Aplasticheskaya anemia
Under aplastic anemia understand the state, developing as a result of bone marrow suppression in bone marrow and no signs of hemoblastosis characterized by pancytopenia. The concept of aplastic anemia regarded as syndromic, as the prevalence of fat in the bone marrow when pancytopenia in peripheral blood occurs in a number of diseases, different nature.
Of the group of congenital aplastic anemia should be allocated constitutional Fanconi anemia. The group acquired aplastic anemia include anemia, associated with the intake of large doses tsitostati- cal drugs, arising after acute viral hepatitis.
The etiology and pathogenesis of aplastic anemia
Describes aplastic anemia, occurring after medication, not causing. For most people,, that adopt them, changes in blood. These include chloramphenicol, ʙutadion (phenylbutazone), gold compounds, butamyd (tolbutamid), sulьfapiridazin (sulьfametoksipiridazin, kineks), meprotan (meprobamate, andaksin), trimetin (trimethadione), ʙukarʙan (karʙutamid), aminazin (chlorpromazine) and etc.
The most common form of idiopathic aplastic anemia, in which the most thorough survey of the patient does not allow to find out the cause of the disease.
In principle, the following mechanisms of aplastic anemia:
1. Reducing the number of stem cells or their internal defect.
2. Violation of the microenvironment, leading to dysfunction of stem cells.
3. External humoral or cellular effects, basically immune, disrupts the normal function of stem cells.
There is some evidence, allowing to speak about predisposition to the development of aplasia in patients, taking chloramphenicol. We describe two cases of aplastic anemia identical twins after receiving chloramphenicol, suggesting the possibility of a genetic predisposition to this disease. Based on the study of DNA synthesis in vitro bone marrow of patients, had undergone hloramfinikolovuyu aplasia, and his relatives, it was concluded a genetic predisposition to hloramfinikolovoy aplasia. Greater sensitivity to chloramphenicol in vitro bone marrow of the patient compared with the donor revealed no, though, probably, a genetic predisposition to the action of chloramphenicol still exists. There are cases of family increased sensitivity to the development of aplasia in patients, receiving gold preparations.
Aplastic anemia may occur by exposure to ionizing radiation, while there is the death of stem cells. There is a clear dose-dependency.
The mechanism of aplasia after viral infection also not clear enough. It develops most often after suffering a hepatitis A or hepatitis B, It does not belong to the group A, nor the group B.
There are cases of aplasia after infectious monokuleoza. Not found, whether the virus directly affects stem cell or a situation arises geteroimmunnaya: antibodies against the virus, fixed stem cells, cause the death of stem cells.
There is some information on the pathogenesis of the constitutional form of aplastic anemia, or Fanconi anemia. In patients with Fanconi anemia, pancytopenia observed in addition to the other signs of pathology - hyperpigmentation, lack or decrease thumbs, no radius, changes in the kidneys, heart. Inherited diseases autosomnoretsessivnoe, It is shown in homozygous carriers usually over the age of 5 years, sometimes immediately after birth.
According to scientists, by culturing the bone marrow of patients with Fanconi anemia prior to its sharply reduced the number of CFU-S and CFU-E. Most likely, Fanconi anemia when there is a defect in stem cells. Proved, that neither the serum of patients with Fanconi anemia, nor their lymphocytes do not affect the culture of bone marrow donors.
Installed defect in the DNA repair system in fibroblasts from patients with Fanconi anemia. Maybe, that is connected to a light defect in the Fanconi anemia chromosomes under the influence of ultraviolet radiation, low doses of cytotoxic drugs. It is suggested, that light defect and mutability of DNA leads to the development of both aplasia, and to the emergence of these patients with acute leukemia.
A very large number of studies, especially in recent years, devoted to the study of the pathogenesis idiopathic aplastic anemia. Established, that with aplastic anemia decreases as the number of colony-forming cells in the bone marrow, and peripheral blood. There has been a decrease in the number of both erythroid, and granulocyte colony. These data suggest defeat one way or another stem cell hematopoiesis.
In favor of the destruction of stem cells in aplastic anemia demonstrates the effectiveness of bone marrow transplants from identical twins and siblings, HLA-compatible system. However, the question of, what nature of the violation found in stem cell, It remains open. Currently available evidence for effects on stem cell immune lymphocytes. On the immune nature of aplastic anemia indicated by the absence in many cases the effect of engraftment of transplanted bone marrow identical twins without prior immunnodepressii.
A large number of studies have been devoted study the effects of different lymphocyte populations stem cells. Proved, that the cells of patients with aplastic anemia inhibit the formation of erythroid colonies of bone marrow, and then, they may interfere with the differentiation and proliferation of bone marrow cells. A decrease in the aplastic anemia helper T-lymphocyte function.
All these data support the probability of involvement of immune mechanisms in the development of aplastic anemia, a significant number of patients. However, it is not established, which of these mechanisms are the primary, and which are joined in the disease. Currently methods, by which try to divide aplastic anemia, immune and non-immune to, very imperfect. Perhaps there are different forms of aplastic anemia Pathogenesis. In some cases, there is an internal defect in stem cell, in others - the microenvironment in the third - the suppression of hematopoiesis immune lymphocytes. However, more likely, that much of aplastic anemia refers to a group of immune. Proof of this is the detection method agregatgemagglyutinatsii the majority of patients with aplastic anemia on the peripheral surface of the red blood cell antibodies, belonging to the class IgG. It is possible the participation of these antibodies in the destruction of stem cells by the mechanism of antibody-dependent cytotoxicity, however possible, These antibodies appear a second time and have no relation to the pathogenesis of aplastic anemia.
Clinical manifestations of aplastic anemia
Clinical manifestations of idiopathic aplastic anemia may be different. In some cases, the disease begins acutely, rapidly progressing and almost defies any treatment. But more often the disease begins gradually, the patient adapts to anemia and go to the doctor only when a significant expression of pancytopenia. The clinical picture is characterized by anemia, bone marrow suppression of varying severity, thrombocytopenia with all symptomatic thrombotic syndrome (bruising, petechiae on the skin, Nasal, gingival bleeding, menorragii). Often there is a significant degree of severity of neutropenia, a consequence of which is part of pneumonia, otitis, pyelitis and other inflammatory processes. Sometimes hematoma abscess. Often there is sepsis. Anemia is caused as a violation of the formation of red blood cells, and bleeding.
On examination, attention is drawn to the expressed pallor, often on the skin are hemorrhage. Characterized by inflammatory changes of the oral mucosa. When listening to the heart often found systolic murmur. When idiopathic form of the disease is not palpable spleen. It can be increased by gemosideroze, develops as a result of massive transfusions of red blood cells. Possible enlargement of the liver due to circulatory failure due to anemia.
In some cases, the disease progresses rapidly and in a few weeks or months leading to death, Other - proceeds chronically, with periodic exacerbations and remissions. Sometimes there comes a full recovery.
Laboratory indicators of aplastic anemia
Severe anemia can be very significant. Sometimes hemoglobin decreases to 1,24-1,86 mmol / l (20-30 G / l). Anemia often normochromic. The content ranges from reticulocytes 0 4-5 %. Severe forms of the disease occur at lower levels of reticulocytes. Characterized by severe granulocytopenia. Sometimes granulocyte count drops to 0,2 T in 1 l, The most frequently develop infectious complications. Perhaps the decline in the absolute number of monocytes. The absolute level of lymphocytes in most cases remains normal. The platelet count is always reduced, sometimes they can not determine when counting. At the same time is prolonged bleeding, developing hemorrhagic syndrome. In most patients, the ESR increases to 30-50 mm / hr.
Reduces the number of bone marrow myelokaryocytes. In some patients the stimulation of red germ hematopoiesis. It increased the number of lymphocytes, plasma cells, tissue basophils. Megakaryocytes may be completely absent. In the bone marrow dramatically increases the amount of iron, located in erythrokaryocytes. and extracellularly.
Histological examination of the bone marrow in some cases there is a complete disappearance of bone marrow elements, in others - there are small pockets of hematopoiesis in the background of a significant devastation of the bone marrow.
The iron content of serum increased in most patients, transferrin saturation approaches 100 %. In the study using radioactive ferrokinetiki iron excretion detected lengthening the time of its plasma and decrease the amount of iron, included in erythrocytes. The lifespan of red blood cells, measured using radioactive chromium, often shortened, less normal. Sometimes increases the level of fetal hemoglobin. Study of agregatgemagglyutinatsii often gives a positive result.
Diagnosing Anemia aplasticheskoй
Aplastic anemia can be diagnosed only after histological examination of the bone marrow. Detection of peripheral blood pancytopenia warrants sternal puncture to exclude Leukemia & B12-deficiency anemia. The next obligatory stage of diagnosis is biopsy. Upon detection of a large amount of fat in the bone marrow aplastic anemia diagnosed.
If trepanobiopsy found the normal ratio between the fat and hematopoietic tissue or hyperplasia, diagnosed with aplastic anemia disappears. In these cases, it is first necessary to eliminate the peripheral form of autoimmune pancytopenia, which is characterized by the presence of antibodies, directed against the red blood cells, peripheral platelet and neutrophil granulocytes. This often increases the spleen, sometimes positive Coombs, but most of the antibodies detected by agregatgemagglyutinatsii. The number of megakaryocytes in the bone marrow of normal, whereas aplastic anemia are almost completely absent. When peripheral pancytopenia in the elderly and in people, resection of the stomach, should first eliminate B12-deficiency anemia, and the children - folievodefitsitnoy anemia.
Signs of intravascular hemolysis (gemosiderinuriya, increase in plasma free hemoglobin, the appearance of black or red urine with high protein content, reticulocytosis) favors or paroxysmal nocturnal hemoglobinuria, or hemolysin form autoimmune hemolytic anemia, combined with neutropenia and thrombocytopenia. Correct diagnosis makes use of samples Hema, sucrose samples in three variants and a method agregatgemagglyutinatsii.
