperchromic nature of anemia, megalocytosis, increased hemolysis, changes in the alimentary canal and nervous system, sternalgia, bone marrow puncture data are the most important diagnostic signs of Addison-Birmer anemia.

Differential diagnosis is carried out with symptomatic forms of megaloblastic anemia. The latter are characterized by the presence of a main pathological process (helminthic infestation, prolonged enteritis, agastria, etc.) and the absence of the clinical symptom complex typical of Addison-Biermer anemia affecting three systems: digestive, nervous and hematopoietic.

Serious difficulties may arise in differentiating Addison-Birmer anemia from symptomatic megaloblastic anemia that occurs in stomach cancer, as well as from acute leukemia - erythromyelosis, accompanied by the appearance in the peripheral blood of megaloblastoid elements, which are, in fact, malignant leukemic cells, morphologically very similar to megaloblasts. The reference differential diagnostic criteria in such cases are the results of fluoroscopy of the stomach, gastroscopy and examination of bone marrow puncture (in acute erythromyelosis, blast cells are detected in the myelogram).

Treatment. An effective treatment for Addison-Birmer anemia is cyanocobalamin, the action of which is aimed at converting promegaloblasts into erythroblasts, i.e., switching megaloblastic hematopoiesis to normoblastic. Cyanocobalamin is administered daily at a dose of 200-400 mcg subcutaneously or intramuscularly 1 time per day (in severe cases 2 times) until the onset of reticulocyte crisis, which usually occurs on the 4-6th day from the start of treatment. Then the dose is reduced (200 mcg every other day) until hematological remission occurs. The course of treatment averages 3-4 weeks. Administration of folic acid for isolated cyanocobalamin deficiency is not indicated. For funicular myelosis, single doses of cyanocobalamin are increased to 1000 mcg daily for 10 days in combination with a 5% solution of pyridoxine hydrochloride and thiamine chloride (1 ml each), calcium pantothenate (0.05 g) and nicotinic acid (0.025 g) daily. For funicular myelosis, cobamide is effective, which should be administered 500-1000 mcg every other day along with cyanocobalamin.

With the development of coma, immediate transfusion of red blood cells (150-300 ml or whole blood (250-500 ml)) is indicated repeatedly (until the patient is brought out of the coma) in combination with loading doses of cyanocobalamin (500 mcg 2 times a day).

Patients with Addison-Birmer anemia in the period of remission should be monitored at the dispensary. In order to prevent relapses, it is necessary to systematically administer cyanocobalamin (200-400 mcg 1 - 2 times a month). For intercurrent infection, mental trauma, surgical interventions, as well as in spring and autumn (when relapses of the disease become more frequent), cyanocobalamin is administered once a week. Patients are monitored through systematic blood testing. Periodic fluoroscopy of the stomach is necessary: sometimes the course of anemia is complicated by stomach cancer.

Anemia in stomach cancer

Megaloblastic anemia in gastric cancer develops as a result of tumor damage to the glands of the fundus of the stomach that produce gastromucoprotein, and is often accompanied by tumor metastases to the bone marrow. Megaloblastic anemia in gastric cancer differs from classical Addison-Biermer anemia the following signs: progressive weight loss, ineffectiveness of cyanocobalamin, mild severity of hyperchromic-megalocytic blood tingling, usually a predominance of erythroblasts (normocytes) over megalocytes, megaloblasts, frequent neutrophilic leukocytosis with a leukemoid shift, and in some cases - hyperthrombocytosis and, as a rule, the absence of signs of hyperhemolysis. Decisive diagnostic criterion are data from fluoroscopy of the stomach and examination of bone marrow puncture, in which cancer cells are often found.

Hypoplastic (aplastic) anemia

Hypo- and aplastic anemia is anemia with a continuously progressive course, developing as a result of deep inhibition of hematopoiesis.

Etiology. Hypoplaetic anemia occurs under the influence of various external factors, which include drugs: amidopyrine, cytostatic drugs (myelosan, chlorbutin, cytosar, dopan, thiophosphamide, benzoteph, mercaptopurine, etc.), antibiotics (chloramphenicol, streptomycin, etc.); chemical substances: benzene, gasoline, arsenic, heavy metals(mercury, zismuth); radiation energy (x-rays, radium, radioisotopes); infectious processes(sepsis, flu, viral hepatitis, some forms of tuberculosis). Genuine hypoplastic anemia is also distinguished.

The pathogenesis of hypoplastic anemia is associated with toxic effects pathogenic factors on bone marrow hematopoiesis, namely stem cell, the deficiency of which leads to disruption of the processes of proliferation and differentiation of all bone marrow sprouts. The possibility of changes at the level of stromal elements that make up the stem cell microenvironment, as well as suppression of hematopoiesis by immune lymphocytes, cannot be excluded.

Cytochemical and autoradiographic studies revealed various disorders metabolism of hematopoietic blood cells and, above all, the metabolism of nucleoproteins. Apparently, as a result of these disorders, hematopoietic cells cannot absorb various hematopoietic substances (cyanocobalamin, iron, hematopoietins), which are so necessary for their differentiation and proliferation. The level of these substances in the blood serum is increased in hypo- and aplastic anemia. There is also deposition of iron-containing pigment in various organs and tissues (liver, spleen, bone marrow, skin, etc.). The causes of hemosiderosis are impaired hemoglobin formation, inhibition of erythropoiesis and increased destruction of qualitatively defective red blood cells. It is also assumed that there is a possibility of a more intensive intake of iron into the cellular elements of organs and tissues due to disruption of metabolic processes in them. Frequent blood transfusions also play a role.

In the development of the disease, a decisive role, apparently, belongs to immune and endocrine-metabolic changes. There is evidence confirming the pathogenetic role of disruption of the functional state of the pituitary-adrenal system and spleen, which has a perverted, inhibitory effect on hematopoiesis.

Clinic. Hypoplastic (aplastic) anemia occurs mainly in young and middle age. The disease begins with the appearance general weakness, dizziness, headache, tinnitus. In some cases, there is an acute onset, characterized by general adynamia, bone pain, hemorrhagic manifestations (nasal, gingival, uterine, renal, gastrointestinal and other bleeding). In the pathogenesis of bleeding, disturbances in the blood coagulation system play a role, mainly in its first phase, towards hypocoagulation due to thrombocytopenia, as well as increased permeability and decreased resistance of the vascular wall.

There is a sharp pallor of the skin and mucous membranes with hemorrhages, and in the presence of a hemolytic component - jaundice. In most cases, changes in the circulatory system are observed: tachycardia, expansion of the boundaries of the heart, deafness of tones, systolic murmur above the apex and base of the heart, decrease blood pressure. Peripheral lymph nodes, liver and spleen are not enlarged. Body temperature is normal in most cases; its increase is usually associated with the addition of a secondary infection.

The blood picture is characterized by pancytopenia. Severe anemia (normochromic, aregenerative), leukopenia due to neutropenia and severe thrombocytopenia with the appearance of a number of positive tests(prolongation of bleeding time, positive tourniquet sign, weakening or absence of blood clot retraction). In partial hypoplastic anemia, the platelet count is normal.

When studying the bone marrow in hypoplastic anemia, a decrease in the total number of nuclear elements of the punctate is noted with a violation of their maturation by different stages development. With aplastic anemia, progressive depletion of the bone marrow develops - panmyelophthisis. Microscopically in this case, only single bone marrow elements are detected, among which lymphoid, plasmatic, fat cells and macrophages. In specimens obtained from trepanobiopsy, replacement of myeloid tissue with adipose tissue is observed.

Differential diagnosis is made with aleukemic leukemia. The results of sternum puncture and trepanobiopsy are of decisive diagnostic importance. ilium. In leukemia, leukemic metaplasia of the bone marrow is observed, and in hypoplastic anemia, it is devastated.

Hypoplastic anemia, occurring with hemorrhagic phenomena, often simulates Werlhof's disease. Differential diagnosis between them is carried out mainly on the basis of the nature of anemia and the picture of bone marrow hematopoiesis. If in Werlhof's disease the degree of anemia is adequate to the intensity of blood loss, then in hypoplastic anemia there is no such adequacy. Along with this, Werlhof's disease is characterized by an increased content of megakaryocytes in the bone marrow aspirate, while in hypoplastic anemia they are either absent or their content is sharply reduced and inhibition of other bone marrow sprouts is noted. Bone marrow examination also plays a leading role in differential diagnosis hypoplastic anemia occurring with a hemolytic component, with Marchiafava-Micheli disease.

Flow. By features clinical course The following variants of hypo- and aplastic anemia are distinguished: acute and subacute aplastic anemia, subacute and chronic hypoplastic anemia, chronic hypoplastic anemia with a hemolytic component and partial hypoplastic anemia with preserved thrombocytopoiesis.

The life expectancy of patients with hypoplastic anemia ranges from 2 to 10 years or more. Aplastic anemia has a high mortality rate. The cause of death is usually associated inflammatory processes or heart failure caused by severe anemia. There are also hemorrhages in the vital important organs(particularly in the brain).

One of the criteria for determining the prognosis of the disease can be a bone marrow colony formation test. With CFU values (colony-forming unit of bone marrow) above 20-10 5 nuclear cells the prognosis is favorable, more low performance indicate a poor prognosis (bone marrow aplasia). An unfavorable sign is also a decrease in the number of platelets below 10 17 l and neutrophil granulocytes below 0.2 G/l.

Treatment. IN complex therapy In hypoplastic anemia, blood transfusions play a dominant role. With pronounced hemorrhagic syndrome preference is given to repeated transfusions of freshly citrated blood or blood with short shelf life (up to 5 days), which retains hemostatic properties, in a single dose of 250-500 ml. For moderate bleeding, in order to obtain a mainly antianemic effect, it is better to use 150-300 ml of red blood cells. Transfusions of washed red blood cells are indicated for patients with a hemolytic component.

Blood transfusions are carried out 1-2 times a week, and more often if necessary. Leukocyte and platelet mass is prescribed when there is a sharp decrease in the number of leukocytes and platelets, the appearance of purulent-septic processes and severe bleeding.

In this case, one should remember about the possible sensitization of the recipient by antigens of introduced leukocytes and platelets, especially with repeated transfusions. Therefore, we must strive to select transfusion media taking into account HLA compatibility.

Hemotherapy should be combined with the introduction of a B complex of vitamins as regulators and stimulators of erythropoiesis.

Corticosteroids are widely used, especially in cases of severe bleeding and hemolytic syndrome, which are administered for 2-3 weeks in large doses (prednisolone-1 -1.5 mg/kg) followed by a transition to maintenance doses (15-20 mg). The duration of treatment with corticosteroids is strictly individual (from 3-4 weeks to 2-3 months) and depends on the course of the disease. Also used anabolic steroid(methandrostenolone - nerobol, retabolil, etc.) for 4-6-8 weeks; androgens (5% oil solution testosterone propionate 1 ml once a day) for several months. For hemostatic purposes, hemostatic and vascular strengthening agents are prescribed (ascorbic, aminocaproic acid, ascorutin, dicinone, calcium preparations, etc.). Due to the presence of hemosiderosis, desferal is prescribed 500 mg 1-2 times a day intramuscularly.

In case of ineffectiveness conservative therapy Donor (allogeneic) bone marrow transplantation and splenectomy are indicated; they are more effective in combination with each other. How to remove the spleen immune organ promotes better bone marrow engraftment. After the operation, the pathological influence of the spleen on hematopoiesis is removed, which explains positive effect splenectomy.

Thanks to complex therapy for hypoplastic anemia, it is now possible to achieve long-term remissions and reduce mortality. However, in case of aplastic anemia, the use of the above therapeutic measures ineffective.

Prevention of hypo- and aplastic anemia consists of strict adherence to occupational safety precautions associated with exposure to the body harmful factors (x-rays, benzene, etc.). Workers industrial enterprises, where there are certain occupational hazards that affect hematopoiesis (dyes, mercury vapor, gasoline, benzene, etc.), require systematic hematological monitoring at least twice a year. It is also necessary to limit uncontrolled use medicines, which have a cytopenic effect. During drug, X-ray and radiotherapy, systematic monitoring of blood composition should be carried out (at least once a week). Patients with hypoplastic anemia are subject to constant clinical observation.

References

1. Internal illnesses / Under. ed. prof. G.I. Burchinsky. - 4th ed., revised. and additional ― K.: Vishcha school. Head Publishing House, 2000. - 656 p.