Leukopenia and agranulocytosis. Agranulocytosis: symptoms and treatment What is blood agranulocytosis

). This is a clinical and hematological syndrome of a number of diseases in which the body’s susceptibility to infections increases. In women, agranulocytosis develops several times more often than in men. Typically, pathology is found in people over 40 years of age.

Granulocytes got their name due to the presence of a special granularity in the cytoplasm, which is detected when stained with certain dyes. Since granulocytes predominate in the structure of the leukocyte formula, the disease is accompanied.

Neutrophils form the basis of granulocytes (more than 90%). These are blood cells that perform a protective function in the body, providing the process of phagocytosis and killing tumor cells. They absorb microbes, damaged cellular elements, foreign bodies and tissue debris, produce lysozyme to fight bacteria and interferon to inactivate viruses.

The main functions of the predominant neutrophil granulocytes are the following:

• Maintaining immunity at an optimal level,
• Activation of the blood coagulation system,
• Ensuring blood sterility.

Granulocytes are produced by bone marrow cells. This process occurs especially intensively during infectious inflammation. Cells (primarily neutrophils) quickly die at the site of inflammation and become part of the pus.

Due to the widespread use of modern cytostatic agents and radiation therapy, the incidence of pathology has increased significantly. In the absence of adequate and timely therapy, severe complications of agranulocytosis develop: sepsis, hepatitis, mediastinitis, peritonitis. Mortality in the often recorded acute form of agranulocytosis reaches 80%.

Causes

Agranulocytosis is a serious pathology that does not occur just like that. The causes of the disease are very significant and varied.

Endogenous causes:

• Genetic predisposition,
• Diseases of the immune system - collagenosis, thyroiditis, glomerulonephritis, ankylosing spondylitis, systemic lupus erythematosus,
• , aplastic anemia,
• Metastatic bone marrow lesions,
• Cachexia.

Exogenous factors:

1. Epstein-Barr virus, cytomegalovirus infection, viral hepatitis, tuberculosis,
2. Bacterial infection occurring in a generalized form, sepsis,
3. Taking certain medications - cytostatics, beta-lactam antibiotics, Aminazin,
4. Long-term radiotherapy
5. Exposure to the body of toxic chemicals - benzene, arsenic, mercury, insecticides,
6. Chemical substances included in cosmetics, household chemicals, paint and varnish products,
7. Poor quality alcohol.

Classification

Agranulocytosis, depending on its origin, can be congenital or acquired. Congenital pathology is genetically determined and is practically not registered.

According to the clinical course, agranulocytosis can be acute and recurrent or chronic.

Pathogenetic classification of acquired form of pathology:

• Myelotoxic agranulocytosis or cytostatic disease,
• Immune or hapten - with the formation of autoantibodies in the human body,
• Idiopathic or genuine - etiology and pathogenesis have not been established.

agranulocytosis in the blood (left) and impaired cell production in the bone marrow (right)

Immune agranulocytosis

Immune agranulocytosis develops as a result death of mature granulocytes under the influence of antibodies. Neutrophil precursor cells are detected in the blood, which indicates stimulation of the formation of these cells and confirms the diagnosis. The death of a huge number of granulocytes leads to poisoning of the body and the appearance of signs of intoxication syndrome, which are often accompanied by symptoms of the underlying disease.

• Autoimmune agranulocytosis is a symptom of systemic autoimmune diseases: collagenosis,. Antibodies are formed in the blood to the body's own tissues. The trigger mechanism is considered to be hereditary predisposition, viral infections and psychological trauma. The outcome and course of autoimmune agranulocytosis is determined by the characteristics of the underlying disease.
• Hapten agranulocytosis is a severe form of pathology that occurs in response to the administration of a certain medication. Haptens are chemical substances that acquire their antigenic properties after interaction with granulocyte proteins. Antibodies attach to the surface of leukocytes, stick together and destroy them. Medicines that often act as haptens: “Diacarb”, “Amidopyrine”, “Acetylsalicylic acid”, “Analgin”, “Indomethacin”, “Trimethoprim”, “Pipolfen”, “Isoniazid”, “Erythromycin”, “Butadione”, “ Norsulfazol", "Ftivazid", "PASK". A course of taking these medications leads to the development of hapten or drug agranulocytosis. It begins acutely and continues to develop even after extremely low doses of drugs.

Myelotoxic agranulocytosis

Myelotoxic agranulocytosis is a consequence of radiation or cytotoxic therapy, under the influence of which the growth of granulocyte precursor cells in the bone marrow is suppressed.

All granulocytes have common precursors - bone marrow cells (myeloblasts)

The severity of the disease depends on the dose of ionizing radiation and the toxicity of the antitumor drug. The production of myelopoiesis cells is also suppressed by taking cytostatics - Methotrexate, Cyclophosphamide, as well as some antibiotics from the group of penicillins, aminoglycosides, and macrolides.

1. With myelotoxic endogenous agranulocytosis, the formation of blood cells in the red bone marrow is suppressed by tumor toxins. Gradually, bone marrow cells are replaced by cancer cells.
2. The exogenous form of pathology is a symptom of a serious disease, the cause of which is the negative influence of external factors. Bone marrow cells multiply intensively and are highly sensitive to any negative environmental influences.
3. The medicinal type of pathology occurs under the influence of cytostatics, which are widely used in the treatment of cancer and systemic diseases. Cytostatics suppress the activity of the immune system and the formation of granulocytes.

Symptoms

Myelotoxic agranulocytosis is often asymptomatic or manifests itself with symptoms of hemorrhagic syndrome and necrotizing enteropathy:

• Uterine and nosebleeds,
• The appearance of hematomas and hemorrhages on the skin,
• Blood in the urine
• Cramping pain in the abdomen,
• Vomiting
• Diarrhea,
• Rumbling and splashing in the stomach, flatulence,
• Blood in the stool.

Inflammation of the intestinal mucosa leads to the development of necrotizing ulcerative enteropathy. Ulcers and foci of necrosis quickly form on the lining of the digestive tract. In severe cases, life-threatening profuse intestinal bleeding develops or an acute abdomen appears.

Similar processes can occur on the mucous membrane of the genitourinary organs, lungs, and liver. Inflammation of the lungs with agranulocytosis has an atypical course. Large abscesses form in the lung tissue and gangrene develops. Patients experience cough, shortness of breath, and chest pain.

Distinctive signs of immune agranulocytosis are:

1. Acute onset
2. Fever,
3. Pale skin
4. Hyperhidrosis,
5. joint pain,
6. Gingivitis, stomatitis, pharyngitis, tonsillitis,
7. Putrid odor from the mouth,
8. Hypersalivation,
9. Dysphagia,
10. Regional lymphadenitis,
11. Hepatosplenomegaly.

Ulcerative-necrotic changes in the oral mucosa are caused by its high population and uncontrolled proliferation of saprophytic microflora. Inflammation of the pharynx, tonsils and gums quickly becomes necrotic. Bacteria accumulate and multiply under the films. Their toxins and breakdown products quickly penetrate into the general bloodstream, which is manifested by severe intoxication, fever, chills, nausea and headache. The diagnosis of immune agranulocytosis is confirmed by the detection of anti-leukocyte antibodies during a serological study.

In children from hereditary forms, Kostman's agranulocytosis most often develops. Both mother and father can be carriers of the altered gene. In patients, the composition of the blood changes and mental development is impaired. Despite the complete absence of neutrophils, the number of lymphocytes remains normal. Such children lag behind their peers in physical and mental development. The cause of the gene mutation has not yet been established. In newborns, purulent rashes often appear on the skin, ulcers and hemorrhages on the oral mucosa. Older children develop otitis, rhinitis, and pneumonia. These pathologies are accompanied by fever, lymphadenitis, and hepatosplenomegaly.

The disease in children is chronic. Exacerbations are accompanied by the appearance of ulcers on the mucous membrane of the mouth and pharynx. With an increase in granulocytes in the blood, remission occurs. As the child gets older, the symptoms gradually soften.

Complications of severe forms of agranulocytosis are: intestinal perforation, peritonitis, pneumonia, abscess formation of lung tissue, septic blood damage, respiratory failure, damage to the genitourinary system, endotoxic shock.

Diagnostics

Diagnosis of agronulocytosis is mainly laboratory. Specialists pay attention to the main complaints of patients: fever, hemorrhages and ulcerative-necrotic lesions on the mucous membrane.

Diagnostic measures to detect agranulocytosis:

• General clinical blood test – leukopenia, .
• General clinical urine analysis - proteinuria, cylindruria.
• Sternal puncture, myelogram, immunogram.
• Blood test for sterility at the peak of hyperthermia.
• Consultation with narrow specialists - ENT doctor and dentist.
• X-ray of the lungs.

Treatment

Treatment of patients with agranulocytosis is complex, including a number of measures:

1. Hospitalization to the hematology department of the hospital.
2. Placing patients in a boxed ward, where air disinfection is regularly carried out. Completely sterile conditions will help prevent bacterial or viral infection.
3. Parenteral nutrition is indicated for patients with necrotizing ulcerative enteropathy.
4. Thorough oral care involves frequent rinsing with antiseptics.
5. Etiotropic therapy is aimed at eliminating the causative factor - stopping radiation therapy and the administration of cytostatics.
6. Antibiotic therapy is prescribed to patients with purulent infection and severe complications. To do this, two broad-spectrum drugs are used at once - “Neomycin”, “Polymyxin”, “Oletetrin”. Treatment is supplemented with antifungal agents - Nystatin, Fluconazole, Ketoconazole.
7. Leukocyte concentrate transfusion, bone marrow transplant.
8. The use of glucorticoids in high doses - Prednisolone, Dexamethasone, Diprospana.
9. Stimulation of leukopoiesis – “Leukogen”, “Pentoxil”, “Leukomax”.
10. Detoxification - parenteral administration of Hemodez, glucose solution, isotonic sodium chloride solution, Ringer's solution.
11. Correction of anemia - e.g. for iron deficiency anemia: “Sorbifer Durules”, “Ferrum Lek”.
12. Treatment of hemorrhagic syndrome - platelet transfusion, administration of Dicynone, Aminocaproic acid, Vikasol.
13. Treating the oral cavity with Levorin solution, lubricating the ulcers with sea buckthorn oil.

To prevent the development of agranulocytosis, it is necessary to carefully monitor the blood count during treatment with myelotoxic drugs, during radiation therapy and chemotherapy. Such patients need to eat foods that restore bone marrow function. To do this, your diet should include fatty fish, chicken eggs, walnuts, chicken meat, carrots, beets, apples, freshly squeezed vegetable and fruit juices, seaweed, avocados, and spinach. For preventive purposes, you should take vitamins that support the immune system at an optimal level.

The prognosis of agranulocytosis depends on the course of the underlying disease. With the development of septic complications, it becomes unfavorable. The disease can lead to permanent disability and even death of the patient.

Video: about agranulocytosis during chemotherapy

Agranulocytosis is a clinical and laboratory syndrome, the main manifestation of which is a sharp decrease or complete absence of neutrophil granulocytes in the peripheral blood, which is accompanied by an increase in the body’s susceptibility to fungal and bacterial infections.

Granulocytes are the most numerous group of leukocytes, in which, when stained, specific granules (granularity) become visible in the cytoplasm. These cells are myeloid and are produced in the bone marrow. Granulocytes take an active part in protecting the body from infections: when an infectious agent penetrates the tissue, they migrate from the bloodstream through the capillary walls and rush to the site of inflammation, here they absorb bacteria or fungi, and then destroy them with their enzymes. This process leads to the formation of a local inflammatory response.

With agranulocytosis, the body is not able to resist infection, which often becomes a factor in the occurrence of purulent-septic complications.

In men, agranulocytosis is diagnosed 2-3 times less often than in women; People over 40 years of age are most susceptible to it.

Causes

In the autoimmune form of the syndrome, a certain malfunction occurs in the functioning of the immune system, as a result of which it produces antibodies (so-called autoantibodies) that attack granulocytes, thereby causing their death. Autoimmune agranulocytosis can occur against the background of the following diseases:

• autoimmune thyroiditis;
• systemic lupus erythematosus;
• rheumatoid arthritis and other types of collagenosis.

Agranulocytosis is also of an immune nature, developing as a complication of infectious diseases, in particular:

• polio;
• viral hepatitis;
• typhoid fever;
• yellow fever;
• malaria;
• infectious mononucleosis;
• flu

With agranulocytosis, the body is not able to resist infection, which often becomes a factor in the occurrence of purulent-septic complications.

Currently, the hapten form of agranulocytosis is often diagnosed. Haptens are chemical substances whose molecular weight does not exceed 10,000 Da. These include many medications. Haptens themselves do not have immunogenicity and acquire this property only after combining with antibodies. The resulting compounds can have a toxic effect on granulocytes, causing their death. Once developed, hapten agranulocytosis will be repeated every time the same hapten (drug) is taken. The most common causes of hapten agranulocytosis are the drugs Diacarb, Amidopyrine, Antipyrin, Analgin, Aspirin, Isoniazid, Meprobamate, Butadione, Phenacetin, Indomethacin, Novocainamide, Levamisole, Methicillin, Bactrim and other sulfonamides, Leponex, Chloroquine, barbiturates.

Myelotoxic agranulocytosis occurs as a result of a disruption of the process of myelopoiesis that occurs in the bone marrow and is associated with suppression of the production of progenitor cells. The development of this form is associated with the effect on the body of cytostatic agents, ionizing radiation and certain medications (Penicillin, Gentamicin, Streptomycin, Levomycetin, Aminazine, Colchicine). With myelotoxic agranulocytosis in the blood, the number of not only granulocytes, but also platelets, reticulocytes, and lymphocytes decreases, which is why this condition is called a cytotoxic disease.

In order to reduce the risk of infectious and inflammatory diseases, treatment of patients with confirmed agranulocytosis is carried out in the aseptic block of the hematology department.

Forms

Agranulocytosis can be congenital or acquired. Congenital is associated with genetic factors and is extremely rare.

Acquired forms of agranulocytosis are detected with a frequency of 1 case per 1300 people. It was described above that, depending on the characteristics of the pathological mechanism underlying the death of granulocytes, the following types are distinguished:

• myelotoxic (cytotoxic disease);
• autoimmune;
• haptenic (medicinal).

A genuine (idiopathic) form is also known, in which the cause of the development of agranulocytosis cannot be established.

According to the nature of the course, agranulocytosis can be acute or chronic.

Signs

The first symptoms of agranulocytosis are:

• severe weakness;
• pale skin;
• joint pain;
• increased sweating;
• elevated body temperature (up to 39–40 °C).

Characteristic are ulcerative-necrotic lesions of the mucous membrane of the oral cavity and pharynx, which can take the form of the following diseases:

• angina;
• pharyngitis;
• stomatitis;
• gingivitis;
• necrotization of the hard and soft palate, uvula.

These processes are accompanied by spasm of the masticatory muscles, difficulty swallowing, sore throat, and increased salivation.

With agranulocytosis, the spleen and liver become enlarged, and regional lymphadenitis develops.

Features of the course of myelotoxic agranulocytosis

Myelotoxic agranulocytosis, in addition to the symptoms listed above, is characterized by a moderately severe hemorrhagic syndrome:

• formation of hematomas;
• nosebleeds;
• increased bleeding of gums;
• hematuria;
• vomiting mixed with blood or in the form of “coffee grounds”;
• visible scarlet blood in the stool or black, tarry stool (melena).

Diagnostics

To confirm agranulocytosis, a complete blood count and bone marrow puncture are performed.

A general blood test determines severe leukopenia, in which the total number of leukocytes does not exceed 1–2 x 10 9 / L (normal is 4–9 x 10 9 / L). In this case, either granulocytes are not detected at all, or their number turns out to be less than 0.75 x 10 9 / l (the norm is 47–75% of the total number of leukocytes).

When examining the cellular composition of the bone marrow, the following is revealed:

• decrease in the number of myelokaryocytes;
• increase in the number of megakaryocytes and plasma cells;
• impaired maturation and decreased number of neutrophilic germ cells.

To confirm autoimmune agranulocytosis, the presence of antineutrophil antibodies is determined.

If agranulocytosis is detected, the patient should be consulted by an otolaryngologist and dentist. In addition, he needs to undergo a three-time blood test for sterility, a biochemical blood test and a chest x-ray.

Agranulocytosis requires differential diagnosis with hypoplastic anemia, acute leukemia, and HIV infection.

Agranulocytosis can be congenital and acquired, and the first form is an extremely rare phenomenon and is caused by hereditary factors.

Treatment

Treatment of patients with confirmed agranulocytosis is carried out in the aseptic unit of the hematology department, which significantly reduces the risk of infectious and inflammatory complications. First of all, it is necessary to identify and eliminate the cause of agranulocytosis, for example, discontinue the cytostatic drug.

For immune agranulocytosis, high doses of glucocorticoid hormones are prescribed and plasmapheresis is performed. Transfusions of leukocyte mass, intravenous administration of antistaphylococcal plasma and immunoglobulin are indicated. To increase the production of granulocytes in the bone marrow, you need to take leukopoiesis stimulants.

Regular mouth rinses with antiseptic solutions are also prescribed.

If necrotic enteropathy occurs, patients are transferred to parenteral nutrition (nutrients are administered by intravenous infusion of solutions containing amino acids, glucose, electrolytes, etc.).

To prevent secondary infection, antibiotics and antifungal drugs are used.

The prognosis worsens significantly with the development of severe septic conditions, as well as in the case of repeated episodes of hapten agranulocytosis.

Prevention

Without a doctor's prescription and careful hematological monitoring, it is unacceptable to take medications that have a myelotoxic effect.

If an episode of hapten agranulocytosis is recorded, you should not subsequently take the drug that caused its development.

Consequences and complications

The most common complications of agranulocytosis are:

• pneumonia;
• hemorrhage;
• hepatitis;
• sepsis;
• mediastinitis;
• peritonitis.

The prognosis worsens significantly with the development of severe septic conditions, as well as in the case of repeated episodes of hapten agranulocytosis.

Video from YouTube on the topic of the article:

Definition

Agranulocytosis is a clinical and hematological syndrome in which there is a partial or complete disappearance of neutrophils from the peripheral blood.

In 1922, Werner Schulz drew the attention of doctors to a syndrome of unknown etiology, which was observed mainly in middle-aged women and was characterized by severe sore throat, exhaustion, a significant decrease or absolute disappearance of granulocytes from the peripheral blood, the rapid development of sepsis, and led to death. He called this condition agranulocytosis.

The first cases of agranulocytosis were described in Europe and the USA, but the disease is observed in all parts of the world, and amidopyrine is the cause of its occurrence.

The incidence of diseases in women compared to men is 2-3:1.

Causes

Most often, the occurrence of agranulocytosis is associated with the use of medications. If, when using cytostatic agents, the occurrence of neutropenia is an almost natural consequence and is associated with the main mechanism of action, then agranulocytosis due to the use of amidopyrine or aminazine has a different pathogenesis.

There is a lot of information in the literature about the occurrence of agranulocytosis in patients with thyrotoxicosis who used antithyroid drugs such as methylthiouracil, and less commonly, Mercazolil. It has been fully proven that sulfonamides, including antidiabetic ones, have a neutropenic effect, as well as medications such as butadione, phenylbutazone, and heavy metal preparations (bismuth, mercury, arsenic, silver, gold), antihistamines (diprazine), antipsychotic drugs and tranquilizers (aminazine, trioxazine, elenium), barbiturates, novocaine and novocainamide, anticonvulsants (diphenine, trimethine), quinine and its derivatives. Agranulocytic reactions can occur when using most modern antibiotics and anti-tuberculosis drugs.

However, there are cases of agranulocytosis that cannot be clearly associated with exposure to any exogenous factor. It has been suggested that genetic factors are involved in the pathogenesis of this form of agranulocytosis.

Immune agranulocytosis. The concept of the pathogenesis of immune (hapten) agranulocytosis was formulated in the early 50s. Experts have come to the conclusion that leukopenias that occur during allergic conditions are more often associated with the appearance in the body of antibodies (aglutins, lysines, etc.), the action of which is directed against the body’s own leukocytes. It is assumed that medications play the role of haptens, which form complex compounds with proteins circulating in the blood or with proteins of the membrane of leukocytes. Such a complex is “foreign” for the body and is a kind of antigen. Antibodies produced in response to this antigen are fixed on the surface of leukocytes; in addition, direct combination of the antigen in the blood with subsequent adsorption of circulating immune complexes on leukocytes is also possible.

The course of immune agranulocytosis is accompanied by a violation of granulocytopoiesis, the degree of which varies widely. At the height of immune agranulocytosis, bone marrow hypoplasia develops due to the cells of the myeloid lineage. During the recovery period, the bone marrow becomes hyperplastic due to the proliferation of a large number of immature granulocyte cells (promyelocytes and myelocytes).

Immune agranulocytosis can be autoimmune (rheumatoid arthritis, systemic lupus erythematosus, etc.) or associated with the formation of antibodies to exogenous antigens - haptens. Immune agranulocytosis often takes on a cyclically reducing form, especially if it is provoked by an infection (usually viral).

Myelotoxic agranulocytosis. The cause of myelotoxic agranulocytosis is the harmful effects of medications, which leads to a decrease in the proliferative activity of granulocytic lineage cells with the further development of hypoplasia of granulocytopoiesis.

A feature of myelotoxic agranulocytosis is the relationship between the possibility of its occurrence and the total dose of the drug taken, and in each patient this dose does not exceed the therapeutic dose. The development of myelotoxic agranulocytosis may be due to impaired drug metabolism due to enzymatic defects in the liver or other cells involved in the metabolism of drug compounds. In addition, disorders of cellular metabolism are associated with the ability of drugs to increase the permeability of cell membranes and cause precipitation of polynucleotides, which can lead to the inactivation of many enzymes. The interaction of the drug with mitochondrial enzymes causes the uncoupling of oxidative phosphorylation, which results in the suppression of cell proliferative activity and arrest of cells in the G phase. Since the enzymatic systems of granulocytic elements change during the process of differentiation and maturation, the sensitivity to drugs of cells at different stages of differentiation may be different. With maximum damage to the activity of the parent cells, the course of the pathological process will be severe, and aplasia of the granulocytic lineage may be irreversible. With less damage to the stem cell pool, complete revival of the granulocytic lineage and recovery of the patient is possible.

Symptoms

The clinical picture of drug-induced agranulocytosis is characterized by an acute or subacute onset 7-14 days after the first course of taking drugs to which the body is sensitized, or after 1-2 days upon repeated use of these drugs. The disease begins with chills and hyperthermia, arthralgia. The patient is pale, but the mucous membranes retain their normal color, may be cyanotic, and fever appears on the lips. At the same time, granulocytopenia develops, and after 12-24 hours complete agranulocytosis occurs. There is a dirty gray coating on the tonsils. Subsequently, necrotic plaques and ulcers form, which is associated with impaired migration of neutrophils through mucosal surfaces. Spreading, necrotization captures the palatine arches, the uvula, and, of course, the soft and hard palate. Spreading deeper, the necrotic process covers the mucous membrane of the esophagus and intestines and takes on the character of a noma, causing abdominal pain, bloating, nausea, vomiting, and diarrhea (necrotic enteropathy). When deep-lying tissues and blood vessels are destroyed, significant bleeding may occur. In severe cases of agranulocytosis, jaundice may develop due to necrotic processes in the liver. Tissue necrosis can be observed in the kidneys (proteinuria, hematuria, cylindruria), adrenal glands, which leads to acute adrenal insufficiency, and lungs (pneumonia, abscesses, gangrene). Sometimes the ulcerative-necrotic process covers the bladder and female genital organs.

No significant changes are observed in the cardiovascular system, with the exception of hypotension, arterial and venous, and anemic cardiac and vascular murmurs. The spleen is usually not enlarged. Sometimes there is a slight increase in regional lymph nodes, mainly cervical and submandibular. When hemorrhagic syndrome occurs, hematuria appears.

Patients are apathetic, but remain conscious until the agony.

Septicemia poses a major threat to the patient's life. The severity of the infectious complication is determined by the duration of agranulocytosis (the longer the period of agranulocytosis, the more severe the course of the disease and infectious complications). An important element determining the frequency and complexity of infection is the depth of agranulocytosis. In immune and especially hapten-provoked agranulocytosis, there are usually no granulocytes in the blood. In these cases, infectious complications necessarily arise in the first days of the disease. Gram-negative sepsis is often observed, and the source of infection is saprophytic flora - Escherichia coli, Proteus, Pseudomonas aeruginosa. Gram-negative sepsis is accompanied by severe intoxication, hyperthermia up to 40-41°C, a tendency to arterial hypotension, and body hyperemia. With pseudomonas sepsis, small metastatic foci of infection may appear on the skin, which are black in color and the size of which can increase within ten minutes. The same focus can be observed in the lungs, kidneys and other organs during autopsy. These lesions consist of almost pure culture of Pseudomonas aeruginosa.

Diagnostics

Diagnosis of immune agranulocytosis is based on characteristic changes in peripheral blood.

With hapten agranulocytosis, granulocytes and monocytes disappear from the peripheral blood in isolation. Other shaped elements do not change significantly. With a protracted process, sometimes there is slight leukopenia. Exit from agranulocytosis is accompanied by the appearance of plasma cells and single myelocytes in the blood; simultaneously with them, and sometimes the day before, monocytosis occurs. Subsequently, the number of mature granulocytes is rapidly restored. Within a week, the composition of peripheral blood is normalized. Isolated “zeros” of granulocytes are a characteristic sign of hapten agranulocytosis. In addition, pyknosis and nuclear disintegration, toxic granularity and vacuolization of the cytoplasm of the single granulocytes that remain are determined. There are no basophils, sometimes eosinophils are found, ESR is increased.

With autoimmune agranulocytosis, the blood picture is the same, but with it, single granulocytes are more often preserved.

If, with autoimmune agranulocytosis, the number of granulocytes approaches its upper level (750 cells in 1 μl), then there may be no infectious complications for 2-3 weeks. This allows us to consider not 750, but 500 granulocytes in 1 μl as critical. blood.

In both forms of agranulocytosis, the number of leukocytes decreases moderately to 1.5-3.0*10 9 / l due to the preservation of lymphocytes.

Autoimmune agranulocytosis, which complicates the underlying disease, usually manifests itself as a moderate decrease in the number of granulocytes. However, the hematological picture in such cases is influenced by the underlying disease, which can provoke both autoimmune thrombocytolysis and autoimmune lysis of red blood cells. The bone marrow at the height of hapten agranulocytosis does not contain any cells of the granulocytic lineage. At the same time, in trepanati the bone marrow is cellular due to hyperplasia of plasma cells, in addition, megakaryocytosis is observed.

When emerging from agranulocytosis, large bean-shaped or round-nucleated cells appear in the bone marrow, which are slightly larger in size than promyelocytes and contain poor dust-like granules (exit cells).

Differential diagnosis is made between immune agranulocytosis and leukopenic and aleukemic forms of acute leukemia, this is especially necessary in the case of subacute or chronic course of immune agranulocytosis.

Differential diagnosis is based on morphological examination of the bone marrow in agranulocytosis.

Prevention

Therapeutic tactics for both forms of agranulocytosis include, first of all, the fight against infectious complications. In case of hapten agranulocytosis, it is necessary to exclude the use of a drug that may be a hapten. Currently, glucocorticoid hormones are not prescribed for this form of agranulocytosis, since their use leads to an even greater decrease in anti-infective immunity.

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What is agranulocytosis?

Since granulocytes make up a significant portion of the leukocyte count, agranulocytosis invariably occurs with leukopenia. Agranulocytosis is spoken of in cases where the total number of leukocytes does not exceed 1.5 × 109 cells per 1 μl, and granulocytes are either not detected at all or are less than 0.75 × 109 / μl.

Based on the presence of specific granules in the cytoplasm, all leukocytes, which are known to perform a protective function in the body, are divided into:
1. Granulocytes - neutrophils, basophils and eosinophils.
2. Agranulocytes - monocytes and lymphocytes.

Thus, a critical decrease in the concentration of neutrophils, eosinophils and basophils in the blood plasma is called agranulocytosis.

However, eosinophils and basophils (these fractions are mainly involved in allergic inflammation reactions) make up a small percentage of the quantitative composition of all blood leukocytes (1-5% eosinophils and 0-1% basophils), so the figures for critical neutropenia hide the decrease in the concentration of other elements granulocytic series.

In addition, some forms of agranulocytosis - such as, for example, childhood genetically determined agranulocytosis (Kostmann syndrome) - occur with an increase in the number of eosinophils in the blood.

Therefore, the term “agranulocytosis” is often used in the literature as a synonym for critical neutropenia (a critical decrease in the number of neutrophils).

To better understand what agranulocytosis is and what threat it poses to human life, let’s take a short excursion into physiology.

Functions of neutrophils. What danger do they pose?
granulocytopenia and agranulocytosis?

It is neutrophils that mainly ensure complete sterility of the blood. At the same time, they remain in the bloodstream for about 1-3 days, and then migrate into the tissues, where they participate in local protective reactions. The total lifespan of neutrophils is about a week, but in the focus of inflammation they quickly die, making up the main component of pus.

Neutrophils produce a special substance - lysozyme, which has a bacteriostatic (stops the growth and reproduction of bacteria) and bactericidal effect (destroys bacteria), and also promotes the dissolution of damaged areas of body tissue.

In addition, neutrophils produce interferon, a powerful antiviral agent, and activate the initial phase of the complex blood clotting process.

Hapten agranulocytosis occurs when haptens, substances that are harmless in themselves, are involved in immune reactions, but under certain conditions can provoke immune reactions that destroy granulocytes. Drugs most often play the role of haptens, so hapten agranulocytosis is considered as a serious complication of various therapeutic measures.

Genuine agranulocytosis is spoken of in cases where the cause of a sharp decrease in the number of granulocytes in the blood remains unknown.

Causes and pathogenesis of myelotoxic agranulocytosis and leukopenia

Most often, endogenous myelotoxic agranulocytosis is a complication of the following diseases:

• acute leukemia;
• chronic myeloid leukemia in the terminal stage;
• metastases of cancer or sarcoma to the red bone marrow.

The development of exogenous myelotoxic agranulocytosis is due to the fact that, as the most intensively reproducing tissue of the human body, red bone marrow is especially sensitive to many external factors.

The most common causes of exogenous myelotoxic agranulocytosis include:

• exposure to radioactive radiation;
• poisoning with poisons that can suppress hematopoiesis (benzene, toluene, arsenic, mercury, etc.);
• taking myelotoxic medications.

Exogenous myelotoxic agranulocytosis is characterized by the presence of a time interval between the effect of an unfavorable factor on the bone marrow and a critical decrease in the level of granulocytes in the blood.

The duration of this period depends on the nature and strength of the unfavorable factor, and can range from 8-9 days (for example, with severe acute radiation sickness) to weeks, months and even years (chronic poisoning with benzene, mercury, etc.).

Drug-induced myelotoxic agranulocytosis

A number of medications have myelotoxic effects. First of all, these are cytostatics - drugs that inhibit cell division.

These drugs (cyclophosphamide, methotrexate, etc.) are used for oncological diseases, for severe autoimmune pathologies that occur with a high degree of activity (systemic lupus erythematosus, some types of glomerulonephritis, systemic scleroderma, periarteritis nodosa, “sicca” Sjögren’s syndrome, ankylosing spondylitis, etc. .), as well as in transplantology, to prevent rejection of transplanted organs and tissues.

Cytostatics destroy cancer cells, the rate of division of which is many times higher than the rate of reproduction of healthy cells of the body, and have a depressing effect on the pathologically activated immune system, but can cause agranulocytosis due to the suppression of the formation of granulocytes. Therefore, therapy with these drugs is always carried out under constant monitoring of the state of the blood system, and a decrease in the number of leukocytes is an indication for discontinuation of treatment.

Much less often, drug-induced myelotoxic agranulocytosis is caused by drugs that are not used for cytostatic purposes, but can have an adverse effect on the red bone marrow as a side effect. These drugs include chloramphenicol, a broad-spectrum antibiotic, and aminazine, an antipsychotic used for psychotic disorders.

Agranulocytosis caused by drugs with myelotoxic side effects can be combined with anemia and thrombocytopenia due to damage to erythrocyte precursor cells and red blood platelets. In severe cases, pancytopenia develops (a decrease in the number of all cellular elements in the blood).

Causes and pathogenesis of immune agranulocytosis and leukopenia

In this case, antibodies against granulocytes cause cell death not only in the bloodstream and in peripheral depots (spleen, lungs, etc.), but also in the red bone marrow itself. Sometimes the precursor cells of granulocytes are destroyed, so that the mechanism for the development of pathology, in fact, includes a myelotoxic element.

As a result of massive destruction of granulocytes, intoxication syndrome develops - general poisoning of the body with the decay products of dead cells. However, in many cases, the clinical picture of intoxication is blurred by symptoms of infectious complications (in hapten agranulocytosis) or signs of the underlying disease (in the case of autoimmune agranulocytosis).

In all cases of immune agranulocytosis, a specific blood test pattern is observed - the complete disappearance of granulocytes and monocytes while maintaining a close to normal number of lymphocytes. Because of the latter circumstance, the number of leukocytes rarely decreases below 1.5 × 109 cells per 1 μl.

With immune agranulocytosis, concomitant thrombocytopenia and anemia often develop, since antibodies are often formed not only against leukocytes, but also against other cellular elements. In addition, immune damage to the pluripotent progenitor cell in the bone marrow is possible (damage to the cell from which granulocytes, erythrocytes and platelets are subsequently formed).

Features of the pathogenesis of autoimmune agranulocytosis
Autoimmune agranulocytosis itself, in fact, is one of the symptoms of systemic immune disorders, such as systemic lupus erythematosus, rheumatoid arthritis, etc.

The pathogenesis of these diseases is based on the formation of autoantibodies to proteins of the body's own tissues. The causes of these pathologies are not fully understood. Most researchers consider a hereditary predisposition to be proven, and also recognize the role of viral infections and psychological trauma as a trigger.

Autoimmune agranulocytosis usually occurs in young and middle age. Women get sick several times more often than men (the ratio of men to women is 1:3-5, according to various sources) and develops against the background of an extensive clinical picture of the underlying disease, which leaves a certain imprint on its pathogenesis.

So, for example, systemic lupus erythematosus occurs with severe leukopenia, which is an indicator of the activity of the process. Therefore, the course of agranulocytosis in this disease is usually more severe than in other forms of autoimmune agranulocytosis. Thrombocytopenia and even pancytopenia develop more often.

It should be taken into account that in autoimmune diseases, a myelotoxic factor of drug origin may be involved in the pathogenesis of agranulocytosis, since when the process is highly active, patients are often prescribed cytostatics.

Autoimmune diseases have a chronically relapsing course, so agranulocytosis can also become cyclical. Moreover, its course and prognosis largely depend on the curability of the underlying disease.

Causes and pathogenesis of acute hapten agranulocytosis
Hapten agranulocytosis develops due to the deposition of incomplete antigens - haptens, on the surface of granulocyte membranes. The combination of antibodies with haptens located on the surface of leukocytes leads to an agglutination reaction (a kind of gluing) of granulocytes and their death.

As a rule, various medications act as haptens, so hapten agranulocytosis is also called drug-induced or drug-induced agranulocytosis.

Unlike myelotoxic agranulocytosis, which is also caused by certain types of drugs, hapten agranulocytosis begins acutely, often in the first days of taking the drug.

In addition, after cured myelotoxic agranulocytosis, the body becomes more resistant to this type of drug, and in order to cause disorders, a large dose will be needed, and in the case of hapten agranulocytosis, on the contrary, pathological reactions will develop even after extremely low test doses.

Another specific difference between hapten agranulocytosis is its acute nature - with timely discontinuation of the drug that has become a hapten, the number of granulocytes in the blood is restored relatively quickly.

Hapten agranulocytosis can develop at any age, but it occurs extremely rarely in children. It is believed that women develop this complication of drug therapy more often than men, but with age this difference is leveled out.

Statistically, there is a significant increase in cases of hapten agranulocytosis in older age groups. This is due to the fact that in old age people are more likely to suffer from acute and chronic diseases, and therefore are forced to take more medications. In addition, with age, the immune system becomes less flexible and more often fails, both in the direction of a general decrease in immunity and in the direction of the development of pathological immune reactions.

There is evidence that hapten agranulocytosis can be caused by almost any medication. However, there are medications in which such complications occur especially often. These include:

• sulfonamides (including those used to treat type 2 diabetes);
• amidopyrine;
• butadione;
• some anti-tuberculosis drugs (PASK, ftivazid, tubazid);
• procainamide;
• methyluracil;
• antibiotics from the macrolide group (erythromycin, etc.);
• antithyroid drugs (drugs used to treat an overactive thyroid gland).

Features of the pathogenesis of drug-induced agranulocytosis

Drug agranulocytosis can be either myelotoxic (using cytostatics, chloramphenicol and some other drugs) or haptenic (sulfonamides, butadione, etc.).

It should be noted that sometimes the same drug substance causes different types of agranulocytosis in different patients. Thus, at one time, Western doctors published the results of a study of the causes and mechanisms of the development of agranulocytosis when using phenothiazine drugs (aminazine, etc.).

Despite the fact that aminazine is considered a drug that can cause myelotoxic agranulocytosis in individuals with idiosyncrasy (with special sensitivity to the drug), in many patients, using special antibody tests, the immune nature of agranulocytosis was revealed.

In some cases, the destruction of granulocytes was caused by the presence of specific antibodies, which were quickly washed out of the body, just as with hapten agranulocytosis. In such patients, the clinical picture of drug-induced agranulocytosis developed quickly and rapidly, but stopping the drug gave a fairly quick positive result.

Other patients developed an autoimmune reaction with the formation of antibodies to the protein elements of the nuclei of leukocytes, as happens, for example, with systemic lupus erythematosus. Of course, in such cases, agranulocytosis developed gradually and tended to be chronic.

Thus, the mechanism of development of drug-induced agranulocytosis depends not only on the nature of the drug, but also on many other factors, such as the gender and age of the patient, the state of his immune system, the presence and severity of concomitant diseases, etc.

Some drugs that often cause
drug-induced agranulocytosis

Some antirheumatic drugs that can cause hapten agranulocytosis

As a rule, clinical signs of the disease develop three months after starting the drug. Often, the classic symptoms of agranulocytosis are preceded by skin rashes.

Hapten agranulocytosis is a side effect allopurinol– a drug taken for gout. This complication is more common in middle-aged and elderly people. Cases of the development of agranulocytosis in young people have been described when allopurinol was taken against the background of complete fasting.

Some antibacterial drugs that often cause drug-induced
agranulocytosis

However, agranulocytosis and leukopenia can be complications of taking many antibiotics. Cases of the development of agranulocytosis have been described with long-term use of large doses of penicillin antibiotics and related cephalosporins. In this case, pathological symptoms occurred 2-3 weeks after the start of taking the drugs.

The connection between hapten agranulocytosis and the intake of sulfonamides has been known for a long time. Most often, complications when taking sulfonamides develop in elderly and senile women. The combination drug Biseptol is considered especially dangerous.

Risk of developing drug-induced agranulocytosis when taking antipsychotics, antidepressants and anticonvulsants

A characteristic symptom of agranulocytosis is the rapid formation of ulcers. In this case, the process of necrotization spreads to neighboring surfaces, and often takes on the character of a noma (the so-called water cancer - the transition of an ulcerative-necrotic process to the mucous membrane of the cheeks with the development of gangrene of facial tissues).

Similar inflammatory processes occur in the gastrointestinal tract. Here, ulcerative-necrotic enteropathy specific to agranulocytosis develops, which is characterized by the formation of necrosis of the mucous membrane of the esophagus, stomach and intestines.

Clinically, this is manifested by bloating and severe cramping pain in the abdomen, vomiting and diarrhea, sometimes with blood. With deep necrotic lesions of the digestive tract, severe bleeding occurs that threatens the patient’s life. In severe cases, jaundice may develop due to an infectious liver lesion. Perforation of formed ulcers with the development of a clinical picture of an acute abdomen is rare.

Often, with agranulocytosis, inflammation of the lungs occurs, which takes an atypical course with a tendency to form large abscesses (abscesses), develop gangrene and spread the process to neighboring organs.

Damage to the lungs is manifested by cough, shortness of breath, and when the process moves to the pleura - pain in the chest when breathing. In severe cases, acute respiratory failure may develop.

Much less often, with agranulocytosis, the infectious process begins from below, covering the genitourinary organs (urethra, bladder, uterus and vagina in women). In this case, patients complain of pain and pain during urination, urinary retention, and pain in the lower abdomen. Women may experience itching and abnormal vaginal discharge.

As a result of intoxication, arterial and venous hypotension develops, and functional murmurs are heard on auscultation of the heart. On the part of the kidneys, albuminuria (protein excretion in the urine) is noted, associated with a reaction to infectious processes. In cases where the infectious process through the urinary system spreads to the kidneys, blood, protein, and epithelial cells of the renal tubules are detected in the urine.

Symptoms of septic complications with agranulocytosis

Most characteristic of agranulocytosis is the development of so-called gram-negative sepsis - blood infection caused by saprophytic (that is, under normal conditions not exhibiting any pathogenic properties) intestinal flora - Proteus, Pseudomonas aeruginosa and Escherichia coli.

This pathology is extremely difficult, with high hyperthermia (41-42 degrees), severe intoxication and rapid dissemination of infection throughout the body. Particularly characteristic is the appearance of lesions on the skin, which are black rashes that increase in size over ten to fifteen minutes. The same lesions appear in the lungs, liver, kidneys and other organs.

The course and prognosis of acute and chronic agranulocytosis

In the acute course of agranulocytosis, the prognosis depends on the degree of decrease in the concentration of granulocytes, the initial state of the body and the timeliness of specialized medical care.

In the case of chronic agranulocytosis, the prognosis is mainly determined by the course of the underlying disease (systemic lupus erythematosus, chronic mercury poisoning, acute leukemia, etc.).

Treatment

Complex treatment

In each specific case, the origin of agranulocytosis, the degree of its severity, the presence of complications, and the general condition of the patient (gender, age, concomitant diseases, etc.) are taken into account.

If necessary, according to standard regimens, detoxification therapy is prescribed, anemia, hemorrhagic syndrome and other related disorders are corrected.

Etiotropic treatment

If you suspect drug-induced agranulocytosis caused by drugs that do not have a direct myelotoxic effect, you should immediately stop taking them.

In case of timely discontinuation of the drug that caused a decrease in the level of granulocytes, a fairly rapid restoration of the normal state of the peripheral blood is possible.

Creating conditions of complete sterility in acute agranulocytosis

Treatment and prevention of infectious complications in agranulocytosis

Preventive antibiotic therapy is carried out when the level of leukocytes decreases to 1 × 109 cells per 1 μl or lower. In the presence of diabetes mellitus, chronic pyelonephritis or other serious foci of internal infection, prophylactic administration of antibiotics is also prescribed at higher levels of leukocyte concentration in the blood (1 - 1.5 × 109 cells per 1 μl).

As a rule, 1-2 broad-spectrum antibiotics are used for prophylaxis in medium doses, intravenously or intramuscularly.

To treat infectious complications of agranulocytosis, 2-3 broad-spectrum antibiotics are used in maximum doses, which are administered orally (intravenously or intramuscularly). In addition, as a rule, non-absorbable (not absorbed into the blood) antibiotics are prescribed for oral administration to suppress intestinal microflora.

Therapeutic and prophylactic antibiotic therapy is carried out until the state of agranulocytosis emerges. In this case, the course of treatment is supplemented with antifungal drugs (nystatin, levorin).

Immunoglobulin and antistaphylococcal plasma are often used in complex therapy for agranulocytosis.

Leukocyte transfusion

Treatment with glucocorticoids

Stimulation of leukopoiesis

Agranulocytosis in children

Agranulocytosis in children with Kostmann syndrome: causes, symptoms, treatment

In some cases, the pathology is combined with mental retardation, microcephaly (small head size) and short stature.

The mechanism of development of agranulocytosis is not fully understood. It has been established that neutropenia is caused by impaired maturation of neutrophil precursor cells. However, what exactly causes the defect is still unknown.
with the formation of abscesses in the liver.

The leukocyte formula in Kostmann syndrome undergoes specific changes. Typical cases are characterized by extreme neutropenia (neutrophils may not be detected at all), eosinophilia and monocytosis with a normal number of lymphocytes.

Until recently, the prognosis for Kostmann syndrome was very unfavorable, especially in the neonatal period (with age, the manifestations of agranulocytosis become less pronounced), but recently treatment with granulocyte colony-stimulating factor (G-CSF) has shown encouraging results.

This drug, originally isolated from mouse plasma, stimulates the proliferation of granulocyte stem cells, increases the rate of their maturation and, according to some data, improves the quality of maturing neutrophils.

Agranulocytosis in children with cyclic neutropenia

This pathology is characterized by rhythmic fluctuations in the level of neutrophils in the blood - from a normal number to deep agranulocytosis (may not be detected in peripheral blood).

The mechanism of development of the pathology is still not clear; a genetically determined defect in neutrophil precursor cells is assumed.

Cyclically occurring agranulocytosis is characterized by attacks of recurrent fever with ulcerative lesions of the oral cavity and pharynx, accompanied by enlarged regional lymph nodes and severe symptoms of intoxication.

After an attack of fever, the patient’s condition returns to normal, but some patients experience complications due to the development of otitis media, abscess pneumonia, etc.

The most significant diagnostic sign of cyclic neutropenia is a periodically appearing decrease in the number of blood granulocytes. During the febrile period, as a rule, agranulocytosis is observed for 3-4 days, then neutrophils are found in the blood, but in reduced numbers. Often during this period there is an increase in the number of lymphocytes.

After the end of the neutropenia phase, laboratory tests register transient monocytosis and eosinophilia. Then, before the start of the next cycle, all indicators completely return to normal.

In 70% of patients, a decrease in granulocytes occurs after 21 days, and lasts from 3 to 10 days (the degree of impairment usually correlates with the duration of neutropenia). However, there are also shorter (14 days) and longer (28-30 days) “light intervals”.

In some cases, the cyclic appearance of agranulocytosis is accompanied by a decrease in the number of red blood cells and platelets.

Treatment of agranulocytosis with cyclic neutropenia consists, first of all, in the prevention of infectious complications. Administration of granulocyte colony-stimulating factor (G-CSF) reduces the severity of granulocytopenia, but does not completely eliminate cyclic changes.

The prognosis is relatively favorable, since with age the clinical manifestations of agranulocytosis with cyclic neutropenia significantly soften.

Granulocytopenia and agranulocytosis of newborns with isoimmune conflict

The mechanism for the development of agranulocytosis in isoimmune neutropenia is based on the formation by the mother of antibodies to the child’s granulocytes, which have an antigenic composition received from the father. Typically, antibodies are directed against granulocyte precursor cells in the red bone marrow.

A feature of agranulocytosis in isoimmune conflict is its transit nature - the mother’s antibodies are quite quickly washed out of the body, and spontaneous normalization of the number of granulocytes in the baby’s blood occurs. Full recovery usually occurs 12-20 weeks after birth.

Therefore, treatment tactics consist of combating infectious complications using standard antibiotic therapy.

Blood tests are performed for almost every pathology. This is due to the information content of this analysis. By changes in individual blood parameters, one can judge the etiology of the disease and the severity of the pathological process. Information about the increase or decrease of certain specific plasma cells allows one to suspect specific disorders. For example, leukemia, various types of anemia. One of the laboratory signs is agranulocytosis. This is a syndrome that can occur alone or in combination with other changes in the composition of the blood. This sign indicates the presence of a severe infectious process.

Agranulocytosis - what is it?

The science of hematology deals with blood diseases. A disorder that indicates a severe pathological process is agranulocytosis. This is a syndrome characterized by a pronounced decrease in the level of white blood cells - leukocytes. They are necessary to combat infectious agents that enter the body during infection.

The normal number of leukocytes in the blood is 4-9 * 10 9 / l. An increase in the number of these cells indicates the development of an inflammatory focus. A lack of white blood cells can occur due to insufficiency of the immune system, inhibition of hematopoiesis, and intoxication. Agranulocytosis is a laboratory syndrome characterized by a decrease in the level of leukocytes to 1 * 10 9 / l or less (neutrophils - 0.75 * 10 9). Due to a pronounced deficiency of immune cells, various infectious processes of bacterial or viral etiology arise. To identify this syndrome, a clinical blood test is necessary.

Incidence of agranulocytosis

This hematological syndrome occurs among female and male populations. Congenital agranulocytosis is recorded less frequently compared to acquired disease. Middle-aged women (over 40 years old) are more susceptible to such changes in the cellular composition of the blood. The frequency of occurrence of this laboratory sign differs in different countries. On average, agranulocytosis is detected in 1 in 1,200 people. Caucasians are more susceptible to a significant decrease in the number of leukocytes.

Reasons for the development of agranulocytosis

Why does agranulocytosis develop? The causes of this pathological condition depend on the type of disease. Congenital agranulocytosis is caused by a hereditary factor. The syndrome refers to genetically determined pathologies. The risk that a child born from a sick mother or father will have this syndrome is very high. The causes of acquired agranulocytosis include the following:

It is worth noting that agranulocytosis is not an independent pathology. This syndrome cannot develop without a specific cause. It is always associated with some kind of pathological effect.

Mechanism of development of agranulocytosis

Neutrophils are protective blood cells. They are formed in the bone marrow and are released in large quantities constantly. These cells make up about 70% of the total number of leukocytes. With insufficient production of these blood elements, neutropenia develops. Agranulocytosis is considered an advanced form of this condition. Congenital deficiency of neutrophils, as well as the total number of leukocytes, occurs due to the presence of a pathological gene.

As a result of exposure to exogenous factors, the production of white blood cells decreases or stops completely. Another mechanism for the development of the syndrome is the production of antibodies to neutrophils. Thus, agranulocytosis occurs. Blood tests will change almost immediately. After all, the life span of neutrophils is quite short. It ranges from 2 to 3 days.

Classification of pathological conditions

Depending on the cause and pathogenetic mechanism, there are several classifications of agranulocytosis. According to this, congenital and acquired neutrophil deficiency are distinguished. In the first case, this hematological syndrome occurs with the following genetic pathologies:

1. Granulomatous disease.
2. Familial neutropenia.
3. Shwachman-Diamond syndrome.
4. Kostmann's disease.
5. Shediac-Steinbrink-Higashi syndrome.
6. Congenital aleukia.

Acquired white blood cell deficiency is divided into autoimmune, myelotoxic and hapten agranulocytosis. Each of these forms has its own development mechanism. According to the course of the pathological process, acute conditions and chronic agranulocytosis are distinguished. The classification is also based on the severity of the syndrome.

Description of immune agranulocytosis

Immune agranulocytosis is associated with the pathological effect of antibodies on blood cells. It can be caused by both endo- and exogenous mechanisms. In the first case, the disease occurs due to autoimmune aggression. This condition leads to systemic pathologies of connective tissue. The cells of the immune system do not change in composition, but they are, as it were, “reprogrammed.” As a result, they begin to oppose the body's own tissues. Granulocytes quickly mature and are destroyed on their own. however, they do not matter. Immune agranulocytosis syndrome occurs in pathologies such as systemic lupus erythematosus and rheumatoid arthritis. In this case, the deficiency of neutrophils is combined with a deficiency of other blood cells.

Another type of disease that occurs against the background of immune processes is hapten agranulocytosis. In this form of the pathological process, antibodies to neutrophils are also formed. The difference is that they are not produced independently, but after taking certain medications - haptens. Repeated intake of these substances causes an immune reaction, expressed in the destruction of granulocytes. Some antibacterial drugs, hypoglycemic and anti-inflammatory drugs, and barbiturates can act as haptens.

Description of myelotoxic agranulocytosis

Myelotoxic agranulocytosis develops as a result of exogenous influences. It is always combined with erythro- and thrombocytopenia. In most cases, the myelotoxic variant of the disease is associated with exposure to chemotherapy drugs and ionizing radiation. These factors lead to inhibition of hematopoiesis at the initial levels of its development. Cytostatic drugs that cause a similar reaction include cyclophosphamide, fluorouracil, mercaptopurine, etc. Inhibition of hematopoietic precursor cells leads to a decrease in the number of granulocytes in the bone marrow. This occurs due to impaired maturation of blood sprouts.

In addition to exogenous influences, a deficiency of hematopoietic cells develops in some types of anemia and leukemia. These reasons often cause agranulocytosis in children. Often hematological changes are hereditary. Examples include hemolytic and aplastic anemia. Acute and chronic myeloblastic leukemia develops both in childhood and among the adult population.

Agranulocytosis: symptoms of the disease

Granulocyte deficiency is accompanied by severe clinical manifestations. They can be different, depending on the underlying disease that led to the neutrophil deficiency. How does agranulocytosis manifest? Symptoms of pathology:

1. Severe general weakness.
2. High fever.
3. Lymphadenopathy.
4. Hepatosplenomegaly.
5. Necrotic changes in the mucous membranes.

Hapten agranulocytosis, unlike other forms, is characterized by an acute course. Patients quickly feel worse, develop fever, and develop mouth ulcers. Damage to the gums, tonsils, uvula, and soft palate progresses, leading to tissue necrosis. This is accompanied by pain, inability to swallow,

With the myelotoxic variant of agranulocytosis, bleeding often develops. They are associated not only with ulceration of the mucous membranes, but also with platelet deficiency. Nasal, gingival, uterine, and gastrointestinal bleeding are noted. Hematomas appear on the skin. Due to ulcerative-necrotic processes in the intestines, diarrhea and abdominal pain are noted. As a result of blood aspiration, hemorrhagic pneumonia develops.

Changes in tests for agranulocytosis

Often the development of agranulocytosis occurs in patients with cancer, systemic and severe infectious diseases. This syndrome can be suspected based on symptoms such as high fever, weakness and the appearance of ulcers in the mouth. Congenital agranulocytosis is more difficult to diagnose. A blood test must be performed if the child has severe pale skin or hemorrhagic manifestations. The study noted a decrease in leukocytes (less than 1*10 9 /l). This is often combined with anemia and thrombocytopenia.

To find out why this hematological syndrome developed, an immunogram and bone marrow puncture are performed. To diagnose complications caused by granulocyte deficiency, instrumental studies are performed. Among them are chest radiography and colonoscopy. Consultations with specialists are also required - otolaryngologist, oncologist, dentist, rheumatologist and gastroenterologist.

Pathology treatment methods

Hospitalization of the patient is necessary if agranulocytosis is detected. Treatment consists of treating ulcerative-necrotic surfaces with antiseptic agents and ointment preparations. To prevent the patient from being subjected to secondary infection, he is placed in an isolation ward. If the intestinal mucosa is damaged, nutrition is provided parenterally.

Medicines for the treatment of agranulocytosis

To prevent the development of an infectious process (pneumonia, sepsis), antibiotics and antifungal medications are prescribed. In particular, leukocyte mass is injected intravenously. For immune agranulocytosis, hormonal medications are indicated. These include the drugs "Hydrocortisone", "Prednisolone". If the syndrome is caused by inhibition of hematopoiesis, stimulants are administered. Among them are the solution “Granocyte”, “Leukogen”, “Virudan”. Treatment is carried out in the hematology department.

Prevention of agranulocytosis in children and adults

Prevention of congenital agranulocytosis includes early detection of the disease. For this purpose, children undergo a clinical blood test annually. Preventive measures include monitoring patients taking cytostatics and anti-tuberculosis hypoglycemic agents. If the patient has previously experienced a hematological reaction to the administration of certain drugs, then these medications cannot be re-prescribed.

Prognosis for life with agranulocytosis

The prognosis depends on the cause of the syndrome. The most dangerous form is hapten agranulocytosis, since tissue necrosis quickly develops in it. Autoimmune and myelotoxic damage can be treated through replacement therapy. An unfavorable prognosis is observed with the development of complications of the underlying pathology. Among them are massive bleeding, perforation of the intestinal wall, hemorrhagic pneumonia, and sepsis.