Agranulocytosis is a clinical and hematological syndrome, which is based on a sharp decrease or absence of neutrophil granulocytes among the cellular elements of peripheral blood. The disease is accompanied by the development of infectious processes, sore throat, ulcerative stomatitis, pneumonia, hemorrhagic manifestations. Of the complications, sepsis, hepatitis, mediastinitis, peritonitis are frequent. Of paramount importance for diagnosis is the study of the hemogram, bone marrow punctate, detection of anti-neutrophil antibodies. Treatment is aimed at eliminating the causes that caused agranulocytosis, preventing complications and restoring hematopoiesis.
Agranulocytosis is a change in the picture of peripheral blood that develops in a number of independent diseases and is characterized by a decrease in the number or disappearance of granulocytes. In hematology, agranulocytosis refers to a decrease in the number of granulocytes in the blood less than 0.75 x 109/l or the total number of leukocytes below 1 x 109/L. The congenital form is extremely rare; the acquired condition is diagnosed with a frequency of 1 case per 1200 people. Women suffer from agranulocytosis 2-3 times more often than men; usually the syndrome is detected at the age of over 40 years. Currently, due to the widespread use of cytotoxic therapy in medical practice, as well as the emergence of a large number of new pharmacological agents, the frequency of cases has increased significantly.
Causes of agranulocytosis
Myelotoxic agranulocytosis occurs due to the suppression of the production of myelopoiesis progenitor cells in the bone marrow. At the same time, there is a decrease in the level of lymphocytes, reticulocytes, and platelets in the blood. This type of agranulocytosis can develop when the body is exposed to ionizing radiation, cytostatic drugs and other pharmacological agents (levomycetin, streptomycin, gentamicin, penicillin, colchicine, aminazine), etc.
Immune agranulocytosis is associated with the formation of antibodies in the body, the action of which is directed against its own leukocytes. The occurrence of hapten immune agranulocytosis provokes the intake of sulfonamides, NSAIDs-pyrazolone derivatives (amidopyrine, analgin, aspirin, butadione), drugs for the treatment of tuberculosis, diabetes mellitus, helminthiasis, which act as haptens. They are able to form complex compounds with blood proteins or white blood cell membranes, becoming antigens, in relation to which the body begins to produce antibodies. The latter are fixed on the surface of white blood cells, causing their death.
Autoimmune agranulocytosis is based on a pathological reaction of the immune system, accompanied by the formation of anti-neutrophil antibodies. This type of agranulocytosis occurs in autoimmune thyroiditis, rheumatoid arthritis, systemic lupus erythematosus and other collagenoses.
Agranulocytosis, which develops in some infectious diseases (influenza, infectious mononucleosis, malaria, yellow fever, typhoid fever, viral hepatitis, polio, etc.) also has an immune character. Severe neutropenia can signal chronic lymphocytic leukemia, aplastic anemia, Felty syndrome, and also occur in parallel with thrombocytopenia or hemolytic anemia. Congenital agranulocytosis is a consequence of genetic disorders.
Pathological reactions accompanying the course of agranulocytosis, in most cases, are represented by ulcerative-necrotic changes in the skin, mucous membrane of the oral cavity and pharynx, less often – conjunctival cavity, larynx, stomach. Necrotic ulcers can occur in the intestinal mucosa, causing perforation of the intestinal wall, the development of intestinal bleeding; in the wall of the bladder and vagina. Microscopy of necrosis sites reveals the absence of neutrophil granulocytes.
Granulocytes are called leukocytes, in the cytoplasm of which a specific granularity (granules) is determined during staining. Granulocytes are produced in the bone marrow, therefore they belong to the cells of the myeloid series. They make up the largest group of leukocytes. Depending on the peculiarities of granule staining, these cells are divided into neutrophils, eosinophils and basophils – they differ in their functions in the body.
Neutrophil granulocytes account for up to 50-75% of all white blood cells. Among them, there are mature segmentonuclear (normally 45-70%) and immature rod-shaped neutrophils (normally 1-6%). The condition characterized by an increase in the neutrophil content is called neutrophilia; in the case of a decrease in the number of neutrophils, neutropenia (granulocytopenia) is spoken of, and in the absence of agranulocytosis.
In the body, neutrophil granulocytes act as the main protective factor against infections (mainly microbial and fungal). When an infectious agent is introduced, neutrophils migrate through the capillary wall and rush into the tissues to the focus of infection, phagocytize and destroy bacteria with their enzymes, actively forming a local inflammatory response. With agranulocytosis, the body’s reaction to the introduction of an infectious pathogen turns out to be ineffective, which may be accompanied by the development of fatal septic complications.
First of all, agranulocytoses are divided into congenital and acquired. The latter may be an independent pathological condition or one of the manifestations of another syndrome. According to the leading pathogenetic factor, myelotoxic, immune haptenic and autoimmune agranulocytosis are distinguished. There is also an idiopathic (genoine) form with an unidentified etiology.
According to the peculiarities of the clinical course, acute and recurrent (chronic) agranulocytoses are differentiated. The severity of the course depends on the number of granulocytes in the blood and can be mild (at a granulocyte level of 1.0-0.5 x 109 / l), moderate (at a level less than 0.5 x 109 / l) or severe (with a complete absence of granulocytes in the blood).
Symptoms of agranulocytosis
The clinic of immune agranulocytosis usually develops acutely, unlike myelotoxic and autoimmune variants, in which pathological symptoms occur and progress gradually. The early manifest manifestations of agranulocytosis include fever (39-40 ° C), severe weakness, pallor, sweating, arthralgia. Ulcerative-necrotic processes of the mucous membrane of the mouth and pharynx (gingivitis, stomatitis, pharyngitis, sore throats), necrotization of the uvula, soft and hard palate are characteristic. These changes are accompanied by salivation, sore throat, dysphagia, spasm of the chewing muscles. There is regional lymphadenitis, moderate enlargement of the liver and spleen.
For myelotoxic agranulocytosis, the occurrence of a moderately pronounced hemorrhagic syndrome is typical, manifested by bleeding gums, nosebleeds, bruising and hematomas, hematuria. When the intestine is affected, necrotic enteropathy develops, the manifestations of which are cramping abdominal pain, diarrhea, bloating. In severe form, complications in the form of intestinal perforation, peritonitis are possible.
With agranulocytosis, hemorrhagic pneumonia may occur in patients, complicated by abscesses and gangrene of the lung. At the same time, physical and radiological data are extremely scarce. Among the most frequent complications, perforation of the soft palate, sepsis, mediastinitis, acute hepatitis are possible.
The group of potential risk for the development of agranulocytosis consists of patients who have suffered a severe infectious disease, receiving radiation, cytotoxic or other drug therapy, suffering from collagenoses. From the clinical data, the diagnostic value is a combination of hyperthermia, ulcerative-necrotic lesions of visible mucous membranes and hemorrhagic manifestations. The following laboratory tests are prescribed:
- Blood test. The picture of peripheral blood is characterized by leukopenia (1-2 x 109 / l), granulocytopenia (less than 0.75 x 109/ L) or agranulocytosis, moderate anemia, with severe degrees – thrombocytopenia.
- Myelogram. The study of the myelogram reveals a decrease in the number of myelocaryocytes, a decrease in the number and a violation of the maturation of neutrophil germ cells, the presence of a large number of plasma cells and megakaryocytes.
- Antibody analysis. To confirm the autoimmune nature, anti-neutrophil antibodies are determined.
All patients with agranulocytosis are indicated for lung radiography, repeated blood tests for sterility, a study of biochemical blood analysis, a consultation with a dentist and an otolaryngologist. It is necessary to differentiate agranulocytosis from acute leukemia, hypoplastic anemia. It is also necessary to exclude HIV status.
Treatment of agranulocytosis
Patients with verified agranulocytosis should be hospitalized in the hematology department. Patients are placed in an isolation ward with aseptic conditions, where regular quartz treatment is carried out, visits are limited, medical personnel work only in caps, masks and shoe covers. These measures are aimed at preventing infectious complications.
In the case of necrotic enteropathy, the patient is transferred to parenteral nutrition. Patients need careful oral care (frequent mouthwashes with antiseptic solutions, lubrication of mucous membranes). Therapy begins with the elimination of the etiological factor (withdrawal of myelotoxic drugs and chemicals, etc.).
For the prevention of purulent infection, nonabsorbable antibiotics and antifungal drugs are prescribed. Intravenous administration of immunoglobulin and antistaphylococcal plasma, transfusion of leukocyte mass, and platelet mass in hemorrhagic syndrome is indicated. With an immune and autoimmune nature, glucorticoids are prescribed in high doses. In the presence of CEC and antibodies in the blood, plasmapheresis is performed. In complex treatment, leukopoiesis stimulants are used.
Prognosis and prevention
An unfavorable prognosis is observed with the development of severe septic complications, repeated development of hapten agranulocytosis. Prevention of agranulocytosis mainly consists in conducting thorough hematological control during the course of treatment with myelotoxic drugs, excluding repeated administration of medications that previously caused the patient to have immune agranulocytosis.