Aplastic anemia is an inhibition of the hematopoiesis function of the red bone marrow (erythrocytopoiesis, leukopoiesis and thrombocytopoiesis), leading to pangemocytopenia. The main clinical manifestations of the hematological syndrome include dizziness, weakness, fainting, shortness of breath, tingling in the chest, skin hemorrhages, bleeding, a tendency to develop infectious-inflammatory and purulent processes. The disease is diagnosed on the basis of characteristic changes in the hemogram, myelogram and histological examination of the trepanobioptate. Pathology treatment includes hemotransfusions, immunosuppressive therapy, and myelotransplantation.
D61 Other aplastic anemia
Aplastic (hypoplastic) anemia is a severe disorder of hematopoiesis (most often of all its links), accompanied by the development of anemic, hemorrhagic syndromes and infectious complications. It develops on average in 2 people per 1 million population per year. Pathology affects men and women with approximately the same frequency. The age peaks of morbidity occur at the age of 10-25 and older than 50 years. With this pathology, the formation of all three types of blood cell elements (erythrocytes, leukocytes and platelets) is more often disrupted in the bone marrow, sometimes only red blood cells; depending on this, true and partial aplastic anemia are distinguished. In hematology, this type of anemia is one of the potentially fatal diseases that lead to the death of 2/3 of patients.
Causes of aplastic anemia
By origin, aplastic anemia can be congenital (associated with chromosomal aberrations) and acquired (developed during life). It is generally believed that the inhibition of myelopoiesis is associated with the appearance of cytotoxic T-lymphocytes in the red bone marrow and blood, producing tumor necrosis factor and gamma interferon, which in turn suppress hematopoiesis sprouts. Various external factors (chemical compounds, physical phenomena, medicinal substances), as well as endogenous factors (viruses, autoimmune reactions) can trigger this mechanism. The most significant reasons include:
- Taking myelotoxic drugs. The connection of anemia with the administration of certain antitumor, anticonvulsant, antibacterial, antithyroid, antimalarial drugs, tranquilizers, gold preparations, etc., with a potential myelotoxic effect, has been reliably established. Medicinal substances can cause both direct damage to hematopoietic stem cells and indirect damage through autoimmune reactions. Anemia associated with such a mechanism of development is called medicinal.
- Contact with chemical and physical agents. Bone marrow suppression can be caused by interaction with organic solvents, arsenic compounds, benzene compounds, pesticides, irradiation of the whole body. In some cases, hematopoiesis insufficiency is temporary and reversible – the main factors here are the concentration /dose of the substance and the time of contact. bone marrow suppression.
- Viral infections. Of the viral agents, the greatest importance is given to the pathogens of hepatitis B, C and D. In this case, hypoplastic anemia usually develops within six months after viral hepatitis. When studying the pathogenesis, it was noticed that virus replication occurs in blood and bone marrow mononuclears, as well as in immune cells. It is assumed that the suppression of myelopoiesis in this case is a kind of immune response that occurs against cells carrying viral antigens on their surface. This type of anemia is isolated in a separate form – posthepatitis. Other viral infections include CMV, infectious mononucleosis, and influenza.
Cases of pancytopenia caused by infection with tuberculosis, intoxication, radiation sickness, lymphoproliferative diseases (thymoma, lymphoma, chronic lymphoblastic leukemia), pregnancy are also described. In almost half of the observations, the cause of anemia cannot be identified – such cases are attributed to the idiopathic form.
Aplastic anemia may be based on either primary damage to hematopoietic stem cells, or a violation of their effective differentiation. In hereditary anemia, hematopoiesis insufficiency is mediated by karyotypic aberrations, leading to a violation of DNA repair and the inability to replicate bone marrow stem cells. In the case of acquired anemia, under the influence of etiofactors, activation of T cells is observed, which begin to produce cytokines (interferon-gamma, TNF) that affect the progenitor cells of hematopoiesis. The expression of genes responsible for apoptosis and activation of cell death increases in bone marrow stem cells. The main clinical manifestations are caused by panhemocytopenia – a decrease in the composition of the blood of all its shaped elements (erythrocytes, leukocytes, platelets).
Classification of aplastic anemia
In addition to various etiological variants (medicinal, posthepatitis, idiopathic), there are acute (up to 1 month of course), subacute (from 1 to 6 months) and chronic (more than 6 months) forms of the disease. Anemia occurring with selective suppression of erythropoiesis is called partial red cell aplasia. Based on the severity of thrombotic and granulocytopenia, this form of anemia is divided into 3 degrees of severity:
- very severe (platelets less than 20,0×109 / l; granulocytes less than 0,2×109 /l)
- severe (platelets less than 20,0×109/l; granulocytes less than 0.5 x 109/l), according to trepanobiopsy – low bone marrow cellularity (less than 30% of normal)
- moderate (platelets more than 20,0×109/l; granulocytes more than 0.5 x 109/l)
Symptoms of aplastic anemia
The defeat of three hematopoietic sprouts (erythro-, platelet- and leukopoiesis) causes the development of anemic and hemorrhagic syndromes, infectious complications. The onset of aplastic anemia usually occurs acutely. Anemic syndrome is accompanied by general weakness and fatigue, pallor of the skin and visible mucous membranes, tinnitus, dizziness, tingling in the chest, shortness of breath during exercise.
The main manifestation of thrombocytopenia is hemorrhagic syndrome. Patients note the appearance of petechiae and ecchymoses on the skin, increased bleeding of the gums, spontaneous nosebleeds, menorrhagia. Hematuria, uterine and gastrointestinal bleeding may occur. The consequence of leukopenia and agranulocytosis is the frequent development of infectious processes – stomatitis, pneumonia, infections of the skin and urinary tract. Weight loss, lymphadenopathy, hepatomegaly and splenomegaly are not typical for aplastic anemia – with these signs, another cause of panhemocytopenia should be sought.
Congenital aplastic anemia (Fanconi syndrome) usually develops in children under the age of 10 years and, in addition to bone marrow aplasia, is characterized by other disorders: microcephaly, kidney hypoplasia, stunting, abnormalities in the development of the upper extremities (hypoplasia of the first metacarpal and radius), hypospadias, hyperpigmentation of the skin, extreme hearing loss, etc. With hereditary anemia of Estren-Dameshek, there is a total lesion of hematopoiesis and pancytopenia in the absence of congenital malformations. Diamond-Blackfen anemia or partial red cell aplasia is characterized only by a decrease in the number of red blood cells.
The fatal outcome can be caused by hemorrhages in internal organs, massive bleeding, infectious complications, anemic coma. The most threatening of hemorrhagic complications is hemorrhage in the brain (hemorrhagic stroke). Patients are prone to frequent and severe viral and bacterial infections of the respiratory tract. A significant or rapid decrease in the level of red blood cells can lead to an anemic coma. With a lightning-fast form, severe anemia, immunodeficiency, coagulopathies with fatal consequences develop extremely quickly.
Assessment of hematological status includes careful clinical examination and thorough laboratory diagnostics. Physical examination reveals pronounced pallor or jaundice of the skin, arterial hypotension, tachycardia. The basis of the diagnostic algorithm is the general and biochemical blood analysis, sternal puncture, trepanobiopsy:
- Blood tests. For hemograms with hypoplastic anemia, erythro-, leukocyte- and thrombocytopenia, neutropenia and relative lymphocytosis are typical. Evaluation of biochemical parameters (liver samples, nephrological complex, serum iron, bilirubin) is informative to exclude other anemias.
- Examination of bone marrow punctate. The myelogram shows a decrease in the number of myelocaryocytes and megakaryocytes, a decrease in cellular activity. In trepanobioptate, the replacement of red bone marrow with fat (yellow) is determined.
As part of the diagnostic search, aplastic anemia must be differentiated from megablastic (B12-deficient, folate-deficient) anemia, idiopathic thrombocytopenic purpura, paroxysmal nocturnal hemoglobinuria, acute leukemia.
Treatment of aplastic anemia
Patients with aplastic anemia are hospitalized in specialized departments. They are provided with complete isolation and aseptic conditions to prevent possible infectious complications. Effective treatment is a complex problem of practical hematology. Depending on the level of cytopenia , the following therapeutic approaches are used:
- Immunosuppressive therapy. With moderate cytopenia, pharmacotherapy is prescribed, including a combination of antithymocytic immunoglobulin and cyclosporine A. Maintenance therapy is carried out with anabolic steroids or their combination with cyclosporines.
- Blood transfusion. In combination with a course of immunosuppressive therapy with low red blood counts, replacement hemotransfusion therapy (transfusion of platelets and erythrocyte mass), plasmapheresis is indicated. This measure has no effect on the pathogenetic link of the disease, but it makes it possible to make up for the deficiency of blood cells not produced by the bone marrow.
- Transplantation of BM and SC. The most favorable prognoses for long-term survival are provided by performing allogeneic bone marrow transplantation. However, due to the complexity of selecting an immunologically compatible donor, the procedure is used only to a limited extent. Autologous transplants and peripheral blood stem cell transplantation are considered as experimental approaches. Splenectomy, endovascular occlusion of the splenic artery may be indicated for patients with a mild form of anemia.
Prognosis and prevention
The prognosis is determined by the etiological form, severity and severity of anemia. The criteria for an unfavorable outcome are rapid progression of the disease, severe hemorrhagic syndrome and infectious complications. After bone marrow transplantation, remission can be achieved in 75-90% of patients. Primary prevention of this type of anemia involves the exclusion of the influence of adverse environmental factors, unreasonable use of drugs, prevention of infectious morbidity, etc. Patients with an already developed disease require follow-up by a hematologist, systematic examination and long-term supportive therapy.