Agranulocytoses — the state which is characterized by considerable decrease in quantity of granulocytes, generally neutrophils or their total absence in peripheral blood. There is a look that the term "agranulocytoses" should be used at the level of granulocytes lower than 0,75*109/l and total quantity of leukocytes less than 1*109/l.
Epidemiology The acquired agranulocytoses meet at women more often 40 years are more senior, their frequency varies over a wide range, according to many authors the population are diagnosed for one patient for 1200. Inborn agranulocytoses are diagnosed very seldom.
Etiology and pathogeny Etiological factors in development of an agranulocytosis are medicines; streptomycin, gentamycin, penicillin, is more often levomycetinum (chloramphenicol), pyramidon, analginum, anti-thyroid, anticonvulsants, Butadionum, PASK, Pipolphenum, levamisole, himiopreparata of cytostatic action, beam agents, chemicals (gasoline, benzene, toluene, xylitol, alcohol), some infections (malaria, a typhoid, an infectious mononucleosis), viruses (hepatitis, flu), etc. At an unspecified role of a certain etiological factor speak about an idiopathic agranulocytosis.
The pathogeny of myelotoxic agranulocytoses consists in the termination of products of neutrophils owing to the cytolytic, anti-metabolic, allergic action inherent in an etiological factor. The immune agranulocytosis can be autoimmune (at a system lupus erythematosus, a pseudorheumatism, a chronic lymphoid leukosis, etc.) or connected with antibody formation to exogenous antigens — to haptens.
Classification Allocate the acquired and inborn forms of a granulocytopenia (neutropenia). The first can meet in the form of an independent disease or to be one of the syndromes accompanying the course of various pathological processes. On a clinical current differentiate acute and chronic neutropenias, on a pathogeny — myelotoxic and immune. Distinguish also agranulocytoses in which emergence a certain etiological factor and idiopathic forms with an unspecified etiology matter.
Approximate formulation of the diagnosis: 1. The agranulocytosis which developed against use of levomycetinum, proceeding with a deep granulocytopenia, complicated by bronchial pneumonia. 2. An idiopathic form of an agranulocytosis with the expressed quinsy, fever. 3. An agranulocytosis of immune genesis with fever, insignificant increase in a spleen.
Clinic Main kliniko-hematologic signs of acute agranulocytoses: the expressed intoxication against quinsy, aphthous stomatitis, ulcer and necrotic defeat of palatal handles, a uvula, a hard palate, gums, sometimes a digestive tract, lungs, a liver, generative organs; quite often note increase in regional lymph nodes (cervical, submaxillary, etc.) ; deep ulcerations of fabrics can be followed by plentiful bleedings from the destroyed vessels; at a necrotic enteropathy development of perforation of a gut and peritonitis is possible; pneumonia differs in scanty physical and radiological data; quite often meet an abnormal liver function and kidneys. Defeat of a granulocytopoiesis is, as a rule, characterized by an absolute neutropenia and decrease in absolute quantity of leukocytes; in a gemogramma can meet single blast and plasmocytes, the quantity of eosinophils is increased; in a miyelogramma promyelocytes and myelocytes usually prevail, the number of mature neutrophils is lowered up to total absence, the relative lymphocytosis and a plasmacytosis are found; also changes eritro-and a thrombocytopoiesis are quite often observed.
Chronic neutropenias represent a separate nosological form or a syndrome at various diseases. Among them allocate an idiopathic form with lack of instructions for influence of any etiological factor and demanding treatment only at the diagnosed infections. The immune form on the pathogeny does not differ from the mechanism of development acute immune neutropenias.
Inborn neutropenias on the pathogeny and a kliniko-hematologic picture represent heterogeneous group of diseases. We bring some of them.
The infantile genetic agranulocytosis (Kostman's illness) is inherited on autosomal recessively type. Characteristic signs are the heavy infections leading to death of patients in 5 — 10 months after the birth, an absolute deep neutropenia in a miyelogramma promyelocytes prevail, more mature granulocytes are practically absent. The mechanism of development of a granulocytopenia is caused by defect of haematopoietic stem cells.
The hereditary neutropenia — a disease of autosomal and dominant type, differs in a high-quality current. Tendency to infections is shown from first months of life and with age abates. The pathogeny of development of a neutropenia at various options of a disease is not unambiguous (disturbance of maturing of neutrophils in marrow, braking of receipt them in peripheral blood, immune and regulatory frustration, etc.).
The cyclic neutropenia is also inherited on autosomal dominantly type, usually shown in the early childhood or youth. As a rule, within 3 — 5 days the expressed neutropenia, fever, infections are observed, then on average by 21st day patients practically recover. The forecast is rather favorable, with age the clinical symptomatology abates. The ingibition of proliferation of stem cells mature neutrophils of marrow is the cornerstone of a pathogeny, also defect at the level of haematopoietic stem cells is not excluded.
Verification of the diagnosis Diagnosis is based mainly on a characteristic picture of a depression of a granulocytopoiesis according to researches of a gemogramma, miyelogramma and bioptat of marrow, ulcer and necrotic defeats of multiple localization, disturbance of a functional condition of kidneys and a liver are characteristic.
Treatment In all cases of treatment of agranulocytoses by the patient it is recommended to eliminate the factor which was the reason of their development. The system of treatment of autoimmune forms of a disease applies corticosteroid hormones in doses of 120 — 200 mg/days.
Patients are placed in aseptic conditions. By it appoint nonabsorbed antibiotics. Complex massive antibacterial therapy is appointed taking into account sensitivity of the allocated microflora.
At an immune agranulocytosis use corticosteroid hormones, immunodepressants, a plasma exchange (in the presence of the circulating antibodies or cell-bound immune complexes), sometimes a splenectomy. At chronic neutropenias along with treatment of a basic disease carry out a plasma exchange.