Aplastic anemia – the oppression of function of blood formation of red marrow (an eritrotsitopoez, a leykopoez and a trombotsitopoez) bringing to pan-haemo cytosinging. Dizziness, weakness, faints, short wind, a pricking in breasts, skin gemorragiya, bleedings, tendency to development of infectious and inflammatory and purulent processes belong to the main clinical manifestations of a hematologic syndrome. The disease is diagnosed on the basis of characteristic changes of a gemogramma, miyelogramma and a histologic research of a trepanobioptat. Treatment of pathology includes carrying out hemotransfusions, immunosupressivny therapy, a miyelotransplantation.
Aplastic (hypoplastic) anemia – the heavy frustration of a hematopoiesis (is the most often than its links) which is followed by development of anemichesky, hemorrhagic syndromes and infectious complications. Develops on average at 2 people on 1 million population a year. Approximately with an identical frequency pathology affects men and women. The age peaks of incidence fall on age 10–25 and 50 years are more senior. At this pathology in marrow formation of all three types of cellular elements of blood (erythrocytes, leukocytes and platelets), sometimes - only one erythrocytes is more often broken; depending on it distinguish true and partial aplastic anemia. In hematology this type of anemia is among potentially fatal diseases leading to death of 2/3 diseased.
By origin aplastic anemia can be congenital (connected with chromosomal aberrations) and acquired (developed during life). It is considered to be that oppression of a miyelopoez is connected with emergence in red marrow and blood of the cytotoxic T-lymphocytes making a factor of a necrosis of tumors and γ-interferon, which in turn suppress blood formation sprouts. Can start this mechanism various vneshnesredovy (chemical compounds, the physical phenomena, medicinal substances), and also endogenous factors (viruses, autoimmune reactions). Carry to number of the most significant reasons:
- Reception of miyelotoksichesky medicines. Connection of anemia with reception of some antineoplastic, anticonvulsive, antibacterial, antitireoidny, antimalarial medicines, tranquilizers, gold medicines, etc., having potential miyelotoksichesky effect is authentically established. Medicinal substances can cause both direct damage of stem haematogenic cells, and mediated - through autoimmune reactions. The anemias connected with such mechanism of development are called medicinal.
- Contact with chemical and physical agents. Of marrow interaction with organic solvents, compounds of arsenic, benzene connections, pesticides, radiation of all body can call Supressiya. In certain cases insufficiency of a hematopoiesis is temporary and reversible - the main factors are the concentration/dose of substance and time of contact here. marrow supressiya.
- Viral infections. From virus agents the greatest value is given to causative agents of hepatitises B, C and D. In this case hypoplastic anemia usually develops within half a year after the postponed viral hepatitis. When studying pathogenesis it was noticed that replication of a virus happens in mononukleara of blood and marrow, and also in immune cages. It is supposed that suppression of a miyelopoez in this case is the peculiar immune answer arising against the cages bearing virus anti-genes on the surface. Such type of anemia is allocated in a separate form – postgepatitny. Among other viral infections TsMV, infectious , flu are called.
The cases pan-cytosinging caused by infection with tuberculosis, intoxication, radiation sickness, limfoproliferativny diseases (timomy, a lymphoma, a chronic limfoblastny leukosis), are also described by pregnancy. Almost in half of observations the reason of anemia does not manage to be revealed - such cases carry to an idiopathic form.
Either primary damage of haematopoietic stem cells, or violation of their effective differentiation can be the cornerstone of aplastic anemia. At hereditary anemias insufficiency of a hematopoiesis is mediated by the kariotipichesky aberrations leading to violation of a reparation of DNA and impossibility of replication of stem cells of marrow. In case of the acquired anemia under the influence of etiofaktor activation of T-cages which begin to produce the tsitokina (interferon - gamma, FNO) striking hematopoiesis cells predecessors is observed. In stem cells of marrow the expression of the genes which are responsible for apoptosis and activization of cellular death raises. The main clinical manifestations are caused by a pangemotsitopeniya – decrease as a part of blood of all its uniform elements (erythrocytes, leukocytes, platelets).
Except various etiologichesky options (medicinal, postgepatitny, idiopathic), distinguish sharp (up to 1 month of a current), subsharp (from 1 to 6 month) and chronic (more than 6 months) a disease form. The anemia proceeding with selective oppression of an eritropoez is called a partial krasnokletochny aplaziya. On the basis of expressiveness trombo-and granulotsitopeniya this form of anemia is subdivided into 3 severity:
- very heavy (platelets less than 20,0Õ109/l; granulocytes less than 0,2Õ109/l)
- heavy (platelets less than 20,0Õ109/l; granulocytes less than 0,5Õ109/l), according to a trepanobiopsiya – a low kletochnost of marrow (less than 30% of norm)
- moderated (platelets more than 20,0Õ109/l; granulocytes more than 0,5Õ109/l)
Symptoms of aplastic anemia
Defeat of three haemo poetic sprouts (eritro-, trombotsito-and a leykopoeza) causes development of anemichesky and hemorrhagic syndromes, infectious complications. The debut of aplastic anemia usually occurs sharply. The Anemichesky syndrome is followed by the general weakness and fatigue, pallor of skin and visible mucous, noise in ears, dizziness, a pricking in a breast, short wind at loading.
The hemorrhagic syndrome acts as the main display of thrombocytopenia. Patients note emergence of petekhiya and ekhimoz on skin, the raised bleeding of gums, spontaneous nasal bleedings, menorragiya. Emergence of a gematuriya, uterine and gastrointestinal bleedings is possible. As the investigation of a leykopeniya and agranulotsitoz serves frequent development of infectious processes – stomatitises, pneumonia, infections of skin and urinary tract. For aplastic anemias weight loss, a limfadenopatiya are uncharacteristic, gepato-and a splenomegaliya – at these signs it is necessary to look for other reason pan-haemo cytosinging.
Congenital aplastic anemia (Fankoni's syndrome) usually develops at children aged up to 10 years and except an aplaziya of marrow is characterized by other violations: mikrotsefaliya, hypoplasia of kidneys, low-tallness, anomalies of development of the top extremities (hypoplasia of the first pyastny and beam bone), gipospadiya, skin hyperpegmentation, extreme degree of relative deafness, etc. At hereditary anemia of Estrena-Dameshek total defeat of blood formation and pan-cytosinging in the absence of congenital anomalies of development is noted. Only decrease in quantity of erythrocytes is characteristic of Daymonda-Blekfen's anemia or a partial krasnokletochny aplaziya.
The lethal outcome can be caused by hemorrhages in internals, massive bleedings, infectious complications, an anemichesky coma. The most terrible of hemorrhagic complications – hemorrhage in a brain (a hemorrhagic stroke). Patients are inclined to the frequent and hard proceeding viral and bacterial infections of a respiratory path. Considerable or rapid decrease in level of red blood cells can lead to an anemichesky coma. At a lightning form the hardest anemia, an immunodeficiency, koagulopatiya having fatal consequences extremely quickly develop.
Assessment of the hematologic status includes attentive clinical examination and performing careful laboratory diagnostics. At fizikalny inspection the expressed pallor or yellowness of skin, arterial hypotonia, tachycardia comes to light. The basis of a diagnostic algorithm is made by performing the general and biochemical blood test, a sternalny puncture, trepanobiopsiya:
- Blood tests. At hypoplastic anemia are typical for a gemogramma eritro-, leykotsito-and thrombocytopenia, a neytropeniye and relative . Assessment of biochemical indicators (hepatic tests, a nephrological complex, serumal iron, bilirubin) is informative for an exception of other anemias.
- Research of a punktat of marrow. In a miyelogramma reduction of quantity of miyelokariotsit and megakariotsit, decrease in a kletochnost is found. In a trepanobioptata replacement of red marrow with fatty (yellow) is defined.
Within diagnostic search aplastic anemia needs to be differentiated with megablastny (B12-scarce, foliyevodefitsitny) anemias, an idiopathic trombotsitopenichesky purpury, paroksizmalny night gemoglobinuriya, a sharp leukosis.
Treatment of aplastic anemia
Patients with aplastic anemia are hospitalized in specialized offices. Full isolation and aseptic conditions for the prevention of possible infectious complications are provided to them. Performing effective treatment is a complex problem of practical hematology. Depending on level cytosinging the following medical approaches are used:
- Immunosupressiny therapy. At moderated cytosinging the pharmacotherapy including a combination of antitimotsitarny immunoglobulin and a tsiklosporin is appointed And. The supporting therapy is carried out by anabolic steroids or their combination to tsiklosporina.
- Hemotransfusions. In a complex with a course of immunosupressivny therapy at low indicators of red blood performing replacement haemo transfusion therapy (transfusion of platelets and eritrotsitarny weight), a plasma exchange is shown. This measure does not make impact on a pathogenetic link of a disease, but allows to fill shortage of the blood cells which are not developed by marrow.
- Transplantation of KM and SK. Optimum forecasts for long-term survival are rendered by performance of allogenny transplantation of marrow. However in view of complexity of selection immunological of the compatible donor the procedure is used restrictedly. As experimental approaches autologichny transplantations, change of stem cells of peripheral blood are considered. Carrying out a splenektomiya, endovascular occlusion of a splenic artery can be shown to patients with not severe form of anemia.
Forecast and prevention
The forecast is defined by an etiologichesky form, weight and sharpness of a course of anemia. As criteria of a failure serve bystry progressing of a disease, a heavy hemorrhagic syndrome and infectious complications. After transplantation of marrow of remission it is possible to reach at 75–90% of patients. Primary prevention of this kind of anemia assumes an exception of influence of adverse vneshnesredovy factors, unreasonable use of medicines, the prevention of infectious incidence, etc. Patients with already developed disease need dispensary observation of the hematologist, systematic inspection and the long supporting therapy.