Aplastic anaemias

Aplastic anaemia - a condition characterised by depression of hemopoietic activity (depression) of an osteal brain with development along with an anaemia also a leucocyte - and thrombocytopenias.

Aetiologies and a pathogenesis. The aplastic anaemia can educe at influence of some myelotoxic factors: an ionising radiation, chemical materials - benzene, salts of gold, arsenic; medical products - Chloramfenicolum (Levomycetinum), Phenylbutazonum (Butadionum), Chlorpromazinum (aminosyn), Meprobamatum, Dilantinum, antimetabolites (β-Mercaptopurinum, Methotrexatum), alkylating (Cyclophosphanum, Chlorbutinum) and some other agents. The myelotoxic effect from influence of one factors (an ionising radiation, antimetabolites) arises always at enough big dose, others - shows individual. The cause of individual sensitivity, in particular to some medical products is not always clear, but can be bound to genetical defects of hemopoietic cells. It concerns, for example, Chloramfenicolum and Phenylbutazonum, which cause a suppression (depending on a dose) an erythrogenesis with frequency accordingly 1:24000 and 1:40000 persons, their accepting. Hereditary character of individual sensitivity of erythropoietic cells to the given medicinal materials proves to be true development of an aplasia of an osteal brain in different members of one monogynopaedium and in unioval twins. In other cases communication of the oppression of a hemopoiesis induced by medicinal materials with immune mechanisms appearance of antibodies to erythrocyte precursors is probable. Cases of occurrence of an aplastic anaemia after an acute virus hepatitis (probably, owing to ability of a virus of a hepatitis to variate a karyotype of cells that has been tracked on culture of leucocytes), tolerated infection contamination Epstein-Barr Virus, are described by a parvovirus.

There is also a hereditary form of an aplastic anaemia - anaemia Fanconi.

More than at half of patients it is not possible to tap any causative factors are a so-called idiopathic aplastic anaemia. The mechanisms underlying the idiopathic form of an anaemia, are obscure. The autoimmune mechanism bound to influence on cells of an osteal brain of autoantibodies with the assistance of immune lymphocytomas is possible. It is shown, that lymphocytes (T - suppressors) patients inhibit formation erythrocyte colonys of an osteal brain of the donor and can break differentiation and a proliferation of hemopoietic precursors.

Assume also, that the lesion (internal defect) of founder cell to what restoration of a hemopoiesis at patients after transplantation of the allogenic osteal brain containing normal founder cells by it testifies can be a basis of an aplastic anaemia. There are the experimental data testifying to value for development of aplastic process and disturbances of a microenvironment - primary defect of stromal cells of an osteal brain. However the short of these cellular defects remains obscure, as well as their primacy. Probably, that at different forms of an aplastic anaemia pathogenetic mechanisms dissimilar.

Clinical picture. The idiopathic aplastic anaemia can acutely begin and have quickly progressing flow, but more often illness educes gradually. Clinical implications depend on expression of a cytopenia. At physical research pallor of integuments, a dyspnea, a tachycardia become perceptible, systolic hum in the field of heart is auscultated. The hemorrhagic syndrome corresponds to thrombocytopenia degree, petechial enanthesises and mucosas, a staxis of gums, nasal and uterine bleedings are observed. A neutropenia consequence are infectious complications - anginas, a pneumonia, an infection contamination of urinary pathes, a sepsis. The lien usually is not enlarged.

Datas of laboratory. Hematological signs of an aplasia of an osteal brain are the expressed anaemia (concentration of haemoglobin can drop to 20 - 30 g/l), a leukopenia (a neutropenia with a relative lymphocytosis) and a thrombocytopenia, sometimes before full disappearance of thrombocytes from blood. The anaemia more often normochromic and macrocytic 94 microns ' becomes perceptible approximately at 60 - 65 % of patients), number of reticulocytes are lowered. The iron maintenance in blood serum normal or raised, transferrin saturation close to 100 %. Rising of level of haemoglobin and erythropoetin (as production of erythrocytes is sharply lowered or there is an erythropoetin inhibitor, or the osteal brain is tolerant to it) In some cases becomes perceptible. An ESR it is usually enlarged to 40 - 60 mm/ch.

At a puncture biopsy of an osteal brain receive small quantity of myelocariocytes or they absolutely are absent, at histological research note replacement of a hemopoietic tissue by a fatty tissue, However even if a biopsy effect in different places it does not reflect a condition of all osteal brain: on autopsy often find the islets of a hemopoiesis (neogenesis) keeping two-nuclear and multinuclear erythroidal cells, among considerably exhausted osteal brain.

At fast advance of illness the mors can come in some months, at chronic flow there is a change of an exacerbation and remissions. Full recover is sometimes observed.

Aplastic anaemia Fanconi - the hereditary, often family anomaly transferred on autosomal -recessive type; it is taped at children at the age from 4 till 10 years, it is characterised, besides an aplasia of an osteal brain and a pancytopenia, also nearby of somatic and metabolic disturbances: a growth inhibition, defects of formation of an atomy, a nanocephalia, a hypogonadism, a hypoplasia of nephroses, an aminoaciduria, a glucosuria, a skin hyperpegmentation. Changes of indicators of blood are often less expressed, than at the idiopathic form of an aplastic anaemia. Predilection to development of an acute leukosis is observed.

Diagnosis and the differential diagnosis. An aplastic anaemia assume at depression in blood of quantity of erythrocytes, leucocytes and thrombocytes (pancytopenia). Differential diagnostics should be spent with an acute leukosis and В12-a scarce anaemia. The sternal puncture has great value: at detection of a hyperplasia of an erythrocyte sprout the aplastic anaemia is excluded. If the erythroidal elements enlarged in quantity have morphological lines of megaloblasts presence at patient В12-scarce anaemia is probable, but thus it is necessary to mean and erythremic myelosis possibility. Presence at a medullar punctate of a considerable quantity of blast cells testifies to an acute leukosis. Reception at a puncture of a poor stuff cannot be regarded yet as the indicating on an aplasia of an osteal brain as such picture happens and at an acute aleukemia. For diagnosis specification effect a bone trepanobiopsy; Reduction of an active hemopoietic osteal brain and augmentation of a fatty tissue confirms the diagnosis of an aplastic anaemia.

Aplastic anaemia is necessary for differentiating and with an immune peripheric cytopenia. For diagnostics of an immune cytopenia matter detection of the enlarged lien, positive Coombs test, normal quantity of megacaryocytes in an osteal brain.

Delimitation of an aplastic anaemia from a night hemoglobinuria and forms of an autoimmune hemolitic anaemia is based on absence at an aplastic anaemia of signs of an intravascular hemolysis, a reticulocytosis, lien augmentation.

Treatment and the forecast. Treatment is referred on correction cytopenia both medullar insufficiency and struggle against complications. In the beginning cancel all medical products to which the patient has an individual hypersensitivity and which can be involved in anaemia development. At a serious anaemia spend replaceable transfusions of the washed erythrocytes, at the expressed thrombocytopenia and hemorrhages - platelet concentrate transfusions (it is better from one donor). At infectious complications apply antibiotics of a wide action spectrum.

Most perspective method of treatment of an aplastic anaemia is transplantation allogenic compatible on NEA - to antigens of an osteal brain. Transplantation of an osteal brain is shown persons of young age, especially with serious, prognostically unfavorable forms of illness. Transplantation in the presence of the suitable donor should be early when the alloimmunization owing to replaceable therapy is still insignificant (more in detail about transplantation).

In cases of impossibility of transplantation treatments by Prednisolonum in high doses (60 make an attempt - 80 mg/days), give to drink absence of effect - in small doses, basically with the haemostatic purpose.

A number of patients (according to some information, more than at half) has successful a splenectomy (in connection with excision of the organ developing antibodies). The splenectomy is shown at less serious forms of illness - absence of the big staxis and sepsis signs. The effect comes through 2 - 5 months after operation, but the staxis usually decreases at once. After a splenectomy spend treatment by anabolic hormones (Nerobolum on 20 mg/sut, anapolon on 200 mg/sut during half a year).

To treatment of an aplastic anaemia apply also antilymphocytic globulin, according to foreign authors, use of commercial antilymphocytic globulin effectively at 40 - 50 % of patients that allows to recommend it at early stages of treatment. By experience of domestic hematologists antilymphocytic globulin is expedient for prescribing after a splenectomy (at its inefficiency or as supporting therapy), the rabbity and goat antilymphocytic globulin of a domestic production introduce intravenously on 120 - 160 mg 10 - 15 times.