Aplastic anemia is a hereditary or acquired pathology of blood, caused by the damage to the stem cells of the bone marrow, which leads to the deep depression of hemopoiesis. The first information about aplastic anemia was received back in 1888, however as an independent nosological unit, aplastic anemia was registered only in 1904.
Hypoplastic anemia refers to the most severe form of hemopoiesis, since the lethality with aplastic anemia reaches a threshold of 80%.
One should not confuse aplastic anemia, which is a separate nosological form with a hypoplastic syndrome, which is only one of numerous manifestations of various diseases accompanied by impaired hematopoiesis of the bone marrow.
Fortunately, the incidence of cases of aplastic anemia does not exceed 5 episodes per 1,000,000 population, but the danger of this pathology is that it affects mainly children and young people. Sexual affiliation has no influence on the course and outcome of the disease.
Aplastic anemia causes
This pathology belongs to the category of polyethiologic diseases, that is, there are many reasons, one of which can take the dominant position and provoke a disorder in the hematopoiesis system of a particular patient. In addition, the so-called risk factors are distinguished, that is predisposing factors, the combination of which can not only contribute to the development of the disease, but also aggravate the course of the pathological process. Fortunately, in most cases it is possible to recognize the etiologic factor, which became the primary cause of the development of signs of anemia, but there are situations when it is not possible to determine the etiopathogenetic factor and in this case a diagnosis of idiopathic aplastic anemia is established.
Often, aplastic anemia acts as a side reaction from the use of certain groups of drugs, and the emergence of it does not depend on the dose or duration of the drug. To medicines that can provoke violations of all germs of blood in the bone marrow are: antihistamines, sulfonamides, tetracycline antibiotics, and also gold preparations. Especially often, aplastic anemia occurs in people taking levomycitin.
Separately, mention should be made of the role of ionizing radiation, which is used in X-ray methods of investigation, in the appearance of signs of aplastic anemia. This pathology is found among people working in X-ray rooms and in patients undergoing radio wave therapy.
Among hematologists, it is believed that during pregnancy, the risk of aplastic disorders in the bone marrow increases, but a pathogenetic explanation for this process has not yet been found. It should be noted that the detection of signs of aplastic anemia is an absolute indication for abortion, and cases of the transition of the disease to the stage of remission after an artificial delivery are recorded.
Another reason for the occurrence of aplastic anemia is the toxic effect on the body of drugs used as chemotherapy for the treatment of oncopathology, as well as prolonged exposure to pesticide and insecticide exposure.
Among the causes of disturbance of the hematopoietic function of the bone marrow, autoimmune diseases should be considered, in which immune mechanisms are directed at destroying not only pathogenic agents, but also the damage to own cells of bone tissue.
Aplastic anemia symptoms
Aplastic anemia is characterized by a slow-progressing course with a tendency to transition to a chronic form with periods of exacerbations.
All the clinical symptoms observed with aplastic anemia can be attributed to one of the three main syndromes: anemic, hemorrhagic or symptomatic complex of infectious complications. The appearance of signs of a syndrome is a consequence of the oppression of one or more germs of hematopoiesis.
The main complaints of patients with the development of signs of anemic syndrome caused by insufficient hemoglobin and red blood cells in peripheral blood are: severe weakness and decreased ability to work, dizziness and noise in the ears with hearing safety, a sense of lack of air and attacks of increased heart rate.
The first signs of hemorrhagic syndrome in a patient with aplastic anemia is the appearance of bruising and bruising on the skin of non-traumatic origin. Patients with aplastic anemia often complain of nasal bleeding, as well as bleeding gums. With severe inhibition of thrombocyte germ of hematopoies, a cerebral hemorrhage can occur.
Symptoms of a decrease in the level of leukocytes, as one of the pathogenetic links of aplastic anemia, is a predisposition to infectious diseases. Such patients belong to the category of "often ill", that is, during the year they have more than ten episodes of infectious diseases. The pronounced suppression of leukocyte production provokes purulent-septic complications (ulcerative necrotic tonsillitis , aphthous stomatitis , otitis, panaritium , postinfectious abscesses, generalized sepsis).
Even with a primary examination of the patient, one can determine the characteristic symptoms of aplastic anemia: marked pallor and cyanosis of the skin with the presence of bruises that do not have clear boundaries, and sometimes petty petechial rash. The increase in the boundaries of the liver and the appearance of edema of the lower limbs indicate the development of signs of heart failure . Auscultatory noted tendency to hypotension, sinus tachycardia and severe systolic murmur in all auscultative points. An important diagnostic sign of aplastic anemia is the unchanged spleen.
The degree of manifestation of a particular symptom complex directly depends on the degree of oppression of germs of hematopoiesis. Aplastic anemia of severe form has such diagnostic criteria: the level of neutrophils is less than 0.5 × 109 / L, platelets less than 20 × 109 / L, a corrected increase in reticulocytes of less than 1%. If the patient has at least one of these criteria in combination with a marked decrease in bone marrow cellularity, this is the reason for establishing the patient's diagnosis of "severe anemia of hypoplastic anemia".
Aplastic anemia in children
In childhood, congenital types of aplastic anemia, which include the anemia of Fanconi and Blackfen-Diamond, are more likely to debut.
Fanconi anemia is a hereditary pathology inherited by the autosomal recessive type, that is, cases of the disease are observed only in families where both parents are carriers of the pathological gene. Fanconi anemia is manifested not only in the deep depression of all types of hematopoiesis, but also in the appearance of developmental anomalies.
The debut of the disease falls on the age of 4-12 years, but hematological problems can arise immediately after the birth of the child. Congenital anomalies include: discrepancy of bone age in the passport, congenital malformations of the cardiovascular system , microcephaly , anomalies in the development of bone tissue, organs of the genitourinary system, lagging behind in psychomotor development. Hematologic changes occur at a later age (an average of 9 years) and symptoms of the hemorrhagic symptom complex prevail in the clinical picture, after which the signs of leukocytopenia and erythrocytopenia progressively increase.
This pathology has a rapidly progressing course, so in the absence of adequate treatment, the lethal outcome occurs within 6 months. The cause of death is most often massive gastrointestinal bleeding or cerebral hemorrhage. Complications of Fanconi anemia is the transformation of the disease into acute leukemia , as well as oncopathology of the gastrointestinal tract. The only effective method of treating Fanconi's congenital anemia is bone marrow transplantation.
The Blackfen-Diamond anemia belongs to the group of sporadic hereditary pathologies of the blood and is characterized by the defeat of the exclusively erythrocyte germ of the hematopoiesis. The debut of the disease is observed during the first year of life of the child.
Children with Blackfang-Diamond anemia have a typical phenotype: pale skin, large upper lip, wide-set eyes, dry split hair, lagging behind the age of the passport.
A characteristic change in the laboratory parameters of peripheral blood is progressive normochromic anemia with complete preservation of the proliferation of platelet and granulocyte cells.
This pathology is characterized by a sluggish chronic course with a tendency to spontaneous remission. The preferred method of treatment is the use of corticosteroid therapy, as well as the vital signs of transfusion of erythrocyte mass.
In childhood, acquired forms of aplastic anemia are extremely rare and manifest the same symptoms as in adults with complete absence of congenital pathologies.
If the child has signs of a violation of the hematopoietic function of the bone marrow, it is necessary to carry out differential diagnostics with such diseases as acute lymphoblastic and myeloblastic leukemia, megaloblastic anemia, hypersplenism syndrome, metastatic bone marrow injury.
A child with suspected congenital aplastic anemia is necessarily subject to a comprehensive examination, which includes: cytogenetic analysis after trepanobiopsy, a blood test for the presence of antibodies to blood cells, radiography with the definition of bone age, myelogram. All nearest relatives of a sick child are also subject to examination.
Aplastic anemia treatment
The key to the speedy recovery of patients with aplastic anemia is the early diagnosis of this pathological condition, an adequate assessment of the severity of the patient's condition, as well as an individual approach to choosing the appropriate treatment method in each case.
For the first time diagnosed aplastic anemia is a reason for hospitalization of a patient in a hospital, regardless of the severity of clinical manifestations and laboratory indicators.
In a situation where the etiopathogenetic factor is known to provoke the development of aplastic anemia, treatment should begin with the elimination of the underlying cause, in order to avoid further progression of oppression of hematopoiesis.
As therapeutic measures for diagnosed aplastic anemia, hematologists around the world use the following techniques: replacement transfusion of whole blood or its elements, bone marrow transplantation, and the use of drugs aimed at stimulating the processes of hematopoiesis.
Substitution therapy for aplastic anemia involves the use of a replacement transfusion of suitable donor blood or its individual elements (platelet, erythrocyte mass and granulocytes). This method of treatment is preventive, since blood transfusion only replenishes the stock of necessary elements of blood, but does not restore the function of hemopoiesis in the bone marrow. In addition, with this form of aplastic anemia, as an autoimmune, this method is not used, since the introduction of foreign cells the body begins to develop an immune response, which causes ineffectiveness of treatment.
It should be borne in mind that multiple infusions of donor blood are accompanied by excessive accumulation of iron in the body, which is deposited in vital organs, disrupting their structure. In this case, it is advisable to combine blood transfusion with the intake of drugs that promote the excretion of iron from the body. To avoid the process of rejection of the transplant before the procedure of bone marrow transplantation, it is inappropriate for the patient to use blood transfusion.
The most effective and at the same time the most dangerous method of treating aplastic anemia is bone marrow transplantation, since only this method can become a trigger mechanism for the normalization of the function of the hemopoiesis of the bone marrow. This method is used preferably at a young age of the patient after careful selection of a suitable donor, which may become the closest relative of the patient. Preparatory procedures for the transplantation of bone marrow stem cells are the impact on the patient's body of high doses of radiation exposure, as well as the use of chemotherapy drugs. The preparatory stage on the part of the donor is the collection of blood, the filtration of healthy stem cells from it and inserting them into the patient's bloodstream, through which they enter the bone marrow cavities, where the proliferation of healthy blood cells occurs.
To avoid complications, the patient is prescribed drugs to prevent graft rejection, but this fatal situation for the patient can not always be avoided. This method of treatment is expensive and requires compliance with certain conditions that are available only in specialized clinics, and therefore not widely used as aplastic anemia therapy.
Patients with aplastic anemia of autoimmune genesis need the use of immunosuppressive drugs, whose action is aimed at suppressing the inadequate functioning of the immune system. Drugs of choice in this situation are: Cyclosporine (daily dose is 10 mg / kg orally), Antitimocytic globulin (daily dose of 15 mg / kg intravenously) and Antilymphocytic globulin (daily dose of 130 mg intravenously drip). The use of immunosuppressants in most cases is accompanied by pronounced adverse reactions that threaten the patient's life ( anaphylactic shock , serum sickness, infectious diseases), for the prevention of which it is advisable to use corticosteroids (Prednisolone in a daily dose of 1 mg / kg). Undoubtedly, immunosuppressive therapy is one of the most effective methods of treatment of aplastic anemia, but there are cases when after taking medications of this group there is a relapse of the disease.
As an additional therapy, preparations stimulating the hematopoietic function of the bone marrow, the so-called colony-stimulating factors (Molgrimostin, Filgrastim, Leikomax) are applied to the main direction in the treatment of aplastic anemia. Preparations of this group are effective in stimulating the proliferation of granulocyte cells, so the area of their application are cases of aplastic anemia, accompanied by severe leukocytopenia. The course of therapy with colony-stimulating factors is at least two weeks and the preferred method of administering the drugs is parenteral at a daily dose of 5 mg / kg. The limiting factor in the application of the funds of this group is their high cost.
It has been scientifically proven that the androgen stimulating effect on all germs of hematopoiesis, in connection with which, androgen therapy in the treatment of aplastic anemia is now widely used. These drugs should be used only in case of incidence among men, and long-term courses of administration of drugs are recommended (Testosterone propionate twice a day for 1 ml of 5% solution or prolonged drug Sustanon 250 ml 1 time per month).
As a palliative method of treatment, radical splenectomy is used, which in 85% of cases has a positive effect in the treatment of aplastic anemia. The pathogenetic validity of this method is that when the spleen is removed, the sequestration of blood cells ceases and the production of antibodies against its own healthy bone marrow cells is sharply limited. This method of treatment is shown to all patients without signs of infectious complications.
Aplastic anemia prognosis
The prognosis for life, ability to work and the state of health of patients with signs of aplastic anemia directly depends on the severity of the disease and the depth of decline in the level of vital cells of hematopoiesis.
Unfortunately, to this day, the world statistics show disappointing data regarding the death rate from aplastic anemia, no matter how progressively the pharmaceutical industry develops with regard to the treatment of blood diseases. High mortality is observed among patients with severe pancytopenia and, to a greater extent, the cause of death is the generalized form of sepsis, as the final stage of leukocytopenia.
Significantly improved forecasts after the beginning of the application of radical methods of treatment (bone marrow stem cell transplantation, use of immunosuppressants). In 50-90% of cases, the use of these methods of treatment can achieve complete recovery of the patient.
The use of antitimocytic and antilymphocytic immunoglobulins in combination with Cyclosporine therapy allows only 60-70% of cases to achieve remission of the disease.