What is Aplastic Anemia?
By aplastic anemia, we mean a group of pathological conditions in which, along with pancytopenia, a decrease in blood formation in the bone marrow is detected and there are no signs of hemoblastosis. Aplastic anemia is rather an independent form, not a syndrome. From the group of aplastic anemias constitutional Fanconi anemia is clearly distinguished. Among the majority of acquired aplastic anemia, forms with a sufficiently learned etiology are isolated. These include aplastic anemia, triggered by exposure to ionizing radiation or caused by taking excessively large doses of cytostatics.
A special group of aplastic anemia occurs after acute viral hepatitis. Described aplastic anemia after taking the drugs, which in most people do not cause any changes in the blood. Such drugs include chloramphenicol (chloramphenicol), phenylbutazone (butadione), gold compounds, tolbutamide (butamide), sulfamethoxypyridazine (sulfapyridazine, kinex), meprobamate (meprotan, andaxin trimethadione (trimethine), carbutamide (carcumin), and recurrent.
Fatal aplastic anemia is 10 times more common in people who take chloramphenicol. The most common idiopathic forms of aplastic anemia, where with the most careful examination of the patient can not figure out the cause of the disease.
Causes of Aplastic Anemia
In principle, the following mechanisms for the development of aplastic anemia are possible: a decrease in the number of stem cells; violation of the microenvironment, leading to a change in the function of stem cells; external humoral or cellular effects, mainly immune, disrupting the normal function of the stem cell.
Ionizing radiation can cause aplastic anemia; it clearly depends on the dose of radiation. At the same time, stem cell death is observed.
The mechanism for the development of aplasia after viral infection is also not clear enough. Aplasia develops more often after hepatitis A or hepatitis, not belonging to either group A or group B. Cases of aplasia after infectious mononucleosis and 2 cases of bone marrow transplantation to identical twins with post-hepatitis aplasia are described. In one case, the effect of transplantation was noted, in the other, the bone marrow did not survive; preparation with cyclophosphamide was required, and after it transplantation was successful. It does not answer the question whether the virus directly affects the stem cell or there is a heteroimmune mechanism for the development of aplasia (antibodies against a virus fixed on the stem cell cause the death of this stem cell).
The effectiveness of bone marrow transplantation from identical twins and siblings compatible with the HLA system speaks in favor of stem cell damage in aplastic anemias.
The lack of engraftment of the transplanted bone marrow from an identical twin without prior immunodepression testifies to the immune nature of aplastic anemia in a number of patients.
Symptoms of Aplastic Anemia
The clinical picture of idiopathic aplastic anemia may be different. Sometimes the disease begins acutely and progresses very quickly, almost does not respond to any therapy. But more often it begins gradually, the patient adapts to anemia and turns to the doctor when the severity of pancytopenia is significant. The clinical picture of hematopoiesis depression consists of anemia of various depths, thrombocytopenia with all clinical manifestations of thrombocytopenic syndrome (such as bruises, petechial rashes on the skin, nasal, gingival bleeding, uterine bleeding). Often, pneumonia, ear inflammation and other inflammatory processes become a consequence of severe neutropenia. Sometimes bruises, hemorrhages suppurate, infection of the organism is possible.
Anemia in patients is associated both with impaired red blood cell formation and bleeding.
For such patients, pallor is characteristic, skin hemorrhages, inflammatory changes on the mucous membrane of the rectum mouth are specific enough.
The doctor when listening to the heart reveals a systolic murmur. In the idiopathic form of the disease, the spleen is not palpable. Its increase is noted already at hemosiderosis as a result of massive transfusions of erythrocytes. An enlarged liver may be associated with circulatory failure in anemia.
In some cases, the disease progresses rapidly and in a few weeks or months leads to death, in others it occurs chronically, with periodic exacerbations and improvements. Sometimes there is a full recovery.
Diagnosis of Aplastic Anemia
Anemia is very severe, sometimes hemoglobin is reduced to 20-30 g/l. Anemia often normochromic, macrocytic. The content of reticulocytes ranges from 0 to 4-5%. Severe forms are accompanied by a large decrease in reticulocyte levels. Erythrokaryocytes in peripheral blood rarely appear. There is marked granulocytopenia. Sometimes the number of granulocytes is reduced to 0.2 × 109 / l, while infectious complications develop. Sometimes the absolute number of monocytes decreases. The absolute level of lymphocytes in most cases remains normal. The number of platelets decreases, while the bleeding time is significantly lengthened and, as a result, the hemorrhagic syndrome develops, the ESR accelerates to 30-50 mm/h.
The number of bone marrow myelokaryocytes decreases markedly. Sometimes there is irritation of the red sprout. The number of lymphocytes, plasma, mast cells is increased. Megakaryocytes may be completely absent. In the bone marrow, there is a sharp increase in the amount of iron located in both the erythrocaryocytes and extracellularly.
The serum iron content in most patients is increased, transferrin saturation approaches 100%. In the study of ferrokinetics with the help of radioactive iron, prolonged elimination of iron from plasma and a decrease in the amount of iron incorporated into red blood cells are detected. The life span of erythrocytes, measured with radioactive chromium, is most often shortened, less often – normal. Sometimes the level of fetal hemoglobin increases. Aggregate hemagglutination test is often positive. IgG is detected on the surface of red blood cells. It is necessary to exclude the presence of alloantibodies on the surface of recently transfused red blood cells.
Diagnosis of aplastic anemia is possible only after a histological examination of the bone marrow. Detection of pancytopenia in the peripheral blood serves as an indication for sternal puncture (bone marrow puncture produced through the anterior wall of the sternum) to exclude hemoblastosis and vitamin B12-deficiency anemia. After that, a study of the material taken. If a large amount of fat is detected in the bone marrow, aplastic anemia is diagnosed. If the study reveals a normal relationship between hematopoietic tissue and fat, or there is a structural increase in cells, then the diagnosis of aplastic anemia disappears. At the same time, the spleen often increases, sometimes there is a positive Coombs test, but more often antibodies are detected with the help of an aggregate hemagglutination test. In the bone marrow, the normal number of megakaryocytes, whereas in aplastic anemia, the megakaryocytes are almost completely absent. In case of peripheral pancytopenia in the elderly, in individuals with removal of part of the stomach, vitamin-B12-deficient anemia should be primarily excluded, in children, folide deficiency anemia.