Aplastic anemia (hypoplastic anemia): causes, symptoms, diagnosis, treatment

Aplastic anemia (hypoplastic anemia) - normochromic-normocytic anemia, is the result of depletion of the reserve of hematopoiesis precursors, which leads to bone marrow hypoplasia, a decrease in the number of red blood cells, white blood cells and platelets. Symptoms of the disease are caused by severe anemia, thrombocytopenia (petechiae, bleeding) or leukopenia (infection). The diagnosis requires the presence of peripheral pancytopenia and the absence of precursors of hemopoiesis in the bone marrow. For treatment, use horse antitimotsitarny globulin and cyclosporine. The use of erythropoietin, granulocyte-macrophage colony-stimulating factor and bone marrow transplantation can be effective.

The term "aplastic anemia" implies bone marrow aplasia, which is associated with leukopenia and thrombocytopenia. Partial erythroid aplasia is limited by the pathology of the erythroid series. Although these two diseases are quite rare, aplastic anemia is more common.

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Causes of the aplastic anemia

Typical aplastic anemia (most common in adolescents and young adults) is idiopathic in about 50% of cases. It is known that it can be caused by chemical compounds (for example, benzene, inorganic arsenic), radiation or drugs (eg, cytostatics, antibiotics, nonsteroidal anti-inflammatory drugs, anticonvulsants, acetazolamide, gold salts, penicillamine, quinacrine). The mechanism is unknown, but the manifestations of selective hypersensitivity (possibly genetic) are the basis for the development of the disease.

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Symptoms of the aplastic anemia

Although the onset of aplastic anemia is gradual, often weeks and months after exposure to toxins, it can sometimes be acute. Symptoms depend on the severity of pancytopenia. The severity of symptoms and complaints characteristic of anemia (for example, pallor) is usually very high.

Severe pancytopenia causes petechiae, ecchymosis and bleeding gums, haemorrhage in the retina and other tissues. Agranulocytosis is often accompanied by life-threatening infections. Splenomegaly is absent until it is induced by transfusion hemosiderosis. Symptoms of partial erythroid aplasia are usually less intense than aplastic anemia, and depend on the degree of anemia or concomitant diseases.

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Forms

A rare form of aplastic anemia is Fanconi anemia (a type of family aplastic anemia with skeletal bone anomalies, microcephaly, hypogonadism and brown skin pigmentation) that occurs in children with chromosomal aberrations. Fanconi anemia is often hidden until there are accompanying diseases (often acute infectious or inflammatory diseases) that cause peripheral pancytopenia. Together with the elimination of concomitant diseases, the peripheral blood parameters normalize, despite the decrease in the cellular composition of the bone marrow.

Partial erythroid aplasia can be acute and chronic. Acute erythroblastopenia - the disappearance of the precursors of erythropoiesis from the bone marrow during an acute viral infection (especially parvovirus), is more common in children. The duration of anemia is greater the longer the acute infection. Chronic partial erythroid aplasia is associated with hemolytic diseases, thymoma, autoimmune processes and less often with drugs (tranquilizers, anticonvulsants), toxins (organic phosphates), riboflavin deficiency and chronic lymphocytic leukemia. A rare form of congenital anemia of Diamond-Blackfen usually occurs during the infancy, but can be in adulthood. This syndrome is accompanied by abnormalities of the bones of the fingers and low growth.

[8], [9], [10], [11], [12], [13]

Diagnostics of the aplastic anemia

Aplastic anemia is suspected in patients with pancytopenia (eg, leukocytes <1500 / μl, platelets <50,000 / μl), especially at a young age. The presence of partial erythroid aplasia is assumed in patients with anomalies of the bones of the skeleton and normocytic anemia. If anemia is suspected, bone marrow examination is necessary.

In aplastic anemia, erythrocytes are normochromic-normocytic (sometimes border-macro-cytopic). The number of leukocytes is reduced, mainly granulocytes. The platelet count is often less than 50,000 / μL. Reticulocytes are reduced or absent. Serum iron is increased. The cellularity of the bone marrow is sharply reduced. With partial erythroid aplasia, normocytic anemia, reticulocytopenia and elevated serum iron levels are determined, but with normal white blood cell and platelet counts. Cellularity and maturation of bone marrow can be normal, except for the absence of erythroid progenitors.

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Treatment of the aplastic anemia

In aplastic anemia, the therapy of choice is the administration of equine antitumocyte globulin (ATG) from 10 to 20 mg / kg, diluted in 500 ml of saline and administered intravenously for 4 to 6 hours for 10 days. Approximately 60% of patients respond to such therapy. Allergic reactions and serum sickness can be observed. All patients need to perform a skin test (to determine allergy to horse serum), additionally prescribed glucocorticoids (prednisolone 40 mg / m ² inside daily for 7-10 days or until the symptoms of complications decrease). Effective therapy is the use of cyclosporine (5 to 10 mg / kg orally daily), which causes a response in 50% of patients who did not respond to ATG. The most effective combination is cyclosporine and ATG. In the presence of aplastic anemia of superheavy form and the absence of a response to the course of ATG / cyclosporin, bone marrow transplantation or cytokine treatment (EPO, granulocyte or granulocyte-macrophage colony-stimulating factors) can be effective.

Performing stem cell or bone marrow transplantation can be effective in young patients (especially younger than 30 years), but requires the presence of a twin HLA-compatible sibling or skin of an unrelated donor. When making a diagnosis it is necessary to conduct HLA-typing of siblings. Since transfusions impair the effectiveness of subsequent transplantation, blood products should be prescribed when absolutely necessary.

The cases of successful use of immunosuppressive therapy (prednisolone, cyclosporine or cyclophosphamide) with partial erythroid aplasia are described, especially when suspicion of the autoimmune mechanism of the disease. Since in patients with partial erythroid aplasia against thymoma, the condition improves after thymectomy, KT is used to look for a similar focus and the question of surgical treatment is being considered.