Agranulocytosis

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

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

If the level of leukocytes in the blood plasma decreases to 1.5x10 ⁹ per 1 μl of blood, and the granulocyte counts to 0.75 × ^{10 9} per same μl of blood, then in this case it can be said about the appearance of agranulocytosis. Granulocytes are represented by such components of blood 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 serum content of such granulocytes as eosinophils and basophils is low enough. Therefore, their reduction may not affect the appearance of this disease. In addition, with some forms of agranulocytosis, there is an increase in the level of eosinophils in the blood plasma. Therefore, agranulocytosis is often referred to as a synonym for critical neutropenia, which is characterized by a critical decrease in the level of neutrophils in serum.

Pathological processes in this disease are as follows. In a healthy organism, bacteria and other microflora, in excess of its population, peacefully coexists with the "master." There are cases of symbiosis of bacteria and humans for the production of substances useful to the body. For example, the development of vitamin K in the intestinal tract, the oppression of pathogenic microflora and so on. Of the leukocytes, mainly granulocytes do not allow multiplying and spreading to pathogens. But with a decrease in the number of the above-mentioned blood particles, the organism no longer has the ability to contain the spread of various pathogenic bacteria and fungi. This fact leads to the emergence of infectious diseases of various types and the occurrence of complications.

[1], [2], [3], [4], [5]

Causes of agranulocytosis

The causes of agranulocytosis are quite weighty. It's just that, as they say, such a serious illness does not arise.

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

• The effects of ionizing radiation and radiation therapy.
• The ingestion of chemicals such as benzene.
• Impact of insecticides - substances used to kill insects.
• The consequences of the use of certain drugs that directly oppress hemopoiesis. These drugs include the effects of cytostatics, valproic acid, carmazepine, beta-lactam antibiotics.
• The consequences of using medications that act on the body, like haptens - are substances that can not stimulate a person to produce antibodies to them, and consequently launch immune processes. To the same drugs include drugs based on gold, drugs of the antithyroid group and others.
• Available in the history of man some diseases of autoimmune nature. The influence on the process of agranulocytosis of lupus erythematosus and autoimmune thyroiditis is known.
• The ingress of certain infections into the human body, for example the Epstein-Barr virus, cytomegalovirus, yellow fever, viral hepatitis. The appearance of these diseases accompanies neutropenia in a moderate stage, but some people may have agranulocytosis.
• The infections in the body in the generalized form that affect many organs and tissues of a person. The nature of the emergence of infectious processes can be both viral and bacterial.
• A strong degree of emaciation.
• There are violations of genetic origin in a person's anamnesis.

[6], [7], [8], [9]

Symptoms of agranulocytosis

Agranulocytosis, as a rule, manifests itself in infectious processes in the body, which are caused by microorganisms such as bacteria and fungi.

Symptoms of agranulocytosis are as follows:

• Common signs of the disease are expressed in:
  • fever,
  • weakness,
  • sweating,
  • shortness of breath,
  • increased heart rate.
• Specific signs of the disease depend on the source of inflammation and the type of infectious agent. Therefore, a person who has a history of this dysfunction, possible manifestations of necrotizing angina, pneumonia, lesions of the skin and so on.
• If the agranulocytosis develops thrombocytopenia, then the person begins to suffer increased bleeding tissue.
• First of all infectious lesions begin to touch the human oral cavity, because it contains a large amount of pathogenic microflora. With a low content of granulocytes in the blood, the patient, in the first place, starts various problems with the oral cavity, which are manifested 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 likely to enter the foci of infection. Therefore, the affected area is covered with fibro-necrotic tissue. On the surface of infection localization, a dirty-gray run can be detected, and bacteria begin to multiply 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 general blood flow are carried throughout the body of the patient, causing symptoms of general intoxication in a difficult stage. Therefore, the patient develops a fever in high form, accompanied by a temperature of about forty degrees and above. There is also weakness, nausea and headache.

Read more about the symptoms of agranulocytosis here.

Diagnosis of agranulocytosis

Diagnosis of agranulocytosis is the following:

• A general blood test, as well as urine and feces.
• A blood test, in which it is important to establish the level of reticulocytes and platelets.
• Taking a sternal puncture, as well as studying the myelogram.
• Obtaining data on the sterility of blood, which are taken repeatedly, at the peak of the manifestation of fever. It is important to study the sensitivity of pathogenic flora to antibiotic agents.
• Studies of biochemical blood analysis, in which it is possible to determine the amount of total protein and protein fractions, sialic acids, fibrin, seromucoid, transaminase, urea and creatine.
• Passage of examination at the otolaryngologist.
• Passage of examination at the dentist.
• X-ray examination of the lungs.

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

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

[10], [11], [12], [13], [14], [15], [16], [17], [18], [19]

Blood test for agranulocytosis

With agranulocytosis, an important blood test is an important laboratory test. The presence of this disease can be evidenced by such results as an increase in ESR, the presence of leukopenia and neutropenia, which can be characterized even by the complete disappearance of granulocytes. The amount of granulocytes is less than 1 × 10 ⁹ cells in μl of blood. Also for the clinical picture of the disease is the occurrence of some lymphocytosis. Sometimes anemia is established, that is, a reduced content of red blood cells. There may also be thrombocytopenia and / or monocytopenia. An important factor in establishing a diagnosis is the detection of plasma cells in the blood, about one or two percent.

Biochemical blood test (BAC) studies show that gamma globulins, sialic acids, fibrin and seromucoid are contained in an increased volume.

[20], [21], [22], [23], [24], [25], [26], [27], [28]

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:

• Elucidation of the cause of pathology and its elimination.
• Creation for the patient of optimal conditions for recovery, which include full sterility.
• Taking preventive measures against the occurrence of infectious infections, as well as therapy for existing infections and their complications.
• Passage of the procedure of transfusion of leukocyte mass.
• Purpose of steroid therapy.
• Passage of procedures that stimulate leukopoiesis.

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

• the cause of the disease and the nature of its origin,
• degree of disease progression,
• existing complications,
• sex of the patient,
• age of the patient,
• available in the history of the accompanying disease underlying disease.

In parallel with the treatment of the main problem, the following therapies are recommended:

• If there is such a need, then it is possible to prescribe detoxification therapy, which is carried out in a standard way.
• According to the patient, anemia is treated.
• With the symptoms present, the patient is treated with a hemorrhagic syndrome.
• Perhaps the corrective effect on other actualized problems.

Let us consider in more detail the methods of therapy of agranulocytosis available in practice:

• If the patient has a significant degree of leukopenia together with agranulocytosis, then this set of problems is an indication for the use of etiotropic treatment. Such therapy consists in the cancellation of sessions of radiotherapy and the use of cytostatics. Patients who received a sharp decrease in white blood cells due to taking drugs that do not have a direct myelotoxic effect, with medicinal agranulocytosis, should stop taking these medications. In this case, if the drugs have been canceled in a timely manner, there are great chances for a rapid recovery of the level of leukocytes in the blood.
• Acute agranulocytosis requires the patient to be placed 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. Visiting relatives of sick people is prohibited until the patient's blood state improves.
• In this state of the patient, the treatment staff conducts therapy and prophylaxis of infectious complications. Antibacterial drugs that do not have myelotoxic effect are used. Such therapy is indicated if the level of leukocytes in the blood is reduced to 1x10 ⁹ cells per one μl of blood and, of course, at lower values. There are also some nuances in correcting certain conditions: diabetes mellitus, chronic pyelonephritis and other foci of infectious processes need the use of antibiotics in the form of prophylaxis and at a higher level of white blood cells - about 1.5x10 ⁹ cells per 1 μl of blood.

When infectious therapy as a preventive measure, specialists use one or two antibacterial drugs that are given to the patient in an average dosage. Medications 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 wide spectrum of action. The doses are given at the maximum, the drugs are administered orally, as well as intravenously or intramuscularly.

To suppress the multiplication of pathogenic intestinal flora in most cases, the administration of nonabsorbable (which is not absorbed into the blood) antibiotics is prescribed.

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

Complex therapy presupposes a rather frequent prescription of preparations of immunoglobulin and antistaphylococcal plasma.

All of the above anti-infectious 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 by the body of the introduced mass. For this purpose, they use the system of HLA antigens, which allows to check the compatibility of the leukocytes of the patient with the leukocytes of the injected drug.
• Therapy with glucocorticoids. Indications for the use of this type of medication is immune agranulocytosis. The effectiveness of this treatment is due to the fact that glucocorticoids have a retarding effect on antileukocyte antibodies, more precisely, on their production. Also, the drugs of this group have the ability to stimulate leukopoiesis. According to the standard scheme, in this case Prednisolone is used, which is shown to be used from forty to one hundred milligrams a day. The dose gradually decreases after the blood indicators show the process of improving the patient's condition.
• Stimulation of leukopoiesis. Such a measure is required for myelotoxic and congenital agranulocytosis. Modern medical practice states the rather successful use of granulocyte colony-stimulating factor (G-CSF).

Prevention of agranulocytosis

Prevention of agranulocytosis can be expressed in the following actions:

• The use of procedures that make up the number of leukocytes in the blood. These procedures include granulocyte colony-stimulating factor (G-CSF) therapy or granulocyte-macrophage colony-stimulating factor (GM-CSF).
• It is important to include medicines in the prevention scheme of leukocyte loss, which stimulate their production and prevent the disappearance of these particles.
• It is necessary to establish a diet that includes a large number of products that contribute to 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 preferably juices and mixtures of juices from these natural riches. It is also important to include in the menu of the patient sea kale, avocado, peanuts and spinach.

Prognosis of agranulocytosis

The prognosis of agranulocytosis in adults with different types of disease is as follows:

• With acute agranulocytosis, the operative and correctness of medical care to a patient has a great degree. On this depends the possibility of recovery, as well as the prevention of infectious complications. An important point is the amount of granulocytes in the blood, determined after a laboratory test. No less important factor that influences a favorable prognosis is considered the initial state of human health before the emerged pathology.
• 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.

Prospects for recovery in childhood forms of the disease is as follows:

• The prognosis for Costman's syndrome (child genetic genetically determined agranulocytosis) has hitherto been unfavorable to the extreme. Especially, for newborns, the presence of the disease foreshadowed a lethal outcome. But recently the granulocyte colony-stimulating factor (G-CSF) has proved to be a good therapy.
• With agranulocytosis against a background of cyclic neutropenia in children, the prognosis is relatively favorable. As age changes soften the course of the disease.
• Agranulocytosis in newborns with isoimmunal conflict is itself within ten to twelve days of the birth of the baby. It is important to prevent the development of infectious complications, which is expressed in properly applied antibiotic therapy.

Agranulocytosis is a serious blood disease leading to no less serious complications of infectious nature. Therefore, for a favorable outcome in this pathology, it is important to start appropriate treatment in time, and also to follow all the recommendations of specialists.