Aplastic anemia – it is a hereditary or acquired blood pathology caused by a lesion of the stem cells of the bone marrow, as a result of which a deep inhibition of hematopoiesis develops. The first information about aplastic anemia was obtained in 1888, but as an independent nosological unit, aplastic anemia was registered only in 1904.
Hypoplastic anemia refers to the most severe form of blood disorders, since mortality in aplastic anemia reaches a threshold of 80%.
Do not confuse aplastic anemia, which is a separate nosological form with the hypoplastic syndrome, which is just one of the many manifestations of various diseases involving impaired blood formation in the bone marrow.
Fortunately, the frequency of occurrences 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. Gender has no effect on the course and outcome of the disease.
Aplastic anemia causes
This pathology belongs to the category of polyetiological diseases, that is, there are many reasons, one of which may take a dominant position and provoke a violation in the hematopoietic system in one or another patient. In addition, there are so-called risk factors, 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 etiological 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 the diagnosis is made of idiopathic aplastic anemia.
Often, aplastic anemia acts as an adverse reaction from the use of certain groups of drugs, and its occurrence does not depend either on the dose or on the duration of this drug. Medicines that can provoke violations of all hemopoietic sprouts in the bone marrow include: antihistamines, sulfonamides, tetracycline antibiotics, and gold medications. Especially often aplastic anemia occurs in individuals taking Levometsitin.
Separately, mention should be made of the role of ionizing radiation, which is used in radiological research methods, in the appearance of signs of aplastic anemia. This pathology is found among people working in radiological rooms and in patients undergoing radio wave therapy.
In addition, diseases of viral etiology in the acute period (viral hepatitis, cytomegalovirus and herpes infection, HIV) can become provocateurs of aplastic anemia.
Among hematologists, there is an opinion that during pregnancy the risk of aplastic disorders in the bone marrow increases, however, a pathogenetic explanation of this process has not yet been found. It should be noted that the identification of signs of aplastic anemia is an absolute indication for abortion, and cases of transition of the disease to the stage of remission after artificial delivery have been reported.
Another cause 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 exposure to vapors of pesticides and insecticides.
Among the causes of impaired hematopoietic function of the bone marrow should be considered autoimmune diseases, in which the immune mechanisms are aimed at destroying not only disease-causing agents, but also damage to their own bone tissue cells.
Aplastic anemia symptoms
For aplastic anemia is characterized by a slowly progressive course with a tendency to transition to the chronic form with periods of exacerbations.
All clinical symptoms observed with aplastic anemia can be attributed to one of three main syndromes: anemic, hemorrhagic, or symptom-like complex of infectious complications. The appearance of signs of a syndrome is a consequence of the inhibition of one or several sprouts of blood formation.
The main complaints of patients with the development of signs of anemic syndrome due to insufficient levels of hemoglobin and red blood cells in peripheral blood are: severe weakness and decreased working ability, dizziness and tinnitus with hearing preservation, a feeling of lack of air and bouts of heart palpitations.
The first signs of hemorrhagic syndrome in a patient with aplastic anemia are the appearance of bruises and hematomas on the skin of non-traumatic origin. Patients with aplastic anemia often complain of nasal bleeding, as well as bleeding gums. With marked inhibition of the platelet hemopoietic sprout, hemorrhage to the brain may occur.
Symptoms of reducing the level of leukocytes, as one of the pathogenetic links of aplastic anemia, is a predisposition to diseases of an infectious nature. Such patients fall into the category of “frequently ill”, that is, during the year they have more than ten episodes of infectious diseases. A pronounced inhibition of leukocyte production provokes purulent-septic complications (ulcerative-necrotic tonsillitis, aphthous stomatitis, otitis media, felon, post-infectious abscesses, generalized sepsis).
Already during the initial examination of the patient, the characteristic symptoms of aplastic anemia can be identified: severe pallor and cyanosis of the skin with bruises that have no clear boundaries, and sometimes petechial rash. Increased borders of the liver and the appearance of edema of the lower extremities indicate the development of signs of heart failure. Auscultatory tendency to hypotension, sinus tachycardia and gross systolic murmur in all auscultatory points. An important diagnostic feature of aplastic anemia is an unchanged spleen.
The degree of manifestation of a symptom complex directly depends on the degree of inhibition of the hemopoietic sprouts. Severe aplastic anemia has the following diagnostic criteria: the level of neutrophils is less than 0.5 × 109 / l, platelets are less than 20 × 109 / l, the corrected increase in reticulocytes is less than 1%. If the patient has at least one of these criteria in combination with a pronounced decrease in the bone marrow cellularity, then this is the reason for establishing the patient’s diagnosis of severe hypoplastic anemia.
Aplastic anemia in children
In childhood, congenital types of aplastic anemia, which include Fanconi and Blackfen-Diamond anemia, make their debut.
Fanconi anemia is a hereditary pathology inherited in an autosomal recessive manner, that is, cases of the disease are observed only in families where both parents are carriers of the pathological gene. Fanconi anemia manifests itself not only in the deep oppression of all types of blood formation, but also in the appearance of developmental anomalies.
The debut of the disease occurs at the age of 4-12 years, but hematological problems may occur immediately after the birth of the child. Congenital anomalies include: mismatch of bone age with the passport, congenital defects of the cardiovascular system, microcephaly, anomalies of development of bone tissue, organs of the genitourinary system, the psychomotor lag. Hematological changes are manifested at a later age (on average, attaining 9 years of age) and the symptoms of a hemorrhagic symptom complex predominate in the clinical picture, after which the signs of leukocytopenia and erythrocytopenia progressively increase.
This pathology has a rapid progressive course, therefore, 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 treatment for congenital Fanconi anemia is bone marrow transplantation.
Anemia of Blackfire Diamond belongs to the group of sporadic hereditary blood pathologies and is characterized by the defeat of an exclusively red blood cell hemopoietic germ. The debut of the disease occurs during the first year of a child’s life.
Children with anemia of Blackfen-Diamond have a typical phenotype: pale skin, large upper lip, wide-set eyes, dry splitting hair, bone age lagging behind 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 for vital reasons red cell transfusion.
In childhood, acquired forms of aplastic anemia are extremely rare and manifest the same symptoms as in adults with the complete absence of congenital abnormalities.
If a child has signs of impaired hematopoietic function of the bone marrow, it is imperative that differential diagnostics be performed with such diseases as acute lymphoblastic and myeloblastic leukemia, megaloblastic anemia, hypersplenism syndrome, and metastatic bone marrow damage.
A child with suspected congenital aplastic anemia must be subject to a comprehensive examination, which includes: cytogenetic analysis after trepanobiopsy, a blood test for the presence of antibodies to blood cells, radiography with bone age, myelogram. All nearest relatives of a sick child are also subject to examination.
Aplastic anemia treatment
The key to a speedy recovery for 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 the selection of the appropriate treatment method in each case.
For the first time diagnosed aplastic anemia is the reason for hospitalization of the patient in the hospital, regardless of the severity of clinical manifestations and laboratory parameters.
In a situation where the etiopathogenetic factor that caused the development of aplastic anemia is known, treatment must begin with the removal of the root cause, in order to avoid further progression of hematopoietic suppression.
As therapeutic measures for diagnosed aplastic anemia, hematologists all over the world use the following methods: replacement transfusion of whole blood or its elements, bone marrow transplantation, as well as the use of drugs aimed at stimulating blood formation.
Replacement therapy of aplastic anemia involves the use of a replacement transfusion of suitable donor blood or its individual elements (platelet, red blood cell mass and granulocytes). This method of treatment is preventive, since a blood transfusion only replenishes the supply of necessary blood elements, but does not restore the function of blood formation in the bone marrow. In addition, with this form of aplastic anemia, as autoimmune, this method does not apply, because the introduction of foreign cells, the body begins to produce an immune response, which leads to treatment failure.
It should be borne in mind that repeated injections 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 taking drugs that promote the removal of iron from the body. In order to avoid the process of graft rejection before the procedure of bone marrow transplantation to a patient, it is unreasonable to apply blood transfusion.
The most effective and at the same time the most dangerous method of treatment of aplastic anemia is bone marrow transplantation, since only this method can be a trigger for normalizing the function of blood formation in the bone marrow. This method is used preferably at a young age of the patient after careful selection of a suitable donor, which can be the closest relative of the patient. Preparatory procedures for bone marrow stem cell transplantation are exposure of a patient to the patient’s high doses of radiation, as well as the use of chemotherapy drugs. The preparatory stage of the donor is blood sampling, filtering healthy stem cells from it and introducing them into the patient’s general circulation, through which they enter the bone marrow cavity, where proliferation of healthy blood cells occurs.
In order to avoid complications, the patient is prescribed drugs to prevent graft rejection, but it is not always possible to avoid this fatal situation for the patient. This method of treatment is expensive and requires compliance with certain conditions that are available only in specialized clinics, and therefore is not widely used as a therapy for aplastic anemia.
Patients with aplastic anemia of autoimmune genesis require the use of immunosuppressive drugs, the action of which is aimed at suppressing the inadequate functioning of the immune system. The drugs of choice in this situation are: Cyclosporin (daily dose of 10 mg / kg orally), Antithymocyte globulin (daily dose of 15 mg / kg intravenously) and Anti-lymphocyte globulin (daily dose of 130 mg intravenously). The use of immunosuppressants in most cases is accompanied by severe adverse reactions that threaten the patient’s life (anaphylactic shock, serum sickness, infectious diseases), to prevent 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 treatments for aplastic anemia, however, there are cases when a recurrence of the disease occurs after taking this group of drugs.
As an additional therapy to the main direction in the treatment of aplastic anemia, drugs are used that stimulate the hematopoietic function of the bone marrow, the so-called colony-stimulating factors (Molgrammostin, Filgrastim, Leucomax). Preparations of this group are effective in stimulating the proliferation of cells of the granulocyte series; therefore, their field of application is 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 drug administration is parenteral in a daily dose of 5 mg / kg. The limiting factor in the use of funds of this group is their high cost.
The stimulating effect of androgens on all sprouts of blood formation has been scientifically proven, and therefore, androgens are widely used in the treatment of aplastic anemia. These drugs are advisable to use only in the case of morbidity among men, and recommended long-term courses of drug administration (Testosterone propionate twice a day, 1 ml of 5% solution or prolonged preparation Sustanon – 250 1 ml 1 time per month).
Radical splenectomy is used as a palliative treatment, which in 85% of cases has a positive effect in the treatment of aplastic anemia. The pathogenetic validity of this method is that the removal of the spleen stops the sequestration of blood cells and sharply limits the production of antibodies against healthy bone marrow cells. 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 health of patients with signs of aplastic anemia directly depends on the severity of the disease and the depth of the decrease in the level of vital blood cells.
Unfortunately, to this day, world statistics show disappointing data regarding the death rate from aplastic anemia, regardless of how progressively the pharmaceutical industry is developing in relation 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 generalized form of sepsis, as the final stage of leukocytopenia.
Significantly improved predictions after the start of the use of radical treatment methods (bone marrow stem cell transplantation, use of immunosuppressants). In 50-90% of cases, the use of these methods of treatment can achieve full recovery of the patient.
The use of antithymocytic and anti-lymphocytic immunoglobulins in combination with therapy with cyclosporine allows only 60-70% of cases to achieve remission of the disease.