Bone marrow is one of the most important organs responsible for hematopoietic functions. With its help, the production of vital blood components occurs, of which the most important are:

• leukocytes;
• platelets;
• red blood cells.

The names of the brain, symptoms and their diagnosis are presented below. But first you need to learn more about the components of blood.

Red blood cells

Red blood cells contain an important component called hemoglobin, which gives the blood its characteristic red color. The main purpose of red blood cells is to transport oxygen throughout the body. The brain is the most demanding for the constant delivery of new batches of oxygen, so its deficiency is felt first of all. This usually occurs when there are not enough red blood cells. Because of this, the person turns pale and begins to experience headaches.

Leukocytes

Another integral component of blood that is produced by the bone marrow are leukocytes. These are white blood cells that guard the body and repel attacks from pathogens that try to disrupt the normal functioning of the body. For this purpose, leukocytes produce special protective agents.

Platelets

The third group of blood cells are platelets, also called platelets. They make sure that when a scratch appears, the bleeding stops immediately. In this case, the blood becomes sticky, and the wound immediately heals from damage. It is important that the body does not lose a large amount of blood.

Therefore, even a slight disruption in its stable operation can lead to a slowdown and even stop of the production of new blood, and therefore appear serious problems in the functioning of the body.

Cells

Human bone marrow also contains unique stem cells that have the ability to transform into any cells necessary for the body. They are being very actively studied and attempts are being made to apply them in the latest methods of treating cancer.

There are two types of bone marrow cells:

• red, which consists of hematopoietic tissue;
• yellow, consisting of adipose tissue.

The generation of red cells occurs in the body during the embryonic development of the fetus. These cells appear in the second month in the collarbone and then form in the bones of the arms and legs. At approximately the fifth and a half month of child development, the bone marrow becomes a full-fledged organ

With age, a person gradually replaces red tissue with yellow tissue, which is accompanied by the aging process. The body loses its functions, resulting in various bone marrow diseases. Since the formation of new blood cells occurs in the bone marrow, there is a possibility of their mutations. Such cells are the cause of the appearance of malignant neoplasms.

Aplastic anemia

Aplastic anemia is a disease that is associated with the loss of the bone marrow's ability to produce the required amount of all major types of blood cells. The disease combines signs of anemia (insufficient number of red blood cells, low hemoglobin levels) and hematopoietic aplasia (inhibition of the production of all blood cells).

The main symptom of bone marrow disease in children and adults is constant weakness and apathy, lack of strength.

This is very rare disease: its frequency is about 2-6 cases per million inhabitants per year. It can occur at any age, but reaches its peak in young (15-30 years) and old (over 60 years) age.

Cancer

However, the truly terrible disease of the bone marrow is undoubtedly cancer. It has very confused and unclear symptoms, which make it quite difficult to detect it on early stages. And this is a vital action, since cancer is treatable only in the initial stages. The spread of painful metastases leads to painful death in 95% of cases. Therefore, you should pay attention to the signs of the disease as early as possible and consult a doctor. Such simple actions can save the patient’s life.

Causes of cancer

There are a huge number of reasons why a person can develop bone marrow disease. His lifestyle plays a rather important role, the presence stressful situations, poor health due to problems with the immune system and some health characteristics that are inherited. These include a predisposition to the occurrence of cancer.

Studies that have been carried out in last years, allowed us to come to the conclusion that, apart from other organs, the bone marrow is quite rarely affected. The most common cases are when the bone marrow is attacked by metastases.

Experts in the field of oncology report that metastases in the bone marrow most often occur in people with malignant tumors of the lungs, thyroid gland, mammary glands, and prostate glands. Metastases to the brain from malignant neoplasms in the colon occur only in 8% of cases. The spread of cells from the tumor site occurs with the help of blood, which delivers cancer cells to the bone marrow.

In very rare cases, primary cancer of this organ occurs. Scientists have not yet reached a consensus on the cause of its appearance. Reasons such as infections, malicious chemical substances or other negative impacts environment may play a significant role in its occurrence, but there is no convincing evidence of this.

Symptoms of cancer

The disease has a very characteristics:

• Severe weakness, rapid fatigue.
• Constant drowsiness and headaches.
• Pain in the intestines, accompanied by diarrhea.
• Constant vomiting.
• Severe pain in muscles and bones.
• Increased fragility bone tissue.
• Tendency to infectious diseases.

Although these symptoms of bone marrow disease in adults are not a 100% way to determine bone marrow disease, they are a strong signal to contact a highly qualified specialist for advice.

Diagnostics

The most effective test for bone marrow disease is a blood test, which can detect cancer in the early stages of development. Quite often, the disease is detected during routine medical procedures, such as a routine ultrasound. As a rule, it reveals existing cancer, which has already reached the third stage, since metastases have spread in large numbers in the patient’s organs and have dealt a blow to their stable functioning.

Typically, such stages of the disease cannot be successfully treated; you can only slow down the process a little and drown out the increasing pain with the help of medications.

Additional Methods

Among all diagnostic methods, it is worth highlighting the following:

1. By far the most effective way diagnosis is a routine blood test for bone marrow disease. This study allows you to diagnose the disease in its early stages, and do it very quickly. This will help to begin the treatment process immediately, which will significantly increase the patient’s chances of recovery.
2. A bone marrow puncture is a tissue removal procedure performed using a special technique. Despite the fact that this is a rather painful procedure for the patient, it must be performed to confirm suspicions of the presence of the disease. The puncture procedure involves using a special syringe to extract the contents of the bones through a puncture in the chest.
3. The only way Diagnosis and assessment of the degree of development of such dangerous pathologies as lymphoma and leukemia is a bone marrow biopsy. It also helps evaluate effectiveness drug therapy.
4. Scintigraphy is a test using radioisotopes that can detect the presence of bone tumors.
5. The use of magnetic resonance imaging will help to obtain a complete picture of the disease, to determine the size and location of cancer formations in the body.
6. Another modern diagnostic method is computed tomography, which can easily identify various pathologies.

Only a doctor can choose the optimal research method; for this, he analyzes existing symptoms.

Treatment method

Treatment of bone marrow diseases is a very long, painful and expensive task. To combat anemia, a large number of medications are used that have very serious side effects. The most radical treatment is a bone marrow transplant.

There are three main treatment methods for bone marrow cancer:

1. During chemotherapy, the patient takes a certain amount of special drugs that affect cancer cells, causing their death, and at the same time destroying metastases. Such drugs are usually prescribed in courses, the number of which is determined by the attending physician. They cause a large number of unpleasant side effects that greatly worsen the patient's condition.
2. Before preparing for a bone marrow transplant, radiation therapy is used, during which the patient's own diseased bone marrow is destroyed using large doses of radiation. In some cases, a bone marrow transplant is the only way to save a person. To do this, new bone marrow is taken from a donor, who is often a close relative. It is then placed into the patient’s body, where it must take root successfully. After a certain amount of time, new cells restore stable functioning of the body.
3. Unfortunately, this procedure can only help in the initial stages of cancer. At the third or fourth stage, successful treatment is impossible, but there are some ways that will help relieve pain and slightly prolong the patient’s life.

Transfer

Indications for transplantation are important for patients suffering from hematological, oncological or certain hereditary diseases. In addition, timely indications are important for patients with acute chronic leukemia, lymphomas, various types anemia, neuroblastomas and different types combined immunodeficiency.

Patients with leukemia or any type of immune deficiency have pluripotent SCs that do not function properly. In patients with leukemia, a huge number of cells begin to form in the blood that have not gone through all periods of development. In the case of aplastic anemia, the blood stops restoring the required number of cells. Degraded or immature and low-quality cells imperceptibly oversaturate the arteries and bone marrow, and over time spread to other organs.

In order to stop the growth and destroy harmful cells in diseases of the red bone marrow, extremely radical therapy is prescribed, such as chemotherapy or radiotherapy. Unfortunately, during these radical operations, both diseased cellular components and healthy ones die. And for this reason, the dead cells of the hematopoietic organ are replaced by healthy pluripotent SCs either from the patient himself or from a compatible donor.

You need to monitor your health, regularly visit specialists, and undergo a routine medical examination annually. At the first sign of bone marrow disease, you should immediately consult a doctor.

Aplastic anemia, caused by chemical and physical agents, is characterized by a direct relationship between the amount of toxic substance affecting the bone marrow and the intensity of the hypoplasia it develops (Munteanu, Rohr); the presence - in the clinical picture - of individual signs of damage to areas of the parenchyma of organs of great importance, such as the liver, kidneys, central nervous system, which is less often observed in other types of aplastic anemia.

TO toxic substances, which have a great effect on the bone marrow and are very well studied, include benzene, chloramphenicol and a number of other medications.

Below are substances, determining bone marrow hypoplasia and assessing the risk they pose.

Physical and chemical factors causing the development of aplastic anemia:
A. Factors, the presence of which in a certain amount, in any case contribute to the development of bone marrow aplasia, including ionizing radiation, mustard compounds (nitrogen mustard, etc.), cytostatic medications (antimetabolites, antifolic drugs), benzene, its compounds.

B. Factors that cause bone marrow aplasia only occasionally, including:
1. Antimicrobial:
Arsenicobenzenes
Chloramphenicol
Sulfamide
Streptomycin

2. Anticonvulsants:
Mesantoin
Trimethadione

3. Antithyroid: Methylthiouracil

4. Antihistamines: Phenergan

5. Insecticides: DDT

6. Various factors:
Gold salts
Phenylbutazone
Nitrophenol
Meprobamate

Benzene and its compounds as a cause of aplastic. Accidents caused by benzene began to be discovered at the beginning of this century, due to the industrial use of this substance as an organic solvent (Robr). In principle, benzene inhibits the bone marrow, which means stopping the synthesis of RNA in already differentiated elements.

Apparently benzene does not inhibit colony cells of the strain, which should be sought to explain the complete reversibility of disorders in cases of short duration of toxic effects (Nomiyama).

Influence at Bone marrow is closely related to the amount of substance affecting the patient. Initially, there is irritation of the bone marrow and general, in particular erythroid, hyperplasia, accompanied by leukocytosis, neutrophilia and a deviation to the left in the peripheral blood; then, gradually, bone marrow hypoplasia develops with extensive areas of fatty transformation, the presence of rare myeloid elements, a pronounced reaction of lymphatic or plasmacytic tissue, and in some cases a monocyte reaction, which is often difficult to distinguish from a leukemic process (Munteanu).

After development of bone marrow hypoplasia there is only a slim chance of its recovery. That is why attention is directed to the prevention of the disease by limiting the concentration of benzene in the ambient air of the relevant factories to a maximum of 34 parts per 1 million and identifying the first signs of bone marrow damage by monitoring the development of erythrocyte macrocytosis in workers of these factories (Munteanu).

However benzene has a number of other effects on the bone marrow, including causing: pronounced hyperplasia of the erythroid series and suspension of division (megaloblastosis), a picture called benzene erythropathy, which is very similar to acute erythemia; chronic myelosclerosis with myeloid metaplasia; hypoplasia of lymphatic tissue, as well as acute leukemia (Rohr, Wintrobe).

Chloramphenicol This is an antibiotic that aroused great enthusiasm in 1948, when its extraordinary effect was tested against diseases of typhoid fever, and then certain rickettsioses. But in the future wide application drug in the fight against infection with gram-negative pathogens has begun to reveal its harmful effects, since it contributes to the development of very severe irreversible bone marrow aplasia.

In the clinic, the risk of developing aplasia after treatment with chloramphenicol is 1/10 thousand-1/20 thousand. However, according to other statistics, for example, the Association of American Physicians, chloramphenicol accounted for the development of 44% of all pancytopenia diseases in the USA (Williams).

Formula chloramphenicol includes a benzene ring with a dichloroacetamide (Munteanu) side chain. In this regard, it was believed that the toxic effect should be attributed to the benzene nucleus. The validity of this assumption is also supported by the fact that, like benzene, the drug initially affects the erythroid series, stopping maturation, blocking the inclusion of iron in heme with a subsequent increase in serum iron levels, bone marrow sideroblasts and the development of reticulocytopenia.

Further studies revealed essentially simultaneous damage to all rows blood, while being the first morphological feature Bone marrow lesions turned out to be the appearance of vacuoles in bone marrow cells, which are better expressed in erythroblasts (Munteanu, Ward).

These data coincide with results of experimental observations, according to which the drug inhibits protein synthesis in bone marrow cells as a result of competition with ARNm (Ward), as well as RNA synthesis (Williams).

Later there were discovered quite severe complications some time after stopping treatment with this medication. In this regard, a hypothesis was put forward about the possible changes it causes in the genome of strain cells, resulting in irreversible shifts in the division mechanism of the latter, the development of irreversible bone marrow aplasia and acute leukemia (Mukherji) or nocturnal paroxysmal hemoglobinuria (Dachie and Lewis).

IN clinical practice It is advisable to remember that this medication causes severe, fatal aplasia and its use should be limited to diseases caused by pathogens that are strictly sensitive to it.

Others chemical agents leading to aplastic anemia. The category of other chemical factors that cause bone marrow aplasia includes DDT, sulfonamides, anticonvulsants, as well as gold compounds. It has also been proven that atebrine creates excessive sensitivity and thereby contributes to the development of bone marrow aplasia.

Nocturnal paroxysmal hemoglobinuria as a consequence of aplastic anemia. According to the results of a number of observations, nocturnal paroxysmal hemoglobinuria develops after bone marrow aplasia (Dacie and Lewis). Two cases of bone marrow aplasia accompanied by nocturnal paroxysmal hemoglobinuria and ultimately acute myeloblastic leukemia (“three-stage” evolution) have also been described (Holden and Lichtman).

It is stated that, at first, toxic agent affects (causes mutation) strain cells (Dacie and Lewis). The strain cells that survive give rise to abnormal populations: erythrocytes - sensitive to complement, granulocytes - lacking leukocyte alkaline phosphatase, and platelets lacking enzymes.

– inhibition of the hematopoietic function of the red bone marrow (erythrocytopoiesis, leukopoiesis and thrombocytopoiesis), leading to panhemocytopenia. The main clinical manifestations of hematological syndrome include dizziness, weakness, fainting, shortness of breath, tingling in the chest, skin hemorrhages, bleeding, and a tendency to develop infectious, inflammatory and purulent processes. The disease is diagnosed based on characteristic changes in the hemogram, myelogram and histological examination of trephine biopsy. Treatment of the pathology includes blood transfusions, immunosuppressive therapy, and myelotransplantation.

ICD-10

D61 Other aplastic anemias

General information

Aplastic (hypoplastic) anemia is a severe disorder of hematopoiesis (most often of all its components), accompanied by the development of anemic, hemorrhagic syndromes and infectious complications. Develops on average in 2 people per 1 million population per year. The pathology affects men and women with approximately the same frequency. Age-related peaks of incidence occur between the ages of 10–25 and over 50 years. With this pathology, the formation of all three types of blood cellular elements (erythrocytes, leukocytes and platelets) is often disrupted in the bone marrow, sometimes only erythrocytes alone; Depending on this, true and partial aplastic anemia are distinguished. In hematology, this type of anemia is one of the potentially fatal diseases, leading to the death of 2/3 of patients.

Causes

By origin, aplastic anemia can be congenital (associated with chromosomal aberrations) and acquired (developed during life). It is generally accepted that the inhibition of myelopoiesis is associated with the appearance in the red bone marrow and blood of cytotoxic T-lymphocytes that produce tumor necrosis factor and γ-interferon, which in turn suppress hematopoietic germs. This mechanism can be triggered by various external environmental factors (chemical compounds, physical phenomena, medicinal substances), as well as endogenous factors (viruses, autoimmune reactions). The most significant reasons include:

• Taking myelotoxic drugs. The connection between anemia and the use of certain antitumor, anticonvulsant, antibacterial, antithyroid, antimalarial drugs, tranquilizers, gold drugs, etc., which have a potential myelotoxic effect, has been reliably established. Drugs can cause both direct damage to hematopoietic stem cells and indirect damage through autoimmune reactions. Anemia associated with this development mechanism is called drug-induced.
• Contact with chemical and physical agents. Bone marrow suppression can be caused by interaction with organic solvents, arsenic compounds, benzene compounds, pesticides, and whole body irradiation. In some cases, hematopoietic failure is temporary and reversible - the main factors here are the concentration/dose of the substance and the time of contact. bone marrow suppression.
• Viral infections. From viral agents highest value is given to pathogens of hepatitis B, and. In this case, hypoplastic anemia usually develops within six months after viral hepatitis. When studying pathogenesis, it was noticed that virus replication occurs in mononuclear cells of the blood and bone marrow, as well as in immune cells. It is assumed that the suppression of myelopoiesis in this case is a kind of immune response that occurs against cells carrying viral antigens on their surface. This type of anemia is classified into a separate form - posthepatitis. Other viral infections include CMV, infectious mononucleosis, and influenza.

Cases of pancytopenia caused by infection with tuberculosis, intoxication, radiation sickness, lymphoproliferative diseases (thymoma, lymphoma, chronic lymphoblastic leukemia), and pregnancy have also been described. In almost half of the cases, the cause of anemia cannot be identified - such cases are classified as idiopathic.

Pathogenesis

Aplastic anemia may be based on either primary damage to hematopoietic stem cells or a violation of their effective differentiation. In hereditary anemias, hematopoietic failure is mediated by karyotypic aberrations, leading to impaired DNA repair and the impossibility of replication of bone marrow stem cells. In the case of acquired anemia, under the influence of etiofactors, activation of T cells is observed, which begin to produce cytokines (interferon-gamma, TNF) that affect hematopoietic precursor cells. In bone marrow stem cells, the expression of genes responsible for apoptosis and activation of cell death increases. The main clinical manifestations are caused by panhemocytopenia - a decrease in the composition of the blood of all its formed elements (erythrocytes, leukocytes, platelets).

Classification

In addition to various etiological options (drug, post-hepatitis, idiopathic), there are acute (up to 1 month), subacute (1 to 6 months) and chronic (more than 6 months) forms of the disease. Anemia that occurs with selective inhibition of erythropoiesis is called partial red cell aplasia. Based on the severity of thrombo- and granulocytopenia, this form of anemia is divided into 3 degrees of severity:

• very heavy(platelets less than 20.0x109/l; granulocytes less than 0.2x109/l)
• heavy(platelets less than 20.0x109/l; granulocytes less than 0.5x109/l), according to trepanobiopsy - low bone marrow cellularity (less than 30% of normal)
• moderate(platelets more than 20.0x109/l; granulocytes more than 0.5x109/l)

Symptoms of aplastic anemia

The defeat of three hematopoietic germs (erythro-, thrombocyto- and leukopoiesis) causes the development of anemic and hemorrhagic syndromes and infectious complications. The onset of aplastic anemia usually occurs acutely. Anemic syndrome is accompanied by general weakness and fatigue, pallor of the skin and visible mucous membranes, tinnitus, dizziness, tingling in the chest, shortness of breath on exertion.

Treatment of aplastic anemia

Patients with aplastic anemia are hospitalized in specialized departments. They are provided complete isolation and aseptic conditions to prevent possible infectious complications. Carrying out effective treatment is a complex problem in practical hematology. Depending on the level of cytopenia, the following treatment approaches are used:

• Immunosuppressive therapy. For moderate cytopenia, pharmacotherapy is prescribed, including a combination of antithymocyte immunoglobulin and cyclosporine A. Maintenance therapy is carried out with anabolic steroids or their combination with cyclosporines.
• Blood transfusions. In combination with a course of immunosuppressive therapy for low red blood counts, replacement blood transfusion therapy (transfusion of platelets and red blood cells) is indicated. This measure does not affect the pathogenetic link of the disease, but makes it possible to compensate for the deficiency of blood cells not produced by the bone marrow.
• Transplantation of BM and SC. The most favorable prognosis for long-term survival is provided by allogeneic bone marrow transplantation. However, due to the difficulty of selecting an immunologically compatible donor, the procedure is used to a limited extent. Autologous transplantations and peripheral blood stem cell transplantation are considered as experimental approaches. In patients with mild anemia, splenectomy and endovascular occlusion of the splenic artery may be indicated.

Prognosis and prevention

The prognosis is determined by the etiological form, severity and severity of anemia. Criteria for an unfavorable outcome include rapid progression of the disease, severe hemorrhagic syndrome and infectious complications. After bone marrow transplantation, remission can be achieved in 75–90% of patients. Primary prevention of this type of anemia involves eliminating the influence of unfavorable environmental factors, unjustified use of medications, preventing infectious diseases, etc. Patients with an already developed disease require clinical observation by a hematologist, systematic examination and long-term maintenance therapy.

Aplastic anemia is a severe hematological disease accompanied by anemia, a sharp decrease in immunity, as well as disorders of blood clotting processes. It occurs due to suppression of the hematopoietic function of the bone marrow (or bone marrow aplasia).

The disease was first described by the famous German doctor and scientist Paul Ehrlich, in 1888. A previously unknown pathology discovered in a young pregnant woman was accompanied by severe anemia, a decrease in the number of leukocytes, fever, bleeding and quickly led to the death of the patient. A postmortem examination revealed replacement of red bone marrow with adipose tissue. Later, in 1907, Anatole Chauffard, a French physician, proposed calling this disease aplastic anemia.

Aplastic anemia is a fairly rare disease. The average incidence is 3-5 per 1 million of the total population per year. Most patients are children and young people.

Types of aplastic anemia

There are hereditary (genetically determined) and acquired aplastic anemia.

80% of cases of the disease are caused by an acquired form of the pathology, 20% are caused by genetic factors.

Doctors use the classification of pathology according to ICD-10 ( International Classification Diseases 10 revision). The following types of aplastic anemia are distinguished:

D61.0 Constitutional aplastic anemia

D61.1 Drug-induced aplastic anemia

D61.2 Aplastic anemia caused by other external agents

D61.3 Idiopathic aplastic anemia

D61.8 Other specified aplastic anemias

D61.9 Aplastic anemia, unspecified

Aplastic anemia in children

In children, in most cases, the disease is acquired. The incidence rate is 2-3 cases per 1 million children (the peak incidence occurs in adolescence). In 70% of cases, the direct cause of the disease cannot be determined; it is generally accepted that viral infections, chemicals and medications.

Most often, the diagnosis is made accidentally, during a general blood test. With proper treatment and timely diagnosis, the prognosis is favorable. Aplastic anemia in children is well treated. The results of bone marrow transplantation and immunosuppressive therapy are approximately equal in effectiveness, but preference should be given to bone marrow transplantation from a suitable (ideally sibling) donor. Modern methods Treatment of aplastic anemia in childhood allows you to maintain health and does not affect the ability to have children in the future.

Causes and risk factors for aplastic anemia

Genetically determined disorders of hematopoietic function are noted in some hereditary pathologies, such as familial Fanconi anemia, Shwachman-Diamond syndrome, true erythrocyte aplasia, and congenital dyskeratosis.

Mutations in critical genes responsible for cell cycle regulation, protein synthesis, protection and repair of DNA damage lead to the formation of defective stem (hematopoietic) cells. Errors in the genetic code trigger apoptosis, a mechanism of programmed cell death. At the same time, the pool of stem cells decreases much faster than in healthy people.

The acquired form of pathology occurs as a result of direct toxic effects on hematopoietic cells. These factors include:

· Exposure to ionizing radiation. Maria Sklodowska-Curie, physicist and two-time laureate, died of aplastic anemia Nobel Prize, received for work in the field of radioactivity research and for the discovery of new radioactive elements;

· Pesticides, insecticides, benzene derivatives, heavy metal salts, arsenic have a direct toxic effect on the bone marrow, inhibit the production of blood cells and lead to the death of stem cells;

· Some medications have a similar effect. Nonsteroidal anti-inflammatory drugs, antitumor drugs, analgin, chloramphenicol (causes the most severe form of the disease, which, according to statistics, occurs in 1 out of 30 thousand courses of treatment with chloramphenicol), Mercazolil, carbamazepine, quinine can cause aplastic anemia in some people;

· The triggering factor for the disease can be viruses. Viral hepatitis, some types of parvoviruses, CMV, Epstein-Barr virus and HIV have the ability to cause a malfunction in the immune system, as a result of which it begins to attack the body’s own tissues. For example, in 2% of patients with acute viral hepatitis, aplastic anemia is detected;

· Autoimmune diseases (rheumatoid arthritis, SLE) can also be accompanied by bone marrow aplasia;

· Aplastic anemia during pregnancy is also believed to occur due to disturbances in the immune system.

In more than 50% of cases, the direct cause of the disease is not found, then they speak of idiopathic aplastic anemia.

What happens with aplastic anemia

Red bone marrow is the main and most important hematopoietic organ in which the formation and maturation of blood elements occurs. Hematopoietic stem cells in it give rise to red blood cells (responsible for the transfer of O 2 and CO 2 ), leukocytes (provide immunity) and platelets (participate in blood clotting processes). The number of hematopoietic cells is limited and gradually decreases throughout a person’s life.

With aplastic anemia, massive death of bone marrow stem cells occurs, and, as a result, a sharp decrease in the content of red blood cells, platelets and leukocytes in the patient’s bloodstream. A lack of red blood cells leads to anemia, a decrease in the number of leukocytes causes a sharp depression of the immune system, a decrease in the number of platelets is the cause of bleeding and, as a result, an increased risk of uncontrolled bleeding.

The results of recent studies give reason to believe that the acquired form of the disease is almost always an autoimmune pathology. The key point in the development of red bone marrow aplasia is the direct cytotoxic effect of T lymphocytes. However, the reason why T cells begin to recognize hematopoietic stem cells as targets for attack is still unknown. The triggering factor can be point mutations in the genes encoding human leukocyte antigens (HLA system), and explaining the distorted immune response (as in other autoimmune pathologies).

It is also believed that for the development of pathology, a combination of several factors is necessary - both internal (unknown defects in the DNA of stem cells, mutations of HLA genes, immune disorders) and external (drugs, viral infections, exotoxins and antigens).

How to suspect aplastic anemia - symptoms and signs of the disease

Symptoms characteristic of the disease:

· Unexplained weakness, fatigue, drowsiness;

· Low performance;

· Shortness of breath that occurs even with mild physical exertion;

· Dizziness, headaches;

· Interruptions in the heart, palpitations, tachycardia;

· Pale skin;

· Extension of blood clotting time, hemorrhages in soft tissues, the brain, the formation of bruises and bruises with minor exposure, nosebleeds, prolonged debilitating menstruation in women;

· Pinpoint hemorrhages in the skin and mucous membranes, bleeding gums;

Frequent infections ( respiratory tract, skin, mucous membranes, urinary tract), accompanied by fever;

· Painless ulcers on the oral mucosa;

· Weight loss, weight loss.

The course of the disease can be gradual or lightning fast (with the rapid development of extremely severe anemia, immunodeficiency, disorders of blood clotting processes with corresponding complications).

Diagnosis of aplastic anemia

For diagnosis, a detailed blood test and histological examination of material obtained from the bone marrow are used.

Laboratory signs of pathology detected in peripheral blood:

· Decrease in the concentration of red blood cells and hemoglobin in the blood without iron deficiency;

· Decrease in the concentration of leukocytes of all types in the patient’s blood;

· Platelet deficiency;

· Low number of reticulocytes - immature forms of red blood cells;

· Increased erythrocyte sedimentation rate (up to 40-60 mm/h).

In very severe cases, the hemoglobin concentration drops below 20-30 g/l. Color index, serum iron and erythropoietin levels are usually normal or elevated. The number of platelets is below normal, in severe cases they are completely absent.

The diagnosis is confirmed with a bone marrow biopsy. Histology of the punctate shows great content fat against the background of a decrease in the number of hematopoietic cells. Cellularity ( general content hematopoietic stem cells) - below 30%, megakaryocytes - platelet precursor cells - may be absent.

Severity of aplastic anemia

Based on the biopsy results, aplastic anemia is classified into mild, severe, and extremely severe aplastic anemia.

Severe form of the disease: cellularity - below 25%; in peripheral blood: neutrophils -< 0,5х10 9 /l, platelets -< 20х10 9 /l, reticulocytes -< 20х10 9 /l.

Extremely severe form of the disease: cellularity - below 25; in peripheral blood: neutrophils -< 0,2х10 9 /l, platelets -< 20х10 9 /l, reticulocytes -< 20х10 9 /l.

A mild form of pathology, deviations from the norm do not reach such critical indicators.

Treatment of aplastic anemia

Treatment tactics depend on several factors: the degree of severity, the age of the patient, the ability to undergo a bone marrow transplant from a suitable donor (ideally, close blood relatives of the patient).

The optimal treatment method for severe and extremely severe forms of pathology is considered to be bone marrow transplantation from a suitable donor. The maximum effect is observed in young patients. With a bone marrow transplant from a suitable donor, the 10-year survival rate can reach 85-90%.

If there are contraindications to bone marrow transplantation or it is not possible to perform it (lack of a suitable donor), immunosuppressive therapy is used.

The main drugs used for conservative therapy are antithymocyte immunoglobulin (ATG) and cyclosporine A.

ATG is a serum containing antibodies against human T lymphocytes obtained from horse blood. Administration leads to a reduction in the population of T-lymphocytes in the patient’s body, as a result of which the cytotoxic effect on stem cells is reduced and hematopoietic function is improved.

Cyclosporine A is a selective immunosuppressant that selectively blocks the activation of T lymphocytes and the release of interleukins, including interleukin-2. As a result, the autoimmune process that destroys stem cells is blocked, and hematopoietic function improves. Cyclosporine A does not suppress the hematopoietic function of the bone marrow and does not lead to total immunosuppression.

Indications for the use of glucocorticosteroids for aplastic anemia are limited to the prevention of complications during ATG therapy. In all other cases, steroid hormones have mediocre effectiveness and cause a number of complications.

Despite the high effectiveness of immunosuppressive therapy, the most radical treatment is a bone marrow transplant. The use of ATG and cyclosporine A increases the risk of developing myelodysplastic syndrome and leukemia and does not guarantee the absence of relapses of the disease.

If immunosuppressive therapy is ineffective, a bone marrow transplant is performed from a donor who is not related to the patient. The results of the operation may vary. In 28-94% of cases, 5-year survival is noted, in 10-40% of cases graft rejection occurs.

Patients with severe aplastic anemia receive blood products as emergency medical care. Red blood cell transfusion can quickly compensate for anemia, and platelet transfusion prevents life-threatening bleeding.

Correct lifestyle for aplastic anemia

Even with stable remission, it is necessary to undergo periodic examinations (primarily blood tests) and, if possible, to avoid exposure to negative factors.

During the treatment period, it should be remembered that patients with aplastic anemia have a weak immune system. It is necessary to avoid visiting crowded places, wash your hands regularly, and do not eat food prepared in questionable places (due to the risk of infection). Timely vaccination can prevent certain diseases (including influenza).

The high risk of bleeding or hemorrhage limits sports activities, especially traumatic ones. Despite this, an active lifestyle with regular dosed physical activity has a positive effect on the well-being and psycho-emotional state of patients.

A balanced diet rich in vitamins, minerals and proteins contributes to the rapid restoration of hematopoiesis. You should not eat perishable foods (due to the risk of foodborne illnesses). When treating with cyclosporine A, salt intake should be limited.

Complications of aplastic anemia

Opportunistic infections (viral, fungal, bacterial) caused by immunodeficiency;

Bleeding, hemorrhage, blood clotting disorders (caused by low platelet count);

Complications due to side effects medicines for the treatment of aplastic anemia (secondary hemochromatosis, serum sickness);

Transformation of the disease into myelodysplastic syndrome, leukemia and other hematological diseases.

Prognosis for aplastic anemia

Before the causes and mechanisms of development of the pathology were clarified, the mortality rate from aplastic anemia reached 90%. Over the past 20-30 years, the mortality rate of the disease has been significantly reduced. Modern treatment methods have significantly improved the prognosis - 85% of patients reach the 5-year survival threshold.

In children and young people, with adequate treatment, the prognosis is favorable and the five-year survival rate reaches 90% (for patients over 40 years old - 75%).

Prevention of aplastic anemia

There are currently no effective measures to prevent genetically determined aplastic anemia.

Prevention of acquired aplastic anemia involves adequate protection from exposure to toxic substances, pesticides and ionizing radiation. Self-administration of medications should be avoided, especially long-term and in high doses.

The following causes of acquired aplastic anemia are distinguished:

• ionizing radiation;
• medications ( decaris, analgin, chloramphenicol, tetracycline, butadione, etc.);
• chemical compounds ( pesticides, benzene);
• diseases ( viral hepatitis A, B and C, Epstein-Barr virus, cytomegalovirus, herpes virus, HIV, parvovirus B19, etc.).
• hormonal disorders from the ovaries, thyroid gland and thymus gland.

Some harmful agents directly affect the bone marrow ( ionizing radiation, chemicals and drugs). Others act indirectly through autoimmune mechanisms ( viral hepatitis B).

Mechanism of development of aplastic anemia

Today in scientific world There are several theories describing the mechanism of development of aplastic anemia. It is interesting that all theories are fully proven, and, nevertheless, cannot always explain bone marrow suppression in a particular case.

The following theories of the pathogenesis of aplastic anemia are distinguished:

• stromal;
• autoimmune;
• premature apoptosis.

Stromal theory

It has been proven that the growth and maturation of bone marrow cells is impossible without the influence of factors produced by the stroma. The stroma is a collection of connective tissue cells that form a kind of “skeleton” or “bed” in which bone marrow cells lie. The stroma produces substances such as IL ( interleukins) 1, 3 and 6 and stem cell factor. These substances direct the development of precursor cells in one direction or another at various stages of their development.

In 15–20% of cases of aplastic anemia, the cause of their development is insufficient formation and release of stromal growth factors. For this reason, the differentiation of blood cells stops at a certain stage of development. In the bone marrow, a special study can detect an accumulation of blood cell precursors. In the peripheral blood there is an increase in erythropoietin, which normally affects the bone marrow stroma.

Autoimmune theory

In bone marrow biopsies, in most cases, foci of accumulation of T-killer cells, monocytes, tumor necrosis factor alpha and gamma interferons are found, indicating an inflammatory mechanism for the development of aplastic anemia. A more detailed study of bone marrow sprout cells revealed the absence of a certain protein-carbohydrate complex encoded by the PIG-A gene on their surface. Mutation of this gene leads to the absence of synthesis of the above complex. As a result, the complement system, one of the links in the body’s immune defense, does not inactivate. As a result, the immune system perceives its own cells as foreign and seeks to destroy them. The larger the population of mutated cells in relation to healthy ones, the more pronounced the disorder in the synthesis of bone marrow cells.

Premature apoptosis theory

Apoptosis is a physiological process in which the independent destruction of cells with certain mutational anomalies or cells that have outlived their allotted time occurs. Through apoptosis, the body protects itself from the accumulation of mutations and the resulting complications, mainly of tumor origin. However, apoptosis can also become a pathological process when it leads to premature self-destruction of cells. The cause of premature apoptosis is a mutation in the gene that synthesizes the P-450 protein.

Despite the existence of several successful theories of the development of aplastic anemia, numerous studies in this direction are still being conducted in the scientific world. However, for a practicing physician, and even more so for a patient, searching for the mechanism by which the disease develops almost never makes sense. This is due to the fact that today there are no more or less effective drugs, in addition to steroid hormones, that can slow down the progression of anemia or at least partially compensate for it. Moreover, the most effective treatment today is bone marrow transplantation. Therefore, studying the mechanism of development of aplastic anemia is of exclusively scientific interest.

Symptoms of aplastic anemia

The classic symptoms of aplastic anemia fit into the following syndromes:

• anemic;
• hemorrhagic;
• toxic-infectious.

Anemic syndrome manifests itself:

• mixed shortness of breath, occurring with moderate and slight physical activity;
• increased fatigue;
• darkening and spots before the eyes;
• dizziness;
• the appearance of systolic anemic heart murmurs, etc.

Hemorrhagic syndrome manifests itself:

• slow stop of bleeding;
• frequent nosebleeds;
• heavy periods;
• skin bruising;
• thrombocytopenic purpura;
• easily formed bruises, etc.

Toxic-infectious syndrome manifests itself:

• weak immune status of the body;
• severe course mild viral diseases;
• slow wound healing;
• suppuration of scratches, etc.

Congenital forms of aplastic anemia deserve special attention, since they have some features that make it possible to suspect this disease at an early age and, if possible, influence its course.

Fanconi anemia

A rare congenital aplastic anemia with a severe course, diagnosed between the ages of 4 and 10 years. It affects males and females with equal frequency. It develops due to the high susceptibility of the DNA of body cells, and bone marrow in particular, to various types of mutations. Clinically manifested by the three syndromes listed above. The severity of the symptoms of the disease has a wave-like character with periods of remissions and exacerbations. There is a high risk of developing malignant tumor processes.

Up to 80% of patients are born with the following bodily abnormalities:

• From the musculoskeletal system - additional, missing or fused fingers, underdevelopment or absence of scapulae, non-fusion of the hard palate ( cleft palate, cleft lip), absence of ears, deformation of nasal cartilage, additional vertebrae, scoliosis, etc.
• From the outside nervous system - microencephaly or anencephaly, macrocephaly, spina bifida, blindness, deafness, myasthenia gravis, paraparesis and tetraparesis, mental retardation.
• From the genitourinary system - underdevelopment or absence of kidneys, accessory kidneys, renal polycystic disease, S-shaped kidney, horseshoe kidney ( fusion of one of the poles) ectopia of the ureters, exstrophy ( eversion) bladder, agenesis ( lack of development) uterus, bicornuate uterus, complete fusion of the hymen, anorchia ( absence of testicles), agenesis of the urethra and penis, etc.
• From the outside of cardio-vascular system - non-closure of the foramen ovale and interatrial septum, open batal duct, aortic stenosis at various levels, inversion of the great vessels of the heart, etc.
• From the digestive system - intestinal stenosis and aneurysms, diverticulosis, intestinal atresia ( blind-ending intestine), bronchoesophageal fistulas at various levels.

75% of patients have café au lait skin. There are also vitiligo - areas of skin with increased or decreased pigmentation. The only way to maintain the patient's life is to transfuse the missing blood components. For this reason, after 4 to 5 years of illness, the skin of patients acquires a grayish tint due to excess iron during the destruction of red blood cells. In cases where congenital anomalies are compatible with life, bone marrow transplantation is permitted as treatment. However, the prognosis of the disease is unfavorable. Most patients die at an average age of 7 years.

Diamond-Blackfan anemia

This type of anemia is considered partially plastic, since it is manifested by inhibition of exclusively the erythrocyte lineage of the bone marrow without involving the leukocyte and platelet lineages. The disease is familial and can occur if at least one parent has it. Since the disease is autosomal dominant, the probability of manifestation ranges from 50 to 100% depending on the combination of genes of the parents.

The immediate cause of the disease is the low sensitivity of bone marrow cells to erythropoietin. Clinically, only anemic syndrome is observed. A high probability of developing acute leukemia has been noted. In most cases, antibodies to erythrokaryocytes are detected, so immunosuppressive treatment is often effective. Maintenance treatment is carried out through regular red blood cell transfusions.

Diagnosis of aplastic anemia

The clinical picture of the disease can largely guide the doctor in the direction of anemia, but the diagnosis must be confirmed or refuted using laboratory tests and paraclinical studies.

The most valuable additional studies are:

• general blood analysis ( UAC);
• blood chemistry ( TANK);
• sternal puncture;
• trepanobiopsy.

General blood analysis

Data general analysis blood in aplastic anemia indicate pancytopenia ( reduction in the number of all three types of bone marrow cells). A decrease in the number of leukocytes is observed mainly due to a decrease in granulocytes ( neutrophils, eosinophils and basophils). Thus, the percentage of lymphocytes and monocytes in the leukocyte formula increases relatively. At various stages of the disease, inflammatory signs to one degree or another can be detected.

Indicative indicators of UAC for aplastic anemia are:

• Hemoglobin ( Hb) – less than 110 g/l ( norm 120 – 160 g/l). Reduction due to a decrease in the number of red blood cells.
• Red blood cells– 0.7 – 2.5 x 10 12 \l ( norm 3.7 x 10 12 \l). Decrease in the number of mature red blood cells.
• Reticulocytes- less than 0.2% ( norm 0.3 – 2.0%). Decrease in the number of young forms of red blood cells.
• Color index – 0,85 – 1,05 (norm 0.85 – 1.05) indicates the normochromic nature of anemia ( hemoglobin content in erythrocytes is within normal limits).
• Hematocrit ( Ht) – less than 30 ( the norm is 35 – 42 in women and 40 – 46 in men). The ratio of the cellular composition of blood to its liquid part. There is a clear decrease in the proportion of cells in the peripheral blood.
• Platelets– less than 35 ppm or 100 x 10 9 \l. Decreased platelet count.
• Leukocytes– 0.5 – 2.5 x 10 9 \l ( norm 4 – 9 x 10 9 \l). Severe leukopenia due to a decrease in the number of granulocytes ( neutrophils, eosinophils and basophils).
• Band neutrophils – 0 – 2% (norm less than 6%). Decreased production of young forms of leukocytes.
• Segmented neutrophils – 0 – 40% (norm 47 – 72%). Decrease in the number of mature forms of neutrophils.
• Myelocytes – 0 – 2% (normally absent). In conditions of granulocytopenia and bacterial infection, a more pronounced than usual shift in the leukocyte formula to the left is observed with the appearance of leukopoiesis precursor cells.
• Eosinophils – 0 – 1% (norm 1 – 5%). Decrease in the number of eosinophils.
• Basophils – 0% (norm 0 – 1%). Single or complete absence of basophils.
• Lymphocytes– more than 40% ( norm 19 – 37%). The number of lymphocytes remains normal. Due to a decrease in the granulocyte fraction, relative lymphocytosis is observed ( increase in the proportion of lymphocytes in the blood). Extremely pronounced lymphocytosis can be observed with the accumulation of viral infections.
• Monocytes– more than 8% ( norm 6 – 8%). The number of monocytes is unchanged and within normal limits. Monocytosis ( increase in the proportion of monocytes in the blood) is explained by a decrease in the percentage of granulocytes in the leukocyte formula.
• Erythrocyte sedimentation rate– more than 15 – 20 mm/hour ( the norm is up to 10 mm/hour in men and up to 15 mm/hour in women). This indicator reflects the severity of the inflammatory response in the body.
• Anisocytosis– the presence of red blood cells of various sizes in the blood.
• Poikilocytosis– the presence of red blood cells of various shapes in the blood.

Blood chemistry

Some types biochemical tests blood may focus the doctor’s attention on abnormalities in the body that indirectly fit into the three above-mentioned anemic syndromes.

Approximate indicators of BAC for aplastic anemia are:

• Serum iron more than 30 µmol\l ( norm 9 – 30 µmol/l). Increased serum iron levels due to frequent blood transfusions. High risk of developing hemochromatosis.
• Erythropoietin more than 30 IU/l ( norm is 8 – 30 IU/l in women and 9 – 28 IU/l in men). The increase in erythropoietin occurs for two reasons. Firstly, it is not consumed by the cells of the erythrocyte lineage. Secondly, its synthesis increases compensatoryly in response to anemia.
• НBs-AG and anti-HBcor immunoglobulins G– positive ( normal - negative). This analysis indicates the presence of viral hepatitis B. In some cases, this virus provokes the development of an autoimmune reaction against bone marrow cells.
• C-reactive protein – more than 10 – 15 mg\l ( norm 0 – 5 mg/l). It is detected during an inflammatory reaction against a background of weakened immunity.
• Thymol test– more than 4 ( norm 0 - 4). Detects signs of inflammation in weakened immune systems.

Sternal puncture

This type of study is used to visualize bone marrow cells and their percentage. The puncture is carried out in a treatment room using sterile instruments and painkillers, mainly inhalation. The puncture site is treated alternately with several antiseptic solutions. The patient is in a supine position. For puncture, special wide needles with an insertion depth limiter are used. The syringe and plunger must provide a sufficient level of compression, so it is preferable to use glass syringes with an iron plunger. Classically, the puncture is carried out in the body of the sternum at the level of 2 - 3 ribs with slow rotational movements until a sensation of failure is felt. A sharp perforation increases the risk of the needle slipping from the sternum and injury to the organs of the chest cavity. After the sensation of failure, the needle is fixed with one hand, and the syringe rod is tractioned with the other hand. The punctate is taken to the 0.3 - 0.5 mm mark, after which the needle is removed and the hole is sealed with an adhesive plaster. If there is no puncture at the puncture site, the puncture is repeated a few centimeters below. After the puncture, the patient should continue to remain in a horizontal position under the supervision of medical personnel for another 30 minutes.

After removing the syringe, it is emptied onto several glass slides, from which 10 to 15 smears will subsequently be made. Smears are fixed, stained and examined according to appropriate techniques. The result of the study is called a myelogram. The myelogram reflects the actual and relative cellular composition of the bone marrow.

With aplastic anemia, the myelogram will be scanty, the number of cellular elements is significantly reduced. Cambial cells of the erythrocyte and leukocyte series are single or absent. Megakaryoblasts are absent. In rare cases, during puncture it happens to encounter grouped foci of increased cell proliferation as a compensatory reaction of healthy bone marrow to anemia. Such a myelogram may be misleading because it will indicate the absence of aplastic anemia and will therefore be false negative.

Trephine biopsy

Trephine biopsy is a method of removing part of the bone marrow from the patient's ilium wing. The advantage of this procedure over sternal puncture is the possibility of collecting a larger amount of material while maintaining its structure. A larger amount of material reduces the likelihood of a false negative result of aplastic anemia, and the study of the structure of the bone marrow allows, in addition to cytological examination ( myelograms) also carry out histological examination.

During trepanobiopsy, the patient is in a prone position. The needles for this procedure are similar to the needles for sternal puncture, but larger in size. Anesthesia and the technique of collecting material are identical to those described above. The results of trepanobiopsy repeat the results of sternal puncture. In addition to this, an increase in the percentage of stroma in relation to hematopoietic cells is determined, as well as an increase in the proportion of yellow inactive bone marrow in relation to red active bone marrow.

Using a blood test and trepanobiopsy results, it is possible to determine the severity of aplastic anemia.

Aplastic anemia of moderate severity is determined by the following indicators:

• granulocytes less than 2.0 x 109\l;
• platelets less than 100 x 109\l;
• reticulocytes less than 2 – 3%;
• bone marrow hypoplasia on trephine biopsy.

Severe aplastic anemia is determined by the following indicators:

• granulocytes less than 0.5 x 109\l;
• platelets less than 20 x 109\l;
• reticulocytes less than 1%;

Extremely severe aplastic anemia is determined by the following indicators:

• granulocytes less than 0.2 x 109\l;
• platelets are single or absent;
• reticulocytes are single or absent;
• bone marrow aplasia on trephine biopsy.

Treatment of aplastic anemia with medications

Treatment of aplastic anemia is a complex and complex process. In the initial stages of the disease, various courses of therapy with glucocorticoid hormones and cytostatics are used to reduce the body's immune reactivity. In most cases, this approach gives temporary positive results, since the mechanism of development of aplastic anemia is largely associated with autoimmune reactions.

Medicines are an integral part of the treatment of aplastic anemia. The three most commonly used groups of drugs are immunosuppressants ( ), cytostatics ( cyclophosphamide, 6-mercaptopuryl, cyclosporine A, methotrexate, imuran, etc.) and antibiotics ( cephalosporins, macrolides, azalides, chloroquinolones, etc.). Less commonly, drugs can be used to correct blood pressure, disorders of intestinal microflora motility, enzyme preparations, etc.

Immunosuppressants can be used as monotherapy only in the initial stages of the disease and during the diagnostic process. Cytostatics for aplastic anemia can be used in combination with immunosuppressants. Another important purpose is to purify the stem cell concentrate from impurities of malignant cells. Antibiotics are used at all stages of the disease to treat concomitant infectious complications that occur against the background of weakened or even absent immunity.

Surgery for aplastic anemia

As pancytopenia progresses, the need for bone marrow transplantation arises - the only radical way to cure aplastic anemia. The problem is that a transplant requires a donor who will provide bone marrow that is compatible or at least partially antigenically compatible with the recipient’s bone marrow. Finding a donor can take a long time, which the patient does not have in most cases. In such cases, the patient is given transfusions of whole donor blood or its components in order to maintain a compensated state of his health.

In this section it is necessary to indicate that the operation, as such, is performed only on a bone marrow donor. The recipient does not undergo surgery. For decades, since the first bone marrow transplant in 1968, various methods of introducing stem cells into the patient's body have been studied. Of all the methods, intravenous administration turned out to be the most effective. It is for this reason that in the future, surgery for aplastic anemia will be called stem cell transplantation.

The following types of stem cell transplantation exist:

• allogeneic bone marrow transplantation;
• allogeneic transplantation of peripheral blood stem cells;
• autologous cord blood transplantation;
• autologous bone marrow transplantation;
• autologous transplantation of peripheral blood stem cells;
• syngeneic bone marrow transplantation.

Allogeneic bone marrow transplantation

This type of treatment involves extracting the donor's bone marrow and transplanting it into a sick recipient. Performing this procedure is a technically complex process and requires compliance with certain rules.

First of all, the donor must be compatible with the recipient’s body for three antigens in two HLA histocompatibility complexes. As a result, complete similarity of the donor and recipient in 6 antigens is expected. The minimum threshold at which transplantation can be carried out is a match of 4 out of 6 antigens, but in this case the risks of various kinds of complications increase several times. According to rough estimates, only in 30% of cases are donors found among the patient’s closest relatives who are fully compatible for all 6 antigens. Neither the age nor the gender of the donor matters. The youngest donor in the world was a four-month-old child weighing 3.6 kg.

Bone marrow extraction surgery is a modification of trepanobiopsy with some changes. First of all, this intervention is much more painful, so the use of general or epidural anesthesia is mandatory. The needles used have a large diameter. The puncture is performed 10 to 20 times into the crest of each ilium. The amount of material taken is much higher and amounts to 10–15 ml per kilogram of donor body weight. Thus, an amount of bone marrow equal to 700–1050 ml will be taken from a donor weighing 70 kg. Complications after such a procedure develop in less than 1% of cases. The vast majority of complications are associated with anesthesia and acute heart failure due to massive blood loss.

The resulting bone marrow is then slowly transfused into the recipient's body through intravenous access. However, such cases are quite rare, and more often the bone marrow is obtained from special storage banks of biological materials. These banks are replenished by donors around the world. Today, there are more than 50 national biological storage banks and more than 4 million donors around the world. Once the bone marrow is isolated, it must be stored for a long time. To do this, it is placed in a special solution that does not form ice crystals during freezing and thawing. The cooling rate is 3 degrees per minute. At a temperature of -85 degrees, stem cells are stored for 6 months. At a temperature of -196 degrees, stem cells are preserved for decades. If necessary, stem cells are thawed at a temperature of 44 - 45 degrees.

Before introducing a suspension of stem cells, they are treated with cytostatics in order to destroy the admixture of malignant cells. For a long period after transplantation, the patient must receive intensive immunosuppressive therapy to prevent transplant rejection and other unwanted immune reactions.

Allogeneic peripheral blood stem cell transplantation

Despite the fact that the most common method of obtaining stem cells from a donor’s body is the operation described above, in recent years the method of obtaining stem cells from peripheral blood has been actively studied. Its essence is to separate certain types of cells using a physical phenomenon called leukapheresis, followed by filtering the blood in special cell separators. IN in this case The source of stem cells is donor blood. After extraction, it is enriched with recombinant growth factors, which leads to an acceleration of the rate of stem cell division and an increase in their number.

This method has a number of advantages. Firstly, its side effects are the same as with regular blood donation. Secondly, the donor’s bone marrow is not affected, which must recover during the operation for at least six months. Thirdly, after transplantation of stem cells obtained in this way, adverse immune reactions are less likely to develop.

Autologous cord blood transplantation

In recent years, in some maternity hospitals, it has become possible to preserve umbilical cord blood extracted from the placenta immediately after childbirth and tying the baby’s umbilical cord. Such blood is extremely rich in stem cells. Cord blood is preserved in the same way as described above and stored for many years in biological storage banks. Blood is stored in case the owner develops blood diseases in the future, including aplastic anemia. Stem cells obtained from such blood do not cause transplant rejection and are readily available. The only drawback of such services is the high cost, since maintaining a safe deposit box in such a bank today is only possible for people with incomes much higher than the average level.

Autologous bone marrow transplantation

This method involves the removal of bone marrow from a patient before a blood disease or at the time of complete clinical remission for the purpose of its further use when the need arises. Bone marrow storage is carried out in a similar way. The conflict of incompatibility between donor and recipient stem cells is eliminated, since the donor and recipient are the same person.

Autologous peripheral blood stem cell transplantation

With this type of transplantation, the patient is transplanted with stem cells obtained from his own blood before the development of a blood disease. A conflict of antigenic incompatibility is also excluded.

Syngeneic bone marrow transplantation

Stem cell transplantation is performed from a donor who is homozygous ( identical) the patient's twin. The antigens on the surface of the cells of their organisms are identical, so such a transplant will not cause a rejection reaction and is equivalent to an autologous one.

After a stem cell transplant, the patient must be under the vigilant supervision of medical personnel. Active immunosuppressive therapy is mandatory. The patient's low immunity implies that he is in specialized sterile rooms with a closed ventilation system, bacterial filters, etc. Before entering the room, medical personnel must be dressed in sterile suits and go through a sanitary checkpoint.

Complications of bone marrow transplantation

Complications of bone marrow transplantation are divided into the following groups:

• infectious complications;
• graft-versus-host disease;
• transplant rejection reaction;
• failure of vital organs.

Infectious complications

The development of complications of this kind is typical for both the bone marrow donor and the patient to whom it is transplanted. Suppuration of a postoperative wound in donors develops quite rarely due to the small size of the puncture holes. However, if they are exposed to anaerobic bacteria, there is a risk of developing severe secondary osteomyelitis. Infectious complications in the bone marrow recipient occur due to intense immunosuppression carried out in order to successfully engraft stem cells. Against the background of decreased immunity, various bacterial infections occur, which must be treated with high doses of broad-spectrum antibiotics.

Graft-versus-host disease

The essence of this complication lies in the conflict between the immune cells of the host body and the newly formed immune cells of donor stem cells. In this case, donor lymphocytes show pronounced aggression towards the host lymphocytes. Clinically, this is manifested by a profuse rash, skin bullae, ulcers, dysfunction gastrointestinal tract, cardiovascular system, etc.

This complication develops exclusively when transplanting bone marrow or stem cells from an allogeneic donor. When transplanting one's own, previously frozen stem cells, this complication does not develop. This complication occurs when the bone marrow of the donor and recipient is fully compatible for all 6 antigens in 30% of cases. With partial compatibility, the risk of such a complication increases to 80%. To prevent this pathological reaction, cytostatics are used. The most common drug of choice is cyclosporine A paired with one of the following drugs - methotrexate, imuran or glucocorticoids ( dexamethasone, methylprednisolone, etc.)

Transplant rejection reaction

This complication develops when the immune system The host organism identifies donor stem cells as a threat and seeks to destroy them. This is typical when transplanting donor stem cells. When transplanting your own cells, this complication is eliminated. In patients with aplastic anemia, graft rejection develops in 20% of cases, that is, in every fifth patient. If this process is suspected, in addition to corticosteroids, recombinant growth factors are prescribed to increase the rate of tissue fusion.

Failure of vital organs

Bone marrow transplantation is a difficult test for all organs and systems of the body. High doses of medications, in particular cytostatics, have a destructive effect on the tissues of the liver, kidneys, endocrine glands, etc. When the protective reserves of organs are depleted, their functioning stops. The most common development is acute liver failure and renal failure. The drama of this complication lies in the fact that in most cases the only treatment method is a transplant of the affected organs from donors. But due to the fact that the cause of organ failure has not been eliminated, a healthy organ cannot be transplanted, since it is a short time will fail in the same way.

Prognosis for aplastic anemia

The prognosis for aplastic anemia largely depends on the timing of detection of the disease. With early detection, there is the possibility of more active intervention in the course of the disease. If detected later, the chances of cure decrease.

Congenital Fanconi aplastic anemia is in most cases extremely difficult to treat, since the bone marrow has never been healthy and, accordingly, is very difficult to recover. The presence of congenital developmental anomalies greatly limits the indications for bone marrow transplantation in such patients. In most cases, patients die in childhood from developmental abnormalities or infectious complications.

Acquired aplastic anemia has a more favorable prognosis, since in some cases it is reversible after the cessation of the action of the damaging factor on the bone marrow.

The use of methods for preserving umbilical cord blood, bone marrow stem cells and peripheral blood increases the chances of a complete recovery to 75 - 80%.