Aplastic anemia concept of the cause, signs, diagnosis, treatment and prognosis

Aplastic anemia is a very complex disease, the treatment of which depends on its degree and severity

Treatment is usually aimed at eliminating the cause of the disease and its symptoms. However, idiopathic aplastic anemia is not known for its reasons, so a bone marrow transplant may be the only cardinal treatment method.

Methods of treatment for aplastic anemia:

  • Transfusion of erythromass. Transfusion of erythromass allows you to increase the level of hemoglobin in the blood, reduce the degree of oxygen starvation of organs and tissues, restore the blood composition of the patient. However, this is a temporary measure that can slow down the development of the disease, but not completely eliminate it.
  • Transfusion of thrombomass. Platelets play an important role in the body. With aplastic anemia, patients die most often due to bleeding and loss of blood, therefore, it is necessary to restore the balance of platelets in the blood. In this case, it is very important that the patient does not provoke bleeding. Women are prescribed drugs that inhibit ovulation in order to avoid menstrual bleeding, and all patients should be careful, avoid physical exertion and traumatic situations.
  • Drugs to protect against infection. The transfusion of the mass of leukocytes is impossible, as they circulate through the bloodstream for only a few hours, and then die and are updated. For this reason, such transfusions are useless. To protect a weakened body from infection, antibiotics, antiviral and antifungal drugs are often prescribed.
  • Immunosuppressants. These are drugs that inhibit the immune system. Usually they are prescribed after bone marrow transplantation so that the body does not reject a new organ. These drugs include cyclosporine.
  • Bone marrow transplantation. All of the above measures are temporary. The best way to prolong a patient’s life is to have a bone marrow transplant from a suitable donor. The closest relatives are the best donors, especially siblings. Unfortunately, even in the case of a successful operation, if the bone marrow has taken root, the average level of life extension is 5 years. After this period of time, a relapse of the disease often occurs. The younger the patient and donor, the higher the chances of a successful organ transplant.

It is very difficult to talk about the prognosis, since it all depends on the effectiveness of treatment and the individual characteristics of the body

Complications and prognosis directly depend on the severity of the patient’s condition and stage of the disease. Most often, aplastic anemia is complicated by infectious diseases. Even a common cold can lead to bronchitis, pneumonia, sinusitis, pharyngitis, etc. Also, with aplastic anemia, stomatitis and various skin diseases, infections of the genitourinary system are often found.

Also a complication of the disease is hemorrhagic syndrome. It manifests itself in increased bleeding of the mucous membranes. When blowing the nose, the patient often bleeds from the nose, each brushing of the teeth leads to bleeding and soreness of the gums. Hematomas, bruises with bruises or even without them may appear on the patient’s body. With cuts and scratches, the blood goes long and plentifully.

This complication is observed with a sharp and significant decrease in the level of red blood cells in the blood. Aplastic anemia leads to disruption of all organs and systems of the body. There are violations of the digestive tract, kidneys, heart, tachycardia is often found, liver cells suffer.

Unfortunately, the prognosis for this disease is often disappointing. The younger the patient and the less pronounced the disease, the greater the chance of recovery. If there is a large amount of adipose tissue in the bone marrow, we can talk about the irreversibility of the consequences of the disease. The disease can be fatal within 2 months or a year with constant treatment. In case of successful bone marrow transplantation, five-year survival is observed in 80% of patients.

The acquired form of aplastic and hypoplastic anemia is considered a multifactorial (polyetiological) disease caused by many causes (exogenous and endogenous factors).
) This means that it could arise due to any circumstances that turned out to be unfavorable for the bone marrow.

  • Any infectious agent, starting with childhood infections and ending with those that constantly live in a person or surround him even from time to time. The causative agents of measles and rubella, chickenpox, tuberculosis, scarlet fever, mumps, commonly called “mumps”, staphylococcal infection, Epstein-Barr virus, hepatitis, influenza, herpes, which carries about 90% of the world’s population, cytomegalovirus, parvovirus B 19 – all these infections are potential triggers of the start of the pathological process in the bone marrow;
  • Vaccination, exposure to allergens and toxins accidentally ingested;
  • Medications periodically or constantly taken by the patient for the treatment of chronic diseases (gold preparations, many antibiotics, non-narcotic painkillers, including acetylsalicylic acid derivatives, anti-TB drugs, psychotropic and sedative drugs, antitumor drugs – cytostatics, and many others);
  • Chemicals used in production, agriculture and emitted by transport (light (gasoline) and aromatic (benzene) hydrocarbons, insect and pesticides, mercury and nitric acid vapors, lead, etc.);
  • Ionizing radiation, which disrupts the proliferation and maturation of cells in CM, and the incidence rate correlates with the dose received;
  • In other cases – constant work with vibrating devices, in the high-frequency zone and with artificial lighting;
  • Severe physical trauma (especially head injury);
  • Psycho-traumatic situations (persistent, characterized as chronic stress).
  • Dysfunction of individual endocrine glands (“thyroid gland”, ovaries, thymus);
  • Immunopathological processes affecting the connective tissue (systemic lupus erythematosus – SLE, Sjogren’s syndrome, rheumatoid arthritis);
  • Sometimes – pregnancy (though, after childbirth, usually the symptoms of the disease disappear).

In addition, there is already information about the formation of bone marrow aplasia with fungal lesions and helminthic invasions.

The treatment of different types of anemia, in principle, is not very different. However, since there is a suspicion of drugs and toxic agents, the first step in therapy will be the exclusion of all contact with these factors. Otherwise, after the debut of aplasia, a second attack will follow and then, due to the development of anaphylactic shock, it is most likely impossible to save the patient.

17. violation
physiological functions and
compensatory adaptive reactions
with anemia

18.
hemolytic disease of the newborn

19.
iron deficiency and aplastic anemia
in children

20.
leukocyte formula and its violations
in conditions of pathology.

See trace
questions if you want to describe in more detail

21. Leukocytosis, Their
types, reasons. Leukocyte reaction phases
with infectious processes.

1. True

Increase
white blood cell count, i.e. leukocytosis, may
be associated with increased hematopoiesis.
due to
a number of physiological reasons:
leukocytosis
newborns
reaching
10-20 g / l
during
pregnancy and
in premenstrual
period.
Relative
leukocytosis is associated with an increase
certain forms of white blood cells

physical
work, digestion, emotional
stress. Distinctive features
distribution leukocytosis is
lack of changes in leukocyte
formula and functional activity
cells. (it happens physiological and
pathological)

3.
Pathological
leukocytosis
more often
found in inflammatory
processes and fever accompanying
infectious diseases being
body defenses against
infect, intoxication,

blood loss
tumors. The introduction of foreign proteins
also lead to the development of leukocytosis.

4. LEukocytosis
NEUTROPHILIC TYPE
or
NEUTRO

PHILIA
.
Exist
several types of neutrophilic
leukocytosis
depending on
as far as
severe bone marrow irritation
tissue as far as
strong regeneration.
These types
neutrophilic leukocytosis differ
the ratio of individual forms of white blood cells
between themselves and the character

are terized
varying degrees of regenerative
core shift or,
according to Arnet
core shear
to the left.

A) NEUTROPHIL
Leukocytosis without shift
.

This
a type of neutrophilia,
leaking
with an increase in the absolute amount
segmented white blood cells and saved
the ratio of neutrophilic forms,
is observed
with some easily leaking
infections with
jade and
also on the first day of myocardial infarction,
physiological
leukocytosis,
upon introduction
norepinephrine.

B)
NEUTROPHIL
HYPORGENERATIVE LEukocytosis

SHIFT
characterized by
predominant increase in content
stab forms over 6
% Is observed
with easily current infectious
diseases
sore throat,
after some
operations when
appendicitis, etc.

C) NEUTROPHIL
Leukocytosis with regenerative shift

GOM
characterized by
as well as
increase in the number of stab
forms, increase
young or metamyelocytes.
This type
neutrophilia is recorded
with croupous
pneumonia
typhus,
abscesses
malaria and others

Forms of the disease

Aplastic anemia is a disease in which the bone marrow stops producing enough blood cells.

Aplastic idiopathic anemia is characterized by a number of symptoms that can be divided into several groups. Symptoms of the disease are usually associated with impaired blood functions and are quite typical for many types of anemia.

Idiopathic aplastic anemia is accompanied by a violation of the production of all blood cells: platelets, white blood cells, red blood cells, lymphocytes.

Symptoms of aplastic anemia:

  • Anemia This is a syndrome of decreased production of red blood cells in the blood. The patient complains of poor health, dizziness, general weakness, fatigue, poor mood, lack of appetite. He has pale skin, tachycardia, insomnia, shortness of breath. Also, tinnitus and a decrease in libido often appear. The patient may complain of impaired attention and memory. These are typical signs of anemia that occur in any form.
  • Leukopenia With a decrease in the level of leukocytes, the body begins to attack various infections. Immunity is significantly reduced, the patient often begins to get sick for a long time. Often, recovery occurs only after taking antibiotics, but then relapse begins. Infection can affect the upper respiratory tract, oral cavity, heart, and other organs. Infectious diseases against the background of leukopenia are difficult and often with complications.
  • Thrombocytopenia. With a decrease in platelet count, the blood coagulation process is disrupted. Hemorrhages, bruises and bruises can appear on the patient’s skin with the slightest bruise, frequent bleeding from the gums when brushing your teeth, nosebleeds, women have heavy and prolonged periods, and blood in the urine can also appear. With symptomatic treatment, these symptoms are paid attention first of all, since bleeding can be fatal.
  • Lymphopenia The number of lymphocytes is also significantly reduced. Lymph performs many different functions, so reducing its amount can lead to the development of infectious, oncological or autoimmune diseases. As a rule, lymphopenia is asymptomatic, and manifests itself already at the stage of complications. The patient develops or returns chronic infections, as well as various skin diseases (eczema, dermatitis).

Complete blood count – an effective diagnosis of idiopathic aplastic anemia

The term “idiopathic” implies that the true causes of aplastic anemia are unknown. The causes of this disease are still reliably unknown, often they are associated with hormonal and autoimmune malfunctions in the body, internal processes.

However, there may be external causes of aplastic anemia:

  • Intoxication. Various toxic substances with constant contact with them can be the cause of aplastic anemia. If this cause is established, then treatment begins with the termination of contacts and elimination of the effects of intoxication.
  • Radiation. Ionizing radiation disrupts the production of blood cells. The degree of development of the disease directly depends on the level of radiation and its duration. In some cases, with prolonged exposure, the effects may be irreversible.
  • Medicinal substances. Some drugs can negatively affect bone marrow. With prolonged use, severe anemia develops. Such drugs include some antibiotics, indomethacin, phenothiazine.
  • Infections Among infections, severe hepatitis can lead to aplastic anemia. Most often, among the infectious causes of this disease, hepatitis A and B are noted.
  • Alcoholism. A direct link between alcohol abuse and the development of aplastic anemia has not been established, but alcohol has a negative effect on all body systems and the immune system, including, which can serve as a prerequisite for the development of the disease.

Diagnosis of aplastic anemia in the initial stages is simple. A general blood test is enough to detect a decrease in the blood of red blood cells, platelets and white blood cells (especially neutrophils). These indicators can decrease all at the same time or in turn, gradually. ESR (erythrocyte sedimentation rate) is increased.

This is not the most pleasant procedure in which bone marrow tissue is taken for examination using a thin needle to pierce the sternum. Microscopic examination in the case of aplastic anemia in the tissues of the bone marrow will reveal a large number of fat cells.

Hereditary and acquired forms of the disease are distinguished.

  • hereditary hypoplastic anemia with the defeat of three hematopoietic sprouts – with and without congenital malformations (Fanconi anemia) (Estren-Dameshek anemia);
  • hereditary partial anemia with selective lesion of erythropoiesis (anemia of Joseph – Blackfen – Diamond);
  • congenital dyskeratosis.
  • acquired anemia with the defeat of all three hematopoietic sprouts – acute, subacute, chronic;
  • acquired partial anemia with selective lesion of erythropoiesis – idiopathic (Erlich form) and known etiology.

According to the severity of the process, aplastic anemia is:

  • mild (granulocytes – 2,0 x 10 9 / l, platelets – less than 50 x 10 9 / l, a moderate decrease in bone marrow cellularity);
  • severe (granulocytes – less than 0,5 x 10 9 / l, platelets – less than 20 x 10 9 / l, reticulocytes – less than 1%, partial aplasia of red bone marrow);
  • very severe (granulocytes – less than 0,2 x 10 9 / l, platelets – less than 20 x 10 9 / l, complete fatty degeneration of the red bone marrow).

Aplastic anemia also develops with and without hemolytic syndrome.

Symptoms

the disease begins suddenly, progresses rapidly and practically does not respond to treatment. But still, more often she comes little by little, gradually changing the picture of blood. The patient does not notice anything for a long time, since the process is smooth, adapts to lower blood cells. But for the time being, because once a critical moment arrives, forcing to seek help.

Acute anemia is a commonly acquired variant of the disease. It should be noted that the acute superheavy form is rapidly progressing, it is difficult to fight it, for several weeks, without looking at the intensive measures taken, the patient dies.
Super severe anemia often (10 times more often than the rest) develops in people who have been treated with chloramphenicol, known under the name – chloramphenicol.

With congenital and hereditary forms, the disease has a predominantly chronic course.
Chronic anemia lasts for a long time – sometimes calming down, then exacerbating, leaving the patient a chance of life, because nevertheless sometimes leads to a complete deliverance from the disease, that is, recovery.

All symptoms of aplastic anemia are combined into 3 main groups of syndromes: anemic syndrome, hemorrhagic syndrome, infectious complications syndrome.

Anemic syndrome is characterized by:

  • severe general weakness;
  • fatigue;
  • intolerance of habitual physical activity;
  • shortness of breath and tachycardia with moderate exertion, in severe cases – at rest, with a change in body position;
  • headaches, dizziness, episodes of fainting;
  • noise, ringing in the ears;
  • feeling of a “stale head”;
  • flickering of “flies”, spots, colored stripes in front of the eyes;
  • stitching pains in the region of the heart;
  • decreased concentration;
  • violation of the “sleep – wakefulness” regime (drowsiness during the day, insomnia at night).

Objectively, when examining patients, pallor of the skin and visible mucous membranes, muffled heart sounds, increased heart rate, and decreased blood pressure are established.

Hemorrhagic syndrome manifests itself:

  • hematomas (bruises) of different sizes and pinpoint hemorrhages that occur on the skin and mucous membranes after a minor exposure or spontaneously, for no reason;
  • bleeding gums;
  • bleeding from the nose;
  • in women – uterine intermenstrual bleeding, prolonged heavy menstruation;
  • pink staining of urine;
  • determination of blood traces in stool;
  • possible massive gastrointestinal bleeding;
  • hemorrhages in the sclera and fundus;
  • hemorrhages in the brain and its membrane;
  • pulmonary bleeding.

Objective confirmation of hemorrhagic syndrome – point hemorrhages and bruises on the skin and mucous membranes, multiple hematomas at different stages (from purple-violet to yellow).

Infectious complications are represented by developing pneumonia, pyelonephritis, furunculosis, post-injection abscesses or infiltrates, in severe cases – sepsis.

Signs of the disease appear as a result of a decrease in the number of certain blood cells.

• weakness. • Shortness of breath on exertion. • Fast or irregular heartbeat. • Pallor of the skin. • Frequent and severe infections. • Tendency to bruises. • Bleeding from the gums and nose. • Prolonged bleeding after cuts. • Skin rash. • Dizziness. • Headache.

Aplastic anemia can progress slowly, weeks and months. The disease can be short and passing, and can become chronic. Aplastic anemia requires a serious attitude, because in severe cases it ends fatally.

Clinical signs of aplastic anemia develop acutely or may occur gradually. It depends on the cause of the disease and the intensity of exposure to the body of damaging factors. With hereditary forms, a slow development of pathology is characteristic, in the case of toxic effects of chemicals, radiation, medications, symptoms grow rapidly.

At the beginning of the disease, a hypoplastic form of anemia occurs, in which the blood-forming sprouts are partially suppressed. The bone marrow retains the ability to form cells, but in a much smaller volume. The aplastic process implies complete inhibition of hematopoiesis, which leads to a critical decrease in the concentration of red blood cells, platelets, white blood cells.

The clinical picture consists of 3 syndromes: anemic, hemorrhagic, infectious. A syndrome is a collection of symptoms that are characteristic of a disease. Anemic and hemorrhagic manifestations occur first, then infectious complications join. The severity of the clinical signs depends on the cause of the disease.

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Anemic syndrome

It occurs due to inhibition of the red germ of hematopoiesis. The content of red blood cells, which carry oxygen to organs and tissues, is reduced. In this case, the concentration of hemoglobin in the cells corresponds to the norm, since the body has enough substances for its synthesis. Due to the low content of red blood cells, hypoxia (oxygen starvation of tissues) develops. The normal functioning of the organs is disturbed. Chronic heart, kidney, and liver failure develops. Brain function suffers.

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Anemic syndrome is manifested by rapid fatigue, weakness, drowsiness. There is dizziness, frequent headaches, decreased visual and hearing acuity, flickering of “flies” in front of the eyes. Disruptions in the work of the heart are characteristic, which are accompanied by tachycardia, instability of blood pressure, arrhythmias, the appearance of noise when listening to (auscultation) of the heart.

The skin becomes dry and pale. Due to frequent blood transfusions (blood transfusions), it becomes icteric, which is associated with hemolysis (destruction) of red blood cells. Metabolic deterioration due to hypoxia leads to stratification of nails, hair loss, destruction of tooth enamel. Long non-healing ulcers are formed on the legs.

Appears due to impaired formation of platelet precursors in the red sprout of hematopoiesis. These cells are responsible for the formation of vascular clots to stop and prevent bleeding. More often hemorrhagic syndrome occurs immediately with anemic or somewhat later. In a rare disease – amegakaryocytic aplasia, inhibition of platelet formation comes to the fore, which can lead to an erroneous diagnosis.

The syndrome is characterized by bleeding of varying severity. Small and large hemorrhages appear in the skin – a hemorrhagic rash. The tendency to bruises and hematomas leads to the attachment of a secondary infection and suppuration. Frequent bleeding from the nose and gums, heavy menstruation are characteristic, and the time for stopping bleeding increases. The skin becomes spotty due to numerous bruises.

The progression of the disease leads to massive bleeding from the lungs, stomach and intestines. Cerebral hemorrhage causes a hemorrhagic stroke and is associated with a high risk of death.

Inhibition of the white sprout of hematopoiesis leads to a disruption in the formation of white blood cells. The number of segmented cells decreases (when viewed under a microscope, inclusions are noticeable in the nucleus). These include neutrophils (see “Neutropenia”), basophils (see “Basopenia”) and eosinophils (see “Eosinopenia”). Other cells of the leukocyte formula (monocytes, lymphocytes) are usually at the level of normal indicators, and when viewed with respect to segmented white blood cells, their concentration in the blood rises.

Since the white sprout of hematopoiesis forms the body’s immune defense, as a result, the ability to resist bacterial and viral infections, helminth infections, and the formation of tumors is impaired. A characteristic severe respiratory illness, inflammation of the genitourinary tract, and lungs. Often infections of the skin occur, scratches and wounds do not heal for a long time. Skin lesions are prone to suppuration. A high risk of sepsis (blood poisoning) worsens the course of the disease.

Aplastic anemia – the cause, diagnosis and treatment of anemia

Table – Laboratory diagnosis of aplastic anemia

Complete blood count (KLA)

HemoglobinLow level (below 110 g / l)Red blood cells (red blood cells)Below the norm (less than 2,5×10 * 12 / l) – erythropeniaHematocrit (ratio of the liquid part of the blood and the formed elements)Decrease level (below 30)ReticulocytesDecrease in an indicator (0,2% and less)PlateletsLow content (less than 100×10 * 9 / l) – thrombocytopenialeukocytesSignificantly lower than normal (0,2-2,5×10 * 9 / l) – leukopeniaMature neutrophils (segmented)

Young neutrophils (stab)

Less than 40% (at a rate of 50-72%)

Below 2% (typical 6%)

BasophilsNone (normal 0-1%)EosinophilsNot in the blood or 1% (usual indicator 1-5%)MonocytesHigh rate (over 8%) due to relative increase – monocytosisMyelocytes (progenitor cells)Appearance in the blood (normally absent)LymphocytesHigh rate (above 40%) due to relative increase – lymphocytosisColor indicator (CPU) – the degree of saturation of red blood cells with hemoglobinOK (0,85-1,05)Red blood cell sizeAnisocytosis (different sizes)The shape of red blood cellsPoikilocytosis (unusual form)ESR (erythrocyte sedimentation rate)Above the norm (more than 20 mm / h) with the development of infectionErythropoietin (a hormone that is synthesized by the kidneys and activates hematopoiesis)High rate due to compensatory increase with a lack of red blood cellsThymol test (evaluates the degree of inflammation against a background of low immunity function)Increase in the indicator (norm 0-4)Whey ironNormal indicator

An increase in the level of trace elements due to frequent blood transfusions

CRP (C-reactive protein)High level (more than 20 mg / l)ImmunologyHIV antibodiesDetect when infected with human immunodeficiency virusHBs-AH and anti-HBc IgG (antibodies against hepatitis B virus)A positive indicator for infectionAntibodies to CMV (cytomegalovirus) *Отрицательные

Positive after infection

Determination of blood type and Rh factorIt is necessary for the selection of donor bloodSternum puncture (cytological examination – myelogram)Red blood cell and white blood cell precursorsNoneYoung plateletsNot detected or singleTrepanobiopsy (myelogram and histological examination)Red blood cell, white blood cell, platelet precursorsMissing or critically smallStromaVolume increase compared to cell concentrationYellow bone marrow (inactive part of hematopoiesis)It grows and prevails over the red (active) bone marrow

* Antibodies to cytomegalovirus are determined before blood transfusion. If a person is not infected with the virus, he will receive CMV-negative blood.

Sternal puncture and trepanobiopsy are mandatory examination methods for aplastic anemia. Only blood tests cannot make an accurate diagnosis. Sternal puncture is performed by puncture of the sternum at the level of 2-4 ribs with a hollow needle to collect a small amount of bone marrow. 10-15 smears on slides are prepared from the material obtained for microscopic examination (examination under a microscope). As a result, a deficiency of cells in the bone marrow is detected.

Trepanobiopsy is performed by piercing the ilium (one of the pelvic bones). The technique allows you to take a larger volume of bone marrow, to conduct not only cytological (study of cells), but also histological examination (assessment of tissue features). In addition, this method is more reliable for diagnosis at the first stages of the development of the disease, when there are islands of normal hematopoiesis.

Additionally, instrumental examination methods are prescribed:

  1. Ultrasound (ultrasound) of the internal organs – reveals a violation of the function and congenital malformations.
  2. ECG (electrocardiogram) – a study of the heart, rhythm and conduction disorders.
  3. CT / MRI (computed and magnetic resonance imaging) – identifies disorders in the structure of organs and neoplasms.
  4. X-ray of the hands – allows you to confirm congenital maldevelopment of bones.
  5. Genetic studies – assess the risk of Fanconi and Diamond-Blackfen anemia.

Diagnosis is carried out on an outpatient basis. In a serious condition of the patient and the appointment of a bone marrow puncture, they are referred to hospitalization in hematology.

Table – Differential Diagnostics

DiseaseDistinctive symptomsResults of the survey
Acquired aplastic anemiaAnemic syndrome

Frequent and severe infections

Liver and spleen not enlarged

Decreased red blood cells, white blood cells, platelets (pancytopenia)

Reduction of bone marrow progenitor cells

Fanconi AnemiaMalformations of the skeleton and internal organs

Pigmentation (darkening) of the skin

Children’s age (5-12 years)

Same as with the hereditary form

Fetal hemoglobin in the blood (characteristic of intrauterine development)

Acute Leukemia (Blood Cancer)Enlarged liver and spleenMore often, inhibition of one germ of hematopoiesis (rarely pancytopenia)

When conducting sternal puncture – tumor cells

B12 deficiency anemiaNo hemorrhagic and infectious syndrome

Digestive tract and nervous system damage

Macrocytosis in the blood (large sizes of red blood cells)

In the results of sternal puncture – megaloblasts

Myelodysplastic syndromeSymptoms of aplastic anemiaThere is no cell deficiency in the bone marrow

Genetic studies reveal characteristic chromosome changes

An important clinical sign of the disease is the absence of enlargement of the liver, spleen and lymph nodes.

  • Aplastic anemia causes weakness and fatigue in patients, and also makes them very susceptible to infections and bleeding.
  • Factors that temporarily or irreversibly disrupt the hematopoietic function of the bone marrow include:
  • Aplastic anemia should not be confused with myelodysplastic syndrome.

Aplastic anemia, a rare and serious condition, can occur at any age. Aplastic anemia can develop suddenly, but can progress slowly, worsening the patient’s condition for months. Current treatments for aplastic anemia include blood transfusions, medications, and bone marrow transplantation.

Aplastic anemia occurs with damage to the bone marrow, which leads to a slowdown or complete cessation of the production of blood cells. The bone marrow is a red spongy substance inside the bones, which constantly produces new blood cells – red blood cells, white blood cells, platelets. In aplastic anemia, a diseased bone marrow is described by the terms “aplastic” or “hypoplastic”, which means either a complete absence of young blood cells in it or a very small number of them.

• Radiation exposure. A person can become a victim of radiation both as a result of accidents at nuclear facilities, and as a result of medical exposure – for example, in the treatment of cancer. • Chemotherapy for cancer. The impact of many chemotherapeutic drugs has a bad effect not only on cancer cells, but also on other intensively dividing cells of the body.

• Toxic substances. Exposure to environmental toxins, such as insecticides, pesticides, laboratory reagents, can adversely affect bone marrow. In this case, the patient sometimes feels better if the exposure to chemicals ceases. • Some medications. Drugs for the treatment of rheumatoid arthritis, some antibiotics can cause aplastic anemia.

This side effect must be indicated in the instructions for the drug. • Autoimmune diseases. This is a large group of diseases in which the body’s immune system mistakenly attacks the host cells. Bone marrow cells can also become immunity victims. • Viral infection. Some viruses play a role in the development of aplastic anemia.

Recent studies allow us to rank Epstein-Barr virus, cytomegalovirus (CMV), parvovirus B19 and human immunodeficiency virus (HIV) as such dangerous organisms. • Pregnancy. Aplastic anemia that occurs during pregnancy may be associated with an autoimmune problem – the pregnant woman’s immune system sometimes mistakenly attacks the bone marrow.

• Unknown factors. In many cases, doctors cannot determine the exact cause of aplastic anemia. Then they talk about the so-called idiopathic aplastic anemia. This is a group of diseases in which the bone marrow produces new blood cells, but they are deformed or underdeveloped. In myelodysplastic syndrome, the bone marrow is sometimes characterized as “hyperplastic” – this means that it contains a lot of blood cells.

But in some patients with this syndrome, the bone marrow is almost empty, so the disease is sometimes confused with aplastic anemia. Aplastic anemia is associated with some other diseases. Some patients with aplastic anemia have another rare disease – paroxysmal nocturnal hemoglobinuria. This disease is characterized by too rapid destruction of red blood cells.

Fanconi anemia is a rare, hereditary disease that leads to aplastic anemia. Children with Fanconi’s disease can have various birth defects, such as underdevelopment of the limbs. The disease is diagnosed by genetic analysis.

Aplastic anemia is rare.

• Radiation or chemotherapy for cancer in the past. • Exposure to toxic substances at work and at home. • The use of prescription drugs such as chloramphenicol (chloramphenicol) and some anti-rheumatoid arthritis drugs. • Some diseases of the hematopoietic system. • Severe infectious diseases.

• weakness. • Shortness of breath on exertion. • Fast or irregular heartbeat. • Pallor of the skin. • Frequent and severe infections. • Tendency to bruises. • Bleeding from the gums and nose. • Prolonged bleeding after cuts. • Skin rash. • Dizziness. • Headache. Aplastic anemia can progress slowly, weeks and months.

The disease can be short and passing, and can become chronic. Aplastic anemia requires a serious attitude, because in severe cases it ends fatally. To diagnose this disease, your doctor may prescribe the following: • Blood tests. In the blood of a healthy person, the level of red blood cells, white blood cells and platelets is within certain limits.

These limits may vary depending on age, gender, race and other characteristics of the body. But if the analyzes show a very low level of all three classes of blood cells, then the doctor will suspect aplastic anemia. • A bone marrow biopsy. To confirm the diagnosis, the patient will have to undergo a painful, but necessary biopsy procedure.

During the biopsy, the doctor will insert a special needle into one of the bones and take a bone marrow sample. Bone marrow cells will be examined under a microscope to see signs of aplastic anemia or other diseases. With aplastic anemia, the bone marrow will be low in blood cells. After aplastic anemia is confirmed, doctors will prescribe additional examinations to find out the cause of the disease.

This can be a lengthy and complex process. Treatment of aplastic anemia in mild cases may consist of simply observing the patient. With a more severe form of the disease, blood transfusions, bone marrow transplantation, and special medications that stimulate blood formation can be used. Severe aplastic anemia threatens a person’s life and requires mandatory hospitalization.

With a low level of platelets or red blood cells, patients receive transfused donor blood. This will not cure aplastic anemia, but will help control its symptoms by replenishing blood cells that a diseased bone marrow does not produce. For transfusion, a separate mass can be used, consisting of red blood cells or platelets – depending on the needs of the patient.

There is usually no limit to the number of transfusions per patient. But such a procedure can have complications. Transfused blood cells contain iron, which is released during their destruction and accumulates in the body. With multiple transfusions, large reserves of iron are deposited in the body, which damage vital organs, unless special drugs are prescribed for its excretion.

Another complication is that the body can produce antibodies to transfused cells. And this will make the treatment less effective. A stem cell transplant to restart a patient’s bone marrow is sometimes the only way to successfully treat aplastic anemia. Stem cell transplantation, sometimes called bone marrow transplantation, is the treatment of choice for young patients with a suitable donor.

Most often, a suitable donor is a brother or sister. If a donor is found, then the patient’s bone marrow is first depleted with high doses of radiation or chemotherapy. Next, the healthy stem cells of the donor are filtered from his blood, after which they are introduced into the bloodstream of the patient. Cells themselves migrate into the bone cavity and begin to produce blood cells there, as provided by nature.

But the whole procedure is very complicated, expensive and requires a long stay in the hospital. After transplantation, the patient should receive medications to prevent donor cell rejection. Transplantation entails risks. There is a chance that the body will begin to reject the transplant. This reaction can be fatal to the recipient.

In addition, not every patient manages to find a donor that is compatible in all respects. Patients with autoimmune diseases that have damaged the bone marrow need treatment with immunosuppressants – drugs that suppress immunity. The drug cyclosporin (Gengraf, Neoral) and antithymocyte globulin (Timoglobulin) can be used as an example.

These drugs suppress the activity of immune cells that attack bone marrow. Treatment helps restore bone marrow and increase blood cell levels. The two drugs mentioned above are often used in combination. Corticosteroid hormones, such as methylprednisolone (Solu-Medrol, Medrol, Metipred), are also prescribed to suppress immunity, sometimes along with other medicines.

Immunosuppressants can be very effective in aplastic anemia. The flip side of the coin is that suppressing immunity leads to a risk of infections. In addition, there is the possibility that after drug withdrawal, aplastic anemia will return. Some drugs help enhance blood formation in the bone marrow.

Among them, colony-stimulating factors, such as sargramostin (Leukin), filgrastim (Neupogen), pegfilgrastim (Neulast) and epoetin-alpha (Procrit, Epogen). These drugs have been developed relatively recently, their preparation is a very expensive and time-consuming process, so the cost of drugs for the average patient is simply fantastic.

Colony-stimulating factors are often prescribed along with immunosuppressants. Aplastic anemia is accompanied by a decrease in the level of leukocytes and a weakening of the body’s immune defense. This makes the patient’s body very susceptible to various bacterial, viral and fungal infections. At the first sign of infection, such as fever, you should immediately consult a doctor.

A person with a weakened immune system has little chance that a common cold will go away “just like that.” A harmless infection for other people can become life-threatening, so the doctor will use antibiotics, antiviral and other drugs for treatment and prevention. Aplastic anemia caused by radiation or chemotherapy for cancer usually improves after treatment is withdrawn.

The same goes for many drugs and toxins that affect the bone marrow. Pregnant women with aplastic anemia receive blood transfusions because other treatments will cause irreparable harm to the baby. In many pregnant women, aplastic anemia goes away on its own shortly after childbirth. If this does not happen, further treatment is required.

  • general blood test (normochromic anemia with CP of 0,9 is detected, a decrease in the number of reticulocytes, granulocytes, a relatively small increase in the number of lymphocytes, a significant decrease in the number of platelets, an increase in ESR to 30–90 mm / h);
  • examination of red bone marrow (myelokaryocytes – less than 50 x 10 9 / l with a norm of 50 to 250 x 10 9 / l, megakaryocytes – 0 with a norm of 50 to 150 in 1 μl, leuko-erythroblastic ratio – 5: 1-6: 1 at a rate of 3: 1 or 4: 1);
  • trepanobiopsy of the iliac crest (fatty degeneration of the red bone marrow is established);
  • analysis of blood serum iron (increase to 60 μmol / l with a norm of up to 28);
  • bone marrow scan with Th99 (a significant decrease in bone marrow activity in the spine, flat bones, and heads of tubular bones is detected).

Aplastic anemia – the cause, diagnosis and treatment of anemia

With a low platelet or red blood cell count in patients

. This will not cure aplastic anemia, but will help control its symptoms by replenishing blood cells that a diseased bone marrow does not produce. For transfusion, a separate mass can be used, consisting of red blood cells or platelets – depending on the needs of the patient.

There is usually no limit to the number of transfusions per patient. But such a procedure can have complications. Transfused blood cells contain iron, which is released during their destruction and accumulates in the body. With multiple transfusions, large reserves of iron are deposited in the body, which damage vital organs, unless special drugs are prescribed for its excretion.

Another complication is that the body can produce antibodies to transfused cells. And this will make the treatment less effective.

A stem cell transplant to restart a patient’s bone marrow is sometimes the only way to successfully treat aplastic anemia. Stem cell transplantation, sometimes called bone marrow transplantation, is the treatment of choice for young patients with a suitable donor. Most often, a suitable donor is a brother or sister.

If a donor is found, then the patient’s bone marrow is first depleted with high doses of radiation or chemotherapy. Next, the healthy stem cells of the donor are filtered from his blood, after which they are introduced into the bloodstream of the patient. Cells themselves migrate into the bone cavity and begin to produce blood cells there, as provided by nature.

Transplantation entails risks. There is a chance that the body will begin to reject the transplant. This reaction can be fatal to the recipient. In addition, not every patient manages to find a donor that is compatible in all respects.

Patients with autoimmune diseases that have damaged the bone marrow need treatment with immunosuppressants – drugs that suppress immunity.

The drug cyclosporin (Gengraf, Neoral) and antithymocyte globulin (Timoglobulin) can be used as an example. These drugs suppress the activity of immune cells that attack bone marrow. Treatment helps restore bone marrow and increase blood cell levels. The two drugs mentioned above are often used in combination.

Corticosteroid hormones, such as methylprednisolone (Solu-Medrol, Medrol, Metipred), are also prescribed to suppress immunity, sometimes along with other medicines.

Immunosuppressants can be very effective in aplastic anemia. The flip side of the coin is that suppressing immunity leads to a risk of infections. In addition, there is the possibility that after drug withdrawal, aplastic anemia will return.

Some drugs help enhance blood formation in the bone marrow. Among them, colony-stimulating factors, such as sargramostin (Leukin), filgrastim (Neupogen), pegfilgrastim (Neulast) and epoetin-alpha (Procrit, Epogen). These drugs have been developed relatively recently, their preparation is a very expensive and time-consuming process, so the cost of drugs for the average patient is simply fantastic. Colony-stimulating factors are often prescribed along with immunosuppressants.

Aplastic anemia is accompanied by a decrease in the level of leukocytes and a weakening of the body’s immune defense. This makes the patient’s body very susceptible to various bacterial, viral and fungal infections.

At the first sign of infection, such as fever, you should immediately consult a doctor. A person with a weakened immune system has little chance that a common cold will go away “just like that.” A harmless infection for other people can become life-threatening, so the doctor will use antibiotics, antiviral and other drugs for treatment and prevention.

Aplastic anemia caused by radiation or chemotherapy for cancer usually improves after treatment is withdrawn. The same goes for many drugs and toxins that affect the bone marrow.

Pregnant women with aplastic anemia receive blood transfusions because other treatments will cause irreparable harm to the baby. In many pregnant women, aplastic anemia goes away on its own shortly after childbirth. If this does not happen, further treatment is required.

• Relax when you need it. Anemia can cause fatigue and shortness of breath, even with a slight load. Take breaks in work, if you are tired, take care of your strength. • Avoid contact sports. Due to the high risk of bleeding associated with thrombocytopenia, contact sports can cause problems.

Supportive Supportive Therapy:

  • red blood cell transfusion;
  • transfusion of freshly frozen plasma;
  • the introduction of a concentrate of donor platelets;
  • desensitizing drugs;
  • antibiotic therapy in case of infectious complications.

With inefficiency, lymphocytapheresis, splenectomy, bone marrow transplantation are performed.

• Relax when you need it. Anemia can cause fatigue and shortness of breath, even with a slight load. Take breaks in work, if you are tired, take care of your strength. • Avoid contact sports. Due to the high risk of bleeding associated with thrombocytopenia, contact sports can cause problems.

A slight cut, a bruise, a drop – and the blood will be difficult to stop. • Protect yourself from germs. You can reduce the risk of infections if you wash your hands more often, avoid sick people, and follow good hygiene practices. At the first slight sign of infection, consult a doctor immediately. Regrettably, there are still no effective ways to prevent aplastic anemia. However, you can avoid insecticides, organic solvents and other toxins to reduce the risk.

Prevention of disease

Prevention of the development of anemia is aimed at eliminating adverse environmental factors (occupational and domestic hazards, radiation), unreasonable use of drugs toxic to bone marrow. This is the primary prevention of the disease. This also includes the prevention and timely treatment of infections.

Secondary prevention is carried out in case of an already existing disease. Patients need regular follow-up by a hematologist, regular examination and receiving supportive treatment.

Regrettably, there are still no effective ways to prevent aplastic anemia. However, you can avoid insecticides, organic solvents and other toxins to reduce the risk.

Konstantin Mokanov: Master of Pharmacy and professional medical translator

Anemia – Aplastic and Hypoplastic

Aplastic anemia most often forms at some stage of life and constitutes the first group of these pathological conditions (acquired AA), and the specific cause of the disease is rarely called (idiopathic aplastic anemia), in most cases it remains only assumed (see below). The second group of AA is congenital and hereditary pathology, which will also be described below.

The essence of the incomplete similarity is that these pathological conditions differ:

  • Origin (AA – the stem cell defect is stem cell, GA is the autoimmune component);
  • The degree of damage to hematopoiesis (AA – bone marrow aplasia, it can not produce anything, GA – hypoplasia, in which the inhibition of hematopoiesis is not so pronounced);
  • The mechanism of the development of the disease (pathogenesis);
  • The effectiveness of treatment measures (correctly selected therapy for hypoplastic anemia can provide long-term remission, which is very difficult to achieve with AA);
  • A prediction for a future life (in the case of AA, it is, of course, less encouraging).

Previously, these two conditions (aplastic and hypoplastic anemia) were considered different stages of the same process,
however, it is up to specialists to differentiate them, therefore, in the further description of the pathology, the reader will meet both terms.

AA treatment is difficult and, unfortunately, not always successful. The leading areas of therapeutic tactics are: bone marrow transplantation and the use of immunosuppressants
. But first things first…

Forecast

Although the prognosis of aplastic anemia was casually touched during the description of the disease, I would like to add a few more words.

The main cause of death in patients with AA is infection and bleeding. Some authors believe that very poor prognostic signs are: taking chloramphenicol (albeit in short courses) and the development of the disease after infectious hepatitis (severe bone marrow aplasia is considered as an indication for a KM transplant at the very beginning of the disease).

However, do not immediately despair and take AA as a death sentence.
The use of modern treatment methods, in general, improves the situation and allows many patients to significantly increase their life expectancy, and even get rid of a serious illness.

One of the leading ones will answer your question.

At the moment, answers the questions: A. Olesya Valeryevna, candidate of medical sciences, teacher of a medical university

Against the background of immunosuppressive therapy, the prognosis improved significantly: remission is achieved in approximately 50% of patients. Nevertheless, the survival rate of patients with severe aplastic anemia remains low: only 70-80% of patients survive a 5-year milestone. The prognosis for children is more favorable.

The duration and quality of life depends on the cause of anemia, the severity of the course, the occurrence of complications, the timing of bone marrow transplantation. After the operation, the prognosis is favorable in 40-98% of cases. Recovery is most likely after a transplant of your own stem cells.

An unfavorable prognosis often occurs with hereditary forms, acute course and rapid progression of the disease. A fatal outcome occurs due to massive bleeding and severe infections, which are difficult to antibiotic therapy.

Classification of Aplastic Anemia

The disease described at the end of the 19th century does not want to slow down, because the rapid movement of mankind to new knowledge and inventions pushes people to very close contact with factors that can lead to an abnormal state of the stem cell. As a result, the incidence rate is only growing, mortality from this pathology, although it is falling, thanks to the development of transplantology and treatment with the latest immunosuppressive drugs, but not to the extent that we would like.

Currently, two types of AA have been identified, containing several species, each of which has its own subspecies, based on the causes and clinical manifestations. It should be noted that the classification in different sources, although not significantly, is different, and the classification used to diagnose and treat adults is not entirely suitable for children and adolescents (for example, a form such as transient is often found in children AA – it will also be mentioned below).

    The true
    AA, which ≈ in 50% of cases is represented by idiopathic aplastic anemia (it is characterized by the suppression of all blood lines for no apparent reason), has three forms of flow:

  • about the stream
    , which lasts up to 2 months and ends with 100 percent death of patients;
  • subacute
    (hypo- and aplastic anemia with short-term stabilization in AA and alternating remissions and exacerbations in GA, the duration of the disease is 2 months or longer);
  • chronic
    hypo- and aplastic anemia, which has a relatively calm course, the suffering of the bone marrow and the patient’s body lasts from a year to 3 to 5 years, sometimes the process drags on to 10 years or more and in some cases leads to recovery.
  • Partial Red Cell Bone Marrow Aplasia
    (PACA) is an autoimmune anemia caused by the action of autoantibodies on antigens of KM erythrokaryocytes, as a result of which the production of red blood cells is strongly inhibited. The most common form is idiopathic, sometimes the development of PACA is due to the formation of a thymus tumor (thymoma). Some authors recall the existence of another type of anemia that occurs in older children – adolescent PACA
    having a favorable course;
  • Hypoplastic anemia with a hemolytic component
    – regarding this form, there are constant disagreements, as some authors argue that this pathology acts as a certain stage of paroxysmal nocturnal hemoglobinuria. Chronic hypoplastic anemia with a hemolytic component in relapses is accompanied by hemolytic crises
    that is its feature.
    1. Fanconi’s Constitutional Anemia
      (an autosomal recessive type of inheritance, manifested in homozygotes aged 4-10 years), is represented by two types: 1) anemia with gross anomalies in the development of organs, 2) anemia with small (minor) developmental defects;
    2. Joseph-Diamond-Blackfen Anemia
      (red cell aplasia of CM, the type of inheritance is not clarified, presumably autosomal dominant, but others claim that it is autosomal recessive), the disease manifests itself very early, by the age of 4 months, 2/3 of the children debut the first signs, in the remaining third they will appear by the year. Diamond-Blackfen anemia has two varieties: 1) anemia with anomalies in the development of organs, 2) anemia without anomalies;
    3. Familial hypoplastic anemia of Estren-Dameshek
      (familial hypoplastic anemia in children, which is characterized by a general lesion of blood formation in the absence of developmental defects).

    Since hypoplastic anemia in the case of congenital forms acts as one of the symptoms of the main pathology, in addition, the disease becomes visible from early childhood, it makes no sense to dwell on it in this work. Readers, most likely, are more concerned with the form that, in the course of life, can overtake any person, even if he was born completely healthy.

    In ICD-10, aplastic anemia is assigned code D61. The classification includes causes (etiology), the type of inhibited germ of hematopoiesis, the severity of the disease.

    By origin, anemia is:

    • congenital (constitutional) – arises due to genetic mutations;
    • acquired – develops when exposed to adverse environmental factors;
    • idiopathic (primary) – occurs for no apparent reason;
    • unspecified – if during the diagnosis the etiology could not be established.

    According to the inhibited germ of hematopoiesis, anemia is distinguished:

    • true – the formation of all bone marrow cells decreases (pancytopenia);
    • partial – inhibition of only one sprout of hematopoiesis, more often erythrocyte, occurs.

    The severity of anemia is:

    • heavy – neutrophils (type of white blood cells) 0,2-0,5×10 * 9 / l, reticulocytes (young red blood cells) less than 1%, platelets not more than 20×10 * 9 / l, with trepanobiopsy (bone marrow puncture for analysis) the number of cells is 50% of the norm;
    • moderate severity – neutrophils more than 0,5×10 * 9 / l, reticulocytes more than 1%, platelets no less than 20×10 * 9 / l, indicators of trepanobiopsy – 30%;
    • superheavy – neutrophils less than 0,2 × 10 * 9, bone marrow punctate analysis – less than 30%.

    Mild aplastic anemia does not exist. The disease always has a severe course and carries a risk of complications.

    Acquired AA

    For acquired AA, three flow patterns with distinct clinical and hematological features characteristic of each of them are also indicated:

    1. Superheavy form (as a rule, it is acute aplastic anemia, which develops rapidly and gives almost 100% mortality);
    2. Heavy;
    3. Light form, if you can call it that, rather, not heavy
      , which slightly changes the meaning, implying a satisfactory state of hematopoiesis and well-being of the patient.

    Acquired abnormalities of stem cells that give life to the entire community of shaped elements can arise for various reasons, the main of which will be useful to consider.

    Frequently Asked Questions

    Pancytopenia, detected by microscopic examination of the smear (general clinical blood test), gives reason to suspect aplastic anemia and suggests a set of measures to establish the diagnosis:

    • Repeated blood count with platelet count and;
    • Biochemical blood test (LHC);
    • Puncture of bone marrow for subsequent assessment of the state of all sprouts of blood formation;
    • Trepanobiopsy, which allows us to distinguish 2 options: the presence of small foci that carry out hematopoiesis or fatty degeneration of hematopoietic cells with the formation of inflammatory infiltrates.

    Perhaps the diagnostic measures will not end there and additional tests will be required to clarify the preliminary diagnosis:

    1. Cytogenetic analysis of CM and lymphocytes circulating on the periphery – to detect chromosomal aberrations, if any;
    2. Ultrasound examination (ultrasound) of the liver, spleen, thymus gland (in children, as in adults it has already completed its activity), lymph nodes;
    3. Determination of the presence of viruses in the body (Epstein-Barr, cytomegalovirus, markers of hepatitis, HIV, HSV, etc.);
    4. Computed tomography – CT scan (performed to exclude secondary CM hypoplasia)
    5. Immunological research (determination of the state of immunity at the cellular and humoral levels);
    6. Typing of class II HLA antigens (PCR) if a bone marrow transplant is suspected.

    Of course, before starting the examination, the doctor carefully collects and studies the family history, anamnesis of the patient’s life and illness. Diagnostic measures involving the use of instrumental methods (CT puncture), as well as performing operations after diagnosis (splenectomy, bone marrow transplantation) require the written consent of the patient or his parents (if such procedures are performed in children).

    Question: Is it possible to cure aplastic anemia?

    Answer: The only radical method of therapy is a bone marrow or stem cell transplant. The effectiveness of the operation is higher if the biological material is taken from the patient himself. In such cases, the probability of recovery is high. If donor bone marrow is transplanted, then the effectiveness of the operation is reduced due to the high risk of cell rejection and the need for prolonged use of toxic immunosuppressive drugs.

    Question: Is aplastic anemia a blood cancer or not?

    Answer: Oncological diseases arise due to the appearance of atypical cells in the body, which quickly grow and destroy normal tissues. Blood cancer causes the formation of such cells in the bone marrow. With aplastic anemia, hematopoiesis is impoverished. There are normal cells in the bone marrow, but in a critically small amount. Aplastic anemia is a serious illness, but it is not cancer.

    Question: Which diet is better to use?

    Answer: The diet includes an increased content of proteins and carbohydrates, limit the intake of fats. Recommended dietary meat (turkey, veal, chicken), fish (pelengas, carp, hake, pollock), seafood. Porridges, fruits and vegetables supply complex carbohydrates to the body, which are slowly absorbed and replenish the body’s energy reserves.

    Question: Can I treat the disease with folk remedies?

    Answer: Aplastic anemia refers to severe blood pathology, which is difficult to treat with drug therapy. Often, only a bone marrow transplant can help the patient. Folk remedies are ineffective in the fight against the disease.

    Question: When is Atgam used and what is its effectiveness?

    This is an immunosuppressive drug that eliminates the damaging effects of immunity on the bone marrow’s own cells. It is an anti-lymphocyte globulin made from horse blood.

    Intended for intravenous administration. It is prescribed simultaneously with other immunosuppressants – glucocorticoids and cyclosporine. Atgam is effective in the absence of indications for a bone marrow transplant, normalizes blood formation, improves general condition, and increases life expectancy.

    Svetlana Borszavich

    General practitioner, cardiologist, with active work in therapy, gastroenterology, cardiology, rheumatology, immunology with allergology.
    Fluent in general clinical methods for the diagnosis and treatment of heart disease, as well as electrocardiography, echocardiography, monitoring of cholera on an ECG and daily monitoring of blood pressure.
    The treatment complex developed by the author significantly helps with cerebrovascular injuries and metabolic disorders in the brain and vascular diseases: hypertension and complications caused by diabetes.
    The author is a member of the European Society of Therapists, a regular participant in scientific conferences and congresses in the field of cardiology and general medicine. She has repeatedly participated in a research program at a private university in Japan in the field of reconstructive medicine.

    Detonic