Neutropenia - is a reduced level of neutrophils in the total cellular composition of the blood to a level of less than 1,500 cells / mm.The severity of the patient's condition and the risk of severe complications and infection of bacterial origin depends on the severity of neutropenia.
For the selection of effective treatment is necessary not only to establish the fact of reduction of neutrophil cells in normal performance of other germs blood, but also reliably establish etiopathogenetic mechanism of occurrence of this dangerous for the patient's health status.
incidence of severe neutropenia is no more than one episode of 150 000 population.The mortality rate from varying degrees of severity of neutropenia is within 10-60%.
Severe neutropenia, in which the level of neutrophils in the peripheral blood is less than 500 cells / mm, are extremely rare, but the management of patients with agranulocytosis should be aware of extremely high risk of inflammatory nature, caused by a
In order to understand the pathogenetic mechanisms of neutropenia, it should be considered a normal physiological processes of blood formation and proliferation of these vital blood cells.The whole period of life of neutrophils takes 15 days and is divided into three phases: the proliferation of the main blood-forming organs, the free circulation in the peripheral blood flow, and, if necessary, in the organs and tissues and their physiological destruction.
Violation of each of these periods of life of neutrophilic granulocytes may be an agent provocateur for the development of some form of neutropenia.Thus, impaired proliferation and differentiation of granulocytes in the structure of the bone marrow can occur as a result of a congenital defect, and in various autoimmune diseases, oncological pathologies of different localizations.
Due to the fact that a larger percentage of neutrophils is not free in the blood stream circulation, and adhesive to the vascular wall (so-called neutrophilic granulocytes marginatnaya fraction), the conditions for development psevdoneytropenii.This condition is characterized by a decrease in neutrophils in the circulating blood, although the overall level of neutrophils remained unchanged due to the large number of adherent neutrophils.
Isolated destruction of a large number of neutrophils occurs only when exposed antileykotsitarnyh antibodies.
Neutropenia refers to the category polyetiology syndromes, so it can act as a primary condition, and is a complication of other diseases.Congenital diseases accompanied by neutropenia syndrome are cyclic neutropenia, immunnodefitsitnye congenital condition, a genetic agranulocytosis, storage diseases (acidemia, glycogen storage disease), mielokaheksiya phenotypic abnormalities (metaphyseal chondrodysplasia, congenital dyskeratosis).
to acquire diseases accompanied by neutropenia syndrome include: diseases of the autoimmune nature (benign anemia in children, systemic lupus erythematosus, granulomatosis Vegera), pathology of the bone marrow (aplastic anemia, metastasis localization in the medullary canal, prolonged exposure to the conditions of ionizing radiation)infectious nature of the disease (generalized bacterial sepsis, HIV and AIDS, cytomegalovirus defeat tuberculosis of different localization).
neutropenia separate group are so-called "formulations", which provoked the toxic effect of certain groups of medicines (mercury diuretics, nonsteroidal anti-inflammatory drugs, antidepressants, and antihistamines antitireodnye).
typical clinical symptoms in neutropenic syndrome develops in marked decrease in the index of neutrophils in the peripheral blood and manifests symptoms similar to aplastic anemia.
first characteristic symptom of neutropenia are necrotic and ulcerative changes with localization in the oral cavity (tonsillitis, stomatitis and gingivitis), thorax (pneumonia with a tendency to abscess and pleural empyema), the skin (subcutaneous abscesses, nail panaritiums and intermuscular phlegmon)adrectal soft tissue localization (in the pyogenic abscess fistula form).
In a situation where the necrotic and ulcerative processes affect the small intestine, develops clinical necrotic enteropathy, which manifests the appearance of acute abdominal pain without clear localization, nausea and vomiting not related to eating and intestinal atony with a tendency of the patient to constipation.Danger necrotic enteropathy is its tendency to develop complications that threaten the life of the patient (intestinal perforation and peritonitis).
If severe neutropenia, a provocateur which is long-term use of anticonvulsants, sulfonamides, giposensebiliziruyuschih and analgesic medicines, formed a vivid clinical syndrome with acute debut and high mortality.This form refers to an immune neutropenia, agranulocytosis, conditioned responses antileykotsitarnyh antibodies on their own neutrophilic granulocytes and manifests itself in acute arisen fever, headache, aching pain in the large joints, and severe weakness.In various organs and tissues appear ulceration with an inflammatory component (oral cavity, esophagus, vagina and intestines) until the development of generalized septicemia.The duration of the acute period of 3-4 days in 30% of cases are fatal.
Thus, each patient having frequent infections, especially occurring in severe form, should be suspected in the presence of neutropenia, especially in patients treated with radiation or cytostatic treatment.
When initial manifestations of neutropenia no typical complaints of the patient, and therefore, it is necessary to pay special attention to the objective examination of the patient with a mandatory inspection of the oral cavity, skin, anus, places and venipuncture catheterization central vessels, and abdominal palpation.
Besides typical clinical symptoms to establish a definite diagnosis "neutropenia" great importance is the identification of the laboratory changes.
Special attention should be given to laboratory examination of patients with febrile fever, which implies not only a general blood count with granulocytes, but if necessary, two blood cultures for the presence of pathogenic bacteria and fungal infections.In postoperative patients should be evaluated seeding content from the drain of the graduate and the presence of loose stools recommended to perform fecal clostridial infection.
great importance in the diagnosis of neutropenia is the study of hematopoietic function of bone marrow, in which it is possible not only to assess inhibition of a germ of blood, but also the cause of its occurrence.
Neutropenia in children
Neutropenia in children occurs as a manifestation of bone marrow hypofunction at different ages criteria neutropenic syndrome differ.Thus, neutropenia occurs in infants in the quantitative content of neutrophils in the blood of less than 1000 / l of peripheral blood.At older ages, the main sign of neutropenia is to reduce the quantitative content of neutrophils less than 1500 / mm.
At the age of one year often has neutropenia for acute or chronic (clinical picture develops within a few months).Primary neutropenic syndromes presented in three main forms: the immune neutropenia, chronic benign neutropenia and genetically determined form.
If neutropenic syndrome is weak, that is, the child has been a slight decrease in the number of neutrophils in the peripheral blood, most often noted asymptomatic disease.In some cases, there is often repeated episodes of acute respiratory viral diseases with a penchant for prolonged duration and adherence of bacterial complications.Typically, the data does not need neutropenia specific treatment and respond well to conventional therapy, antiviral and antibacterial drugs.
Children neutropenia moderate severity is characterized by a tendency to recurrent septic diseases, even before the emergence of signs of infectious-toxic shock.
Severe neutropenia in childhood is always accompanied by severe intoxication syndrome, hectic type of fever and severe suppurative complications destuktivnymi localized in the chest, mouth and abdomen.Subject to the wrong treatment given state quickly complicated by the development of signs of generalized sepsis, often ending in death.
When the diagnosis criteria are mandatory:
- determining whether family history of this disease;
- evaluation of clinical symptoms, available to the child, as well as a thorough examination of the primary objective;
- weekly evaluation hemogram mandatory counting all types of blood cells (in the case of cyclic neutropenia hemogram estimated at least twice a week for two months);
- moderate neutropenia in determining the appropriateness of the myelogram;
- when the virus-associated neutropenia must be a blood serum test for the growth antigranulotsitarnyh titer antibodies;
- in the presence of necrotic foci should produce a bacterial blood cultures to determine the specific flora, provoking neutropenic state.
in childhood can be observed not only secondary neutropenic status and primary hereditary neutropenia, each of which has its own peculiarities of and general symptoms.
general criteria specific to all hereditary neutropenia, are a fact of family history, the debut of the clinical and laboratory manifestations during the first months of life, genetic defects detected by molecular biological methods of diagnosis.
to severe forms of inherited neutropenia is Kostmana syndrome, which is characterized by autosomal recessive transmission of the defective gene, but can also be observed sporadic disease.When this pathology in the neonatal period the child has seen frequent episodes of bacterial and infectious diseases with a tendency to recurrent course.
syndrome Kostmana quantified marked decline in neutrophils in the blood up to the development of agranulocytosis (in 1 mm less than 300 neutrophils).Children with the syndrome Kostmana are at risk of acute myeloid leukemia incidence and mieloplasticheskim syndrome.The disease syndrome Kostmana is the rationale for the specific purpose lifelong therapy with colony-stimulating factors (filgrastim subcutaneously in a daily dose of 6 mg / kg body weight of the child).In case of failure of a sick child care colony recommended implementation of allogeneic bone marrow transplantation.
Another form of inherited neutropenia associated with impaired release of low activity of neutrophilic granulocytes of the medullary canal, so-called "mielokaheksiya."This type of neutropenia due to associated changes are manifested in accelerated apoptosis of granulocytes in the bone marrow and reduced chemotaxis.During the first year of life the child is observed relative neutropenia associated with marked eosinophilia and elevated levels of monocytes in peripheral blood.When you join a bacterial infection marked a pronounced leukocytosis, which quickly transformed into leukopenia.
a rare form of inherited neutropenic syndrome were observed in childhood, it is a cyclic neutropenia, which is inherited exclusively recessive.The principal difference of neutropenic syndrome from other forms of neutropenia is intermittent for the presence of crises."Cyclic" This is called neutropenia as a clear time frame debut next crisis (average 3-8 days), and a clear interictal period (2 weeks, 3 months).Since the onset of a crisis in the child appear bright clinical and laboratory signs of a sharp drop in the number of neutrophils and simultaneous monocytosis and eosinophilia, the emergence of foci of infection of various localization with purulent contents.After the end of neutropenic crisis in the child normalizing the overall health and performance of blood leukocyte.
principled approach to the treatment of cyclic neutropenia is the appointment of colony-stimulating factors for the two days prior to the anticipated onset of a crisis.Duration of a particular treatment depends on the speed normalization of granulocytes in peripheral blood.
Febrile neutropenia or "neutropenic fever" is an acute serious patient condition which occurs when the quantified reduction of neutrophils in the peripheral blood.
characteristic symptoms of febrile neutropenic syndrome is: febrile fever, chills expressed, alternated increased sweating, increased heart rate and a simultaneous sharp decline in arterial systolic pressure until the development of signs of hypotensive shock.
Due to the fact that in humans indicated marked decrease of neutrophils are responsible for the immune response and the formation of the inflammatory response in a patient is often unable to diagnose the primary site of the infection.And only in the long course of the disease, expressed in terms of immunosuppression, there is purulent-septic pockets of various localization.
Febrile neutropenia occurs most often in patients who are repeatedly exposed to massive cytostatic and radiation therapies that are used in malignant tumors, and is regarded as hyperergic reaction in response to the toxic effects of drugs.
Patients with febrile neutropenia, there is a severe course of infections that a healthy person does not cause long-term health problems.Due to the sharp immunosuppression, patients febrile neutropenia observed the rapid spread of infection from the primary tumor into all tissues and organs, thereby causing generalized sepsis.
main pathogens of infection in febrile neutropenia are anaerobic bacteria, Clostridium and pathogenic gram-positive cocci, and reinfection by herpes viruses and cytomegalovirus.
After determining reduction of neutrophils combined with a pronounced intoxication syndrome is mandatory blood sampling and biological fluids to determine the sensitivity to antibiotics of different groups for the purpose of selection of adequate and appropriate treatment regimen.
in antibacterial treatment of febrile neutropenia should follow the combined treatment regimens, based on the combined use of antibacterial agents that affect both the positive and gram-negative flora (Augmentin 375 mg 2 times a day orally, Medakson 1 g 1 p / day. Intramuscularly,Gentamicin at a daily dose of 2.4 mg / kg i.v.).