Leukopenia is a decreased level of leukocytes in the total cellular composition of the blood to a border of less than 1.5 × 109 / L. In the event that there is an absolute absence of leukocytes in the blood, a condition called "agranulocytosis" develops. The incidence of leukopenia with a severe course of no more than 1 case per 100 000 population, and the incidence of congenital leukopenia is 1 per 300,000 people. The level of mortality from leukopenia of varying severity is within 4-40%.
In the structure of morbidity prevail leukopenia, provoked by the action of chemotherapeutic drugs used in cancer diseases.
In addition to chemotherapy, an adverse reaction in the form of leukopenia has a large number of drugs of various groups (antipsychotics, hormonal drugs), so the elderly half of the population suffer more from leukopenia. For women, the emergence of this pathology is more characteristic than for men.
Leukopenia is a polyietic syndrome, which can act both as a primary condition and as a complication of other diseases. Among the main reasons for the development of leukopenia should be noted:
- a congenital defect in the genetic sphere, transmitted through an autosomal recessive type, so congenital leukopenia can be attributed to a group of sporadic diseases;
- myelotoxic leukopenia is provoked by the action of chemotherapeutic drugs, used not only for oncohematological diseases, but also for systemic oncological process in the body;
- direct tumor lesion of the bone marrow, which is the central organ of hematopoiesis;
- a violation of metabolic processes in the body, accompanied by a lack of vitamins of group B, copper and folic acid;
- infectious disease of the body (cytomegalovirus infection, rubella virus, Epstein's virus - Barr, hepatitis , AIDS);
- different forms of tuberculosis ;
- medicines used as a therapy for diseases of various organs and systems (mercury diuretics, nonsteroidal anti-inflammatory drugs, antidepressants, antithyroid and antihistamines);
- rheumatoid arthritis and renal failure, for which the use of captopril and probenecid, often provoke signs of leukopenia;
- long-term work with chemicals (benzene, pesticides).
There are three main etiopathogenetic mechanisms of the occurrence of leukopenia: a violation of the production of leukocytes in the organs of hematopoiesis, a malfunction in the circulation of leukocytes or their redistribution, and the acceleration of the destruction of neutrophils.
Normally, leukocytes are localized in the bone marrow, transported with circulating blood to all vital organs and tissues. In the blood there are two types of leukocytes: freely circulating with blood flow and adhered to the wall of the vessel. On average, the duration of the leukocytes in peripheral blood is no more than 8 hours, after which they are redistributed into tissues. Excessive destruction of leukocytes can be provoked by the action of antileukocyte antibodies.
When chemotherapy and radiation exposure to the bone marrow, the first link is broken, that is, mature leukocytes are not formed because of the mass death of young proliferating cells of the bone marrow.
With infectious disease and bacterial sepsis, there is a sharp decrease in the freely circulating fraction due to increased adhesion of leukocytes to the vascular wall, provoked by the action of endotoxins. Any parasitic lesion of the body occurs with splenomegaly and excessive accumulation of leukocytes in the spleen, in connection with which, there is an insufficient level of leukocytes in the blood.
Congenital forms of leukemia, like leukemia or aplastic anemia, are characterized by a violation of the main stem cells of the bone marrow, from which the proliferation of leukocytes occurs.
For HIV infection and AIDS, a destructive effect on bone marrow stromal cells is characteristic, which entails a breakdown in the hematopoiesis system, as well as accelerated destruction of already existing mature leukocytes in the blood.
With long-term admission of certain groups of drugs, leukopenia is explained by toxic, immune and allergic effects on the body as a whole and on the central organs of hematopoies in particular.
As a rule, leukopenia does not manifest itself in any way, that is, there are no specific clinical symptoms indicative of a decrease in the level of leukocytes in the blood and not characteristic of other diseases.
A slight decrease in the level of white blood cells can not cause any complaints from the patient at all, and the symptoms of a health disorder are observed when infectious or bacterial complications are attached. In addition, the duration of leukopenia is of great importance. So, if leukopenia at 0, 1 × 109 / L is observed within seven days, then the risk of an infectious complication is no more than 25%, while the duration of the same leukopenia is 1.5 months in 100% of cases accompanied by bacterial or infectious complications of varying severity.
With respect to the risk of an infectious complication, an important factor is the rapidity and dynamics of the development of leukopenia. There is a definite dependence - the more rapidly the level of leukocytes circulating in the blood decreases, the higher the risk of an infectious complication in the patient, and on the contrary, people with slow leukopenia are less prone to complications.
The most important and often the most primary sign of the onset of an infectious disease against a background of leukopenia is an increase in body temperature. It should be noted that people who are on treatment with hormonal drugs, do not suffer from fever even when the infectious agent is attached. In 50% of cases, febrile patients with leukopenia can not reliably establish the cause and focus of the infection, since in most cases, the focus of infection is endogenous flora, which is inactive for a long time and forms colonization infectious foci.
The main focus of infection, which is actively populated by pathogenic microorganisms in leukopenia, is the oral cavity. In connection with this, along with fever, patients suffering from leukopenia often complain of the appearance of painful ulcers on the oral mucosa, bleeding gums, swallowing pain and hoarseness.
Separately, we should consider the clinical features of the course of leukopenia, as manifestations of the cytostatic disease that has arisen as a result of the effects of drugs that are used as a chemotherapy for oncological diseases. This disease is characterized by the defeat of all germs of hematopoies, in connection with which, there is a decrease in the level of red blood cells, leukocytes and platelets, manifested not only in fever, but hemorrhagic syndrome (bleeding and hemorrhage), anemic syndrome (weakness, pale skin), syndrome necrotic enteropathy (abdominal pain without clear localization, loosening of the stool, flatulence) and oral syndrome (necrotizing ulcerative stomatitis).
Unfortunately, cytostatic disease, one of the manifestations of which is leukopenia, is often complicated by the addition of not only infectious complications, but also bacterial septic damage to the body, often resulting in death. In bacterial septic lesions there is a rapid increase in clinical symptoms until signs of septic shock (acute cardiovascular and respiratory failure) appear.
If a patient has signs of leukopenia, the inflammatory process proceeds with some peculiarities. So, for example, the inflammatory process in soft tissues proceeds with insignificant local manifestations (insignificant pain and hyperemia of the skin), however the general intoxication syndrome is rather well expressed.
The peculiarity of bacterial pneumonia, which arose against the background of leukopenia, is the absence of X-ray signs with a pronounced intoxication syndrome.
In patients with leukopenia, a frequent complication is necrotizing enterocolitis, which is manifested by minor intestinal manifestations, but the rapid development of peritonitis and perianal inflammatory processes (paraproctitis).
Against the background of leukopenia, in 10% of cases, symptoms of myoclostridial necrosis occur - acute muscular pain, swelling and increase in the volume of soft tissues, the presence of intermuscular emphysema during radiography. Myoclostridial necrosis has a spontaneous rapid flow and is rapidly complicated by septic shock.
A frequent manifestation of the decrease in the number of leukocytes in the female body is leukopenia of the uterus, which is manifested by changes in the menstrual cycle in the form of an increase in the volume of menstrual flow, irregularity of menstruation, and uterine bleeding.
Degrees of leukopenia
To assess the severity of the disease, the patient has a generally accepted international gradation of leukopenia. According to the classification of leukopenia according to the severity of the flow, 3 degrees of severity are distinguished.
At the first degree of leukopenia, the level of leukocytes in the blood is observed up to 1.5 × 109 / L and at this stage there is a minimal risk of bacterial complications in the patient.
For grade II leukopenia, a decrease in circulating white blood cells in the blood to a level of 0.5-1.0 × 109 / L is characteristic. The risk of joining infectious complications is at least 50%.
III degree of leukopenia, which has the second name "agranulocytosis", is characterized by an acute shortage of leukocyte count in the blood to a border of less than 0.5 × 109 / L and is very often accompanied by infectious complications.
In addition to the division of leukopenia according to the severity of the course, there is a classification of this condition depending on the extent of manifestation of its signs. So, in duration, leukopenia is divided into acute (duration of laboratory changes does not exceed three months) and chronic (long-term course of the disease, exceeding three months).
Acute leukopenia should be considered as a transient state, observed in various viral diseases. Chronic leukopenia has more complex mechanisms of formation and is divided into three forms: autoimmune, congenital or idiopathic (the cause of leukopenia can not be determined), redistribution (blood transfusion and anaphylactic types of shock, in which there is accumulation of leukocytes in the tissues of the intestine, lungs and liver).
Leukopenia in children
For children, the criterion for establishing leukopenia is a decrease in the level of leukocytes less than 4.5 × 109 / L. As a rule, speaking about reducing the number of leukocytes in children, we mean a lowered level of neutrophils.
The most common cause of neutropenia in infants are infectious diseases, namely, mumps, measles , rubella, influenza and tuberculosis. The presence of leukopenia in the septic state is an unfavorable prognostic sign.
In childhood, leukopenia often acts as a side reaction to the administration of various drugs, which include: antibacterial drugs (Chloromycetin, Streptomycin), antihistamines, sulfonamides and organic compounds of arsenic.
During the newborn period, leukopenia is one of the components of such pathological conditions as megaloblastic anemia, pancytopenia and hypoplastic anemia of Fanconi. Children suffering from congenital gamma globulinemia are prone to the recurrence of granulocytopenia.
The peculiarity of leukopenia in children is the rapid development of clinical manifestations and rapid attachment of infectious complications. For children, sluggish forms of leukopenia are almost not characteristic, which greatly facilitates the early diagnosis of this pathological condition.
Due to the fact that isolated leukopenia is very rare in childhood, great attention should be given to diagnostic measures that help to establish the correct diagnosis. So, in addition to the standard count of leukocytes in a general blood test and examination of the leukocyte formula, children with severe leukopenia in combination with anemia and thrombocytopenia are shown to conduct additional research methods:
- a blood test for the presence of immature blast cells;
- puncture or trepanobiopsy of the bone marrow to determine the pathogenesis of the development of leukopenia (failure in the leukopoiesis system, acceleration of destruction of leukocytes in peripheral blood, and the presence of blast cells);
- a blood test for the presence of antinuclear antibodies, rheumatoid factor, anti-granulocyte antibodies;
- biochemical blood test with determination of hepatic samples, markers of viral hepatitis, level of B vitamins.
Separately, mention should be made of the transient form of neonatal leukopenia, which is a variant of the norm and does not need a medical correction.
Transient leukopenia occurs in the infant's thoracic period and is caused by the impact of maternal antibodies, which have been reported to the children's organism even in the prenatal period. In this condition, a persistent decrease in the level of granulocytes (within 15%) is observed in the infant, while the normal values of the total number of leukocytes are preserved. As a rule, this condition passes by itself when the child reaches the age of four.
There is a congenital hereditary form of leukopenia, which is a separate nosological unit - "Costman's disease". The first case of this disease was registered in 1956, and then the nature of its occurrence was clarified. It turned out that this is a hereditary family-type leukopenia, transmitted autosomal recessive type, and manifested as complete absence of neutrophilic granulocytes in the circulating blood. Children born with Costman's syndrome from birth are susceptible to serious complications in the form of infectious diseases, as they lack their own immunity ( furunculosis , periodontitis , abscessed pneumonia, absentee hepatitis). The main pathogenetically grounded drug used to treat children with Costman's syndrome is the colony-stimulating factor.
For effective treatment of a patient with a severe degree of leukopenia should be isolated in a separate room, which will only have access to medical personnel using all means of protection (gown, medical cap, shoe covers, gauze dressing and hand treatment with antiseptic drugs).
According to the recommendations of hematologists, patients with a mild form of leukopenia do not need specific treatment and all medical measures should be aimed at preventing possible infectious complications, as well as eliminating the root cause of this pathology.
Severe form of leukopenia requires an individual and versatile approach to treatment and includes such areas:
- etiopathogenetic treatment, that is, treatment of the underlying disease that provoked leukopenia;
- maintenance of bed rest in sterile conditions;
- correction of eating behavior;
- preventive measures to prevent possible infectious complications;
- hormone therapy;
- replacement transfusion of leukocyte mass (under condition of absence of antibodies to leukocyte antigens);
- stimulation of the leukopoiesis process.
A major role in the treatment of leukopenia is the etiologic orientation of therapy, that is, if there is autoimmune agranulocytosis or aplastic anemia, then it is advisable in this case the use of immunosuppressive therapy (Azathioprine at a daily dose of 1 mg per 1 kg of weight, 15 mg mg per day for at least 5 days , Cyclosporine in a daily dose of 10 mg per 1 kg of weight).
In a situation where leukopenia is a side effect of the use of any medication, you must immediately stop taking this medication. If leukopenia is combined with a deficiency of vitamin B12 or folic acid, you must prescribe folic acid with a calculation of a daily dose of 1 mg per 1 kg of weight, leucovorin by 15 mg intramuscularly.
Auxiliary drugs include drugs that improve metabolic processes in organs and tissues at the cellular level, thereby indirectly accelerating leukopoiesis: Pentoxyl 200 mg 3 r. per day, for 0.5 grams of 4 p. per day, Leucogen to 0.02 g 3 r. per day, Methyluracil 0.5 g 4 r. per day. These drugs promote the acceleration of cellular regeneration, and also improve the humoral and cellular immunity.
As a preventive measure to prevent infectious complications, patients with leukopenia are recommended to perform intestinal decontamination, since the digestive tract is the main source of infection in this situation. Antibacterial agents of the fluoroquinolones group should be used (Ciprofloxacin 500 mg 2 times daily), Sulfamethoxazole - Trimethoprim 960 mg 1 p. per day for 5-7 days.
Therapy of septic lesion is performed according to certain standards: mandatory catheterization of the radial or femoral artery and central vein. As a pathogenetic therapy for septic shock, it is advisable to use hormonal therapy in small doses (hydrocortisone 250 mg per day) to prevent possible complications in the form of hemorrhages in the adrenal glands, accompanied by adrenal insufficiency.
In a situation where leukopenia is accompanied by acute respiratory insufficiency, an early tracheostomy and transfer of the patient to mechanical ventilation are recommended.
If the patient's condition is not severe, then it is recommended to conduct an enteral type of nutrition with the correction of eating behavior, that is, a special sparing diet is prescribed. In severe forms of leukopenia, up to agranulocytosis, gastroparesis and erosive esophagitis are often observed, therefore, such patients receive the enteral method with the help of a nasogastric tube.
The group of pathogenetically important drugs include colony-stimulating factors, which can reduce both the depth and duration of leukopenia. With oncological diseases, colony-stimulating factors are used not only for treatment, but also as a preventive agent that prevents the development of chemotherapy leukopenia. The drugs of choice with proven efficacy are Filgrastim in a daily dose of 5 mg per kg of body weight intravenously once, Molgrastimin at a dose of 5 μg / kg per day subcutaneously, which are used before the normalization of white blood cell counts. These drugs are not recommended for use in the form of leukopenia.
With the existing complications of leukopenia, a method of transfusion of granulocyte concentrate is used in the patient in the form of development of generalized sepsis, for which the blood is taken from the donor and apheresis of granulocytes is made using automated blood fractionators. Obligatory point in this manipulation is the special preparation of the donor, which implies the administration of the Colony-stimulating factor to the donor at a dose of 5 mg / kg and Dexamethasone in a dose of 8 mg for 12 hours before blood sampling. This method of treatment is not widely used, since there are a large number of adverse reactions from its use - acute respiratory failure, alloimmunization, as well as the risk of contracting a viral infection.
There are many recipes for traditional medicine that should not be taken as the main remedy, but as a prevention of complications, and in addition to the basic methods of treatment, it is worth using.
The best means of alternative medicine, which is largely able to improve the processes of hemopoiesis and leukopoiesis is Mumiye. It should be borne in mind that the positive and lasting effect of Mumiye's use should be expected only after the course of the use of this remedy according to a certain scheme: the first ten days are taken Mumiye in a daily dose of 0.2 g, which should be divided into three doses, the next 10 days the daily dose should be 0.3 g and the last 10 days Mumiye is taken in a dose of 0.4 g.
When talking to a patient suffering from leukopenia, the doctor must warn the patient about the possible risk of complications and the severe consequences of protracted leukopenia that occurs when the patient fails to follow the recommendations on nutrition and medication. Such consequences include: the risk of provocation of cancer, infection with HIV infection, aleukia (complete disruption of the maturation of blood cells involved in cellular immunity).
A balanced diet with leukopenia can significantly improve the blood test, however, do not forget that this condition requires a qualified approach to correcting the daily diet. Principles of dietary nutrition are aimed at stimulating the process of proliferation, differentiation and maturation of blood cells.
There are a number of foods that can suppress hematopoiesis. These products include those that contain a large amount of cobalt, lead and aluminum (seafood, mushrooms, legumes).
You should give preference to products of vegetable, and not animal origin. The same applies to fats, i.e., it is necessary to exclude butter, smalets, lard from the ration, and replace them with high-quality olive, sunflower refined oil.
As the first dishes should be prepared soups, cooked on vegetable or fish broth. Do not limit the use of any vegetables, fruits and herbs in raw form and in large quantities, as they are rich in amino acids, trace elements and vitamins.
Food with leukopenia should be rich in protein, however, preference should be given to low-fat fish and meat, steamed and / or boiled, and soy products. An obligatory criterion for dietary nutrition in leukopenia is the sufficient intake of fermented milk products, since it is necessary to maintain a normal beneficial flora in the intestine, thereby preventing infectious complications.
The main criteria for correct balanced nutrition in leukopenia include: fractionality (five meals a day in small portions), caloric intake (daily calories should average 2500-3000 kcal) and continuity.
Patients who underwent chemotherapy treatment of oncological diseases, in addition to recommendations for correcting eating behavior, should undergo a recovery treatment using a decoction of flax seeds, which has a proven antitoxic effect. To prepare this broth, you need to insist on a water bath flax seeds in the calculation of 4 tablespoons. for 2 liters of boiling water. Take the broth is necessary for 1 hour before each meal for 1 month.