Agranulocytosis

Leukocytes, as everyone knows, are necessary for the body as protectors from various foreign bodies that enter the blood and can cause various diseases. The state of a person's immunity directly depends on the number of leukocytes in his blood.

Agranulocytosis is a severe pathological condition of the blood, characterized by a decrease in the level of leukocytes in the blood due to the number of granulocytes, which are the most important fraction of the leukocytes mentioned above.

If the level of leukocytes in the blood plasma decreases to 1.5x10 ⁹ per μl of blood, and granulocytes - to 0.75x10 ⁹ per the same μl of blood, then in this case we can talk about the occurrence of agranulocytosis. Granulocytes are represented by such blood components as neutrophils, basophils and eosinophils. Other particles of leukocytes are called agranulocytes. And they include monocytes and lymphocytes. But it is worth noting that the percentage of such granulocytes as eosinophils and basophils in the blood serum is quite low. Therefore, their decrease may not affect the occurrence of this disease. In addition, in some forms of agranulocytosis, an increase in the level of eosinophils in the blood plasma is detected. Therefore, agranulocytosis is often called such a synonym as critical neutropenia, which is characterized by a critical decrease in the level of neutrophils in the blood serum.

Pathological processes in this disease look like this. In a healthy organism, bacteria and other microflora, inhabiting it in excess, peacefully coexist with the "host". There are cases of symbiosis of bacteria and humans for the production of substances useful to the body. For example, the production of vitamin K in the intestinal tract, the suppression of pathogenic microflora, and so on. Of the leukocytes, mainly granulocytes do not allow pathogenic microorganisms to multiply and spread. But with a decrease in the number of the above-mentioned blood particles, the body no longer has the ability to restrain the spread of various pathogenic bacteria and fungi. This fact leads to the emergence of infectious diseases of various nature and the occurrence of complications.

[ 1 ], [ 2 ], [ 3 ]

Causes of Agranulocytosis

The causes of agranulocytosis are quite compelling. Such a serious disease does not just happen, as they say.

So, the prerequisites that can lead to pathological changes in the blood include:

• Exposure to ionizing radiation and radiotherapy.
• Ingestion of chemicals such as benzene.
• The effects of insecticides - substances used to kill insects.
• Consequences of using some drugs that directly inhibit hematopoiesis. Such drugs include the influence of cytostatics, valproic acid, carmazepine, beta-lactam antibiotics.
• Consequences of using medications that act on the body as haptens - substances that are not able to stimulate the production of antibodies to them in humans, and therefore trigger immune processes. Such drugs include gold-based drugs, antithyroid drugs, and others.
• Some autoimmune diseases in a person's medical history. It is known to influence the process of agranulocytosis, lupus erythematosus and autoimmune thyroiditis.
• The entry of certain infections into the human body, such as the Epstein-Barr virus, cytomegalovirus, yellow fever, and viral hepatitis. The appearance of these diseases is accompanied by moderate neutropenia, but some people may develop agranulocytosis.
• Infections present in the body in a generalized form that affect many organs and tissues of a person. The nature of the occurrence of infectious processes can be both viral and bacterial.
• Severe degree of emaciation.
• A person's history of genetic disorders.

[ 4 ], [ 5 ], [ 6 ], [ 7 ]

Symptoms of agranulocytosis

Agranulocytosis usually manifests itself in infectious processes in the body that are caused by microorganisms such as bacteria and fungi.

Symptoms of agranulocytosis are as follows:

• General signs of the disease are expressed in:
  • fever,
  • weaknesses,
  • sweating,
  • shortness of breath,
  • increased heart rate.
• Specific signs of the disease depend on the inflammation site and the type of infectious agent. Therefore, a person who has a history of this dysfunction may experience necrotic tonsillitis, pneumonia, skin lesions, etc.
• If thrombocytopenia develops with agranulocytosis, the person begins to suffer from increased tissue bleeding.
• First of all, infectious lesions begin to affect the oral cavity of a person, because there is a large amount of pathogenic microflora in it. With a low content of granulocytes in the blood, the patient, first of all, begins to have various problems with the oral cavity, which manifest themselves in:
  • stomatitis - inflammatory processes of the oral mucosa,
  • gingivitis - inflammatory processes in the gums,
  • tonsillitis - inflammatory processes in the tonsils,
  • pharyngitis – inflammatory processes of the larynx.

It is known that with this disease, leukocytes are not inclined to get into the foci of infection. Therefore, the affected area is covered with fibrous-necrotic tissue. On the surface of the localization of infection, a dirty-gray coating can be found, and bacteria begin to multiply vigorously under it. Due to the fact that the mucous membrane of the oral cavity is abundantly supplied with blood, toxins from the vital activity of bacteria enter the blood. And then, with the help of the general blood flow, they are carried throughout the patient's body, causing symptoms of general intoxication in a severe stage. Therefore, the patient develops a high fever, accompanied by a temperature of about forty degrees and above. Weakness, nausea and headache also appear.

Read more about the symptoms of agranulocytosis here.

Diagnosis of agranulocytosis

Diagnosis of agranulocytosis involves the following measures:

• General blood test, as well as urine and feces.
• A blood test in which it is important to determine the level of reticulocytes and platelets.
• Taking a sternal puncture and studying the myelogram.
• Obtaining data on blood sterility, which are taken repeatedly, at the peak of fever manifestation. It is important to study the sensitivity of pathogenic flora to antibiotics.
• Blood biochemistry tests that can determine the amount of total protein and protein fractions, sialic acids, fibrin, seromucoid, transaminase, urea and creatine.
• Undergoing an examination by an otolaryngologist.
• Undergoing a dental examination.
• Conducting an X-ray examination of the lungs.

The results of a general blood test, which can diagnose agranulocytosis, will be discussed below. But other indicators should show the following picture:

• in bone marrow studies - a decrease in the level of myelokaryocytes, impaired function of granulocyte maturation, characterizing different stages of cell development, an increased number of plasma cells.
• in a general urine analysis – the presence of proteinuria (transient) and cylindruria.

[ 8 ], [ 9 ], [ 10 ], [ 11 ], [ 12 ], [ 13 ], [ 14 ], [ 15 ]

Blood test for agranulocytosis

In agranulocytosis, a general blood test is an important laboratory test. The presence of this disease may be indicated by such results as an increase in ESR, the presence of leukopenia and neutropenia, which may even be characterized by the complete disappearance of granulocytes. The number of granulocytes is less than 1x10 ⁹ cells per µl of blood. The clinical picture of the disease is also characterized by the occurrence of some lymphocytosis. Sometimes anemia is noted, that is, a reduced content of red blood cells. Thrombocytopenia and / or monocytopenia may also occur. An important factor in establishing a diagnosis is the detection of plasma cells in the blood, about one or two percent.

Biochemical blood tests (BBC) show that gammaglobulins, sialic acids, fibrin and seromucoid are present in increased amounts.

[ 16 ], [ 17 ], [ 18 ], [ 19 ], [ 20 ], [ 21 ], [ 22 ], [ 23 ], [ 24 ]

Treatment of agranulocytosis

For such a serious disease as agranulocytosis, complex treatment is necessary. It is important to take a number of measures, which include the following points:

• Finding out the cause of the pathology and its elimination.
• Creating optimal conditions for the patient to recover, which include complete sterility.
• Taking preventive measures against the occurrence of infectious infections, as well as therapy for existing infections and their complications.
• Undergoing the procedure of leukocyte mass transfusion.
• Prescription of steroid therapy.
• Undergoing procedures that stimulate leukopoiesis.

It is important to understand that the treatment of agranulocytosis requires an individual approach in each specific case. Specialists take into account many factors that can influence the treatment regimens for the disease. These factors include:

• the cause of the disease and the nature of its origin,
• degree of disease progression,
• existing complications,
• patient's gender,
• age of the patient,
• history of concomitant diseases associated with the underlying disease.

In parallel with the treatment of the underlying problem, it is recommended to use the following treatment regimens:

• If such a need arises, then detoxification therapy may be prescribed, which is carried out in a standard manner.
• According to indications, the patient is treated for anemia.
• If symptoms are present, the patient receives therapy for hemorrhagic syndrome.
• It is possible to have a corrective effect on other actualized problems.

Let us consider in more detail the methods of treating agranulocytosis that are available in practice:

• If the patient has a pronounced degree of leukopenia together with agranulocytosis, then this complex of problems is an indication for the use of etiotropic treatment. Such therapy consists of canceling radiotherapy sessions and using cytostatics. Patients who have received a sharp decrease in leukocytes due to taking drugs that do not have a direct myelotoxic effect, with drug-induced agranulocytosis should stop taking these drugs. In this case, if the drugs were canceled in a timely manner, there is a high chance of rapid restoration of the level of leukocytes in the blood.
• Acute agranulocytosis requires placing the patient in conditions of complete sterility and isolation. The patient is placed in a sterile box or ward, which helps prevent his contact with the external environment to prevent infection with various infections. Regular quartz sessions should be held in the room. Visits from relatives of the patient are prohibited until the patient's blood condition improves.
• In this condition of the patient, the attending staff conducts therapy and prevention of infectious complications. In this case, antibacterial drugs are used that do not have a myelotoxic effect. Such therapy is indicated if the level of leukocytes in the blood is reduced to 1x10 ⁹ cells per μl of blood and, of course, at lower rates. There are also some nuances in the correction of certain conditions: diabetes mellitus, chronic pyelonephritis and other foci of infectious processes require the use of antibiotics as a preventive measure and at a higher level of leukocytes in the blood - about 1.5x10 ⁹ cells per μl of blood.

In infectious therapy, as a preventive measure, specialists use one or two antibacterial drugs, which are given to the patient in an average dosage. The drugs are administered intravenously or intramuscularly, depending on the form of the drug.

In the presence of serious infectious complications, two or three antibiotics are used, which have a broad spectrum of action. In this case, the doses are prescribed maximum, the drugs are administered orally, as well as intravenously or intramuscularly.

To suppress the proliferation of pathogenic intestinal flora, in most cases, non-absorbable (which are not absorbed into the blood) antibiotics are prescribed.

Also sometimes the parallel use of antifungal medications is prescribed, for example, Nystatin and Levorin.

Complex therapy involves fairly frequent administration of immunoglobulin and antistaphylococcal plasma preparations.

All the above anti-infective measures are used until the patient's agranulocytosis disappears.

• Methods of transfusion of leukocyte mass. This method of therapy is indicated for those patients who do not have antibodies to leukocyte antigens. At the same time, specialists try to avoid cases of rejection of the injected mass by the body. For these purposes, they use the HLA-antigen system, which allows checking the compatibility of the patient's leukocytes with the leukocytes of the injected drug.
• Glucocorticoid therapy. The indication for this type of medication is immune agranulocytosis. The effectiveness of this treatment is due to the fact that glucocorticoids have an inhibitory effect on anti-leukocyte antibodies, or rather, on their production. Also, drugs of this group have the ability to stimulate leukopoiesis. According to the standard scheme, Prednisolone is used in this case, which is indicated for use from forty to one hundred milligrams per day. The dose is gradually reduced after blood counts show the process of improvement of the patient's condition.
• Stimulation of leukopoiesis. Such a measure is required in myelotoxic and congenital agranulocytosis. Modern medical practice notes the rather successful use of granulocyte colony-stimulating factor (G-CSF).

Prevention of agranulocytosis

Prevention of agranulocytosis can be expressed in the following actions:

• Using procedures that replenish the number of white blood cells in the blood. These procedures include therapy with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF).
• It is important to include in the regimen for preventing the loss of leukocytes medications that stimulate their production and prevent the disappearance of these particles.
• It is necessary to establish a diet that would include a large number of products that promote the restoration of bone marrow function and the production of leukocytes. It is useful to diversify your diet with fatty fish, chicken eggs, walnuts, chicken meat, carrots, beets, apples, and better yet, juices and juice mixtures from these riches of nature. It is also important to include seaweed, avocado, peanuts and spinach in the patient's menu.

Prognosis of agranulocytosis

The prognosis for agranulocytosis in adults with various types of the disease is as follows:

• In acute agranulocytosis, the efficiency and correctness of medical care for the patient are of great importance. The possibility of recovery, as well as the prevention of infectious complications, depend on this. An important point is also the number of granulocytes in the blood, determined after a laboratory study. No less a determining factor that affects a favorable prognosis is the initial state of health of a person before the pathology occurred.
• In the chronic form of the disease, the prospects for recovery are determined by the course of the underlying disease that caused this pathological condition.

The prospects for recovery in childhood forms of the disease are as follows:

• The prognosis for Kostmann syndrome (infantile genetically determined agranulocytosis) has so far been extremely unfavorable. Especially for newborns, the presence of the disease foreshadowed a fatal outcome. But recently, granulocyte colony-stimulating factor (G-CSF) has proven itself as a therapy.
• In agranulocytosis against the background of cyclic neutropenia in children, the prognosis is relatively favorable. Since age-related changes soften the nature of the disease.
• Agranulocytosis in newborns with isoimmune conflict goes away on its own within ten to twelve days from the moment of birth of the baby. At the same time, it is important to prevent the development of infectious complications, which is expressed in correctly applied antibacterial therapy.

Agranulocytosis is a serious blood disease that leads to equally serious complications of an infectious nature. Therefore, for a favorable outcome in this pathology, it is important to start appropriate treatment in time, as well as to follow all the recommendations of specialists.