Thalassemia

Description:

Thalassemias represent heterogeneous group of a hemoglobinopathy which cornerstone decrease in synthesis of the polypeptide chains entering into structure of normal hemoglobin A is. The thalassemia is a mishenevidnokletochny anemia with the broken ratio of NYA and HbF on biochemical indicators; at the same time partial insufficiency of a certain chain or its total absence at dominance of other chain is possible. So, at disturbance of synthesis of ß chain will prevail and - chains and vice versa. The beta talassemia is caused by decrease in products of ß chains of hemoglobin. Unimpaired and - chains it is excessive collect in erythrogenesis cells that leads to damage of a membrane and destruction both cells of an erythroidal row in marrow, and erythrocytes in peripheral blood; the inefficient erythrogenesis and hemolysis with a hypochromia of erythrocytes because the hemoglobin content in erythrocytes is not enough develop. The first the American pediatricians Sacks and Li in 1925 described ß thalassemia. The severe ß thalassemia homozygous form received the name of a disease Sacks, or a big thalassemia. Besides, on expressiveness of anemia and other clinical symptoms allocate an intermediate, small and minimum thalassemia. In addition to the countries of the Mediterranean the thalassemia occurs in France, Yugoslavia, Switzerland, England, Poland, and also at residents of Transcaucasia and Central Asia where in some regions the frequency of a carriage reaches 10-27%.

Thalassemia symptoms:

The clinic of a big thalassemia is shown already in the childhood. Sick children have a peculiar tower skull, the Mongoloid person with the increased upper jaw. A precursory symptom of a disease Sacks - spleno-and a hepatomegalia, developing due to extramedullary blood formation and a hemosiderosis. Over time they create cirrhosis, a diabetes mellitus as a result of pancreas fibrosis, and the hemosiderosis of a myocardium leads to congestive heart failure. The homozygous beta talassemia  (a big thalassemia, anemia Sacks) is characterized by sharp decrease in formation of HbA1, significant increase in maintenance of HbF, the low, normal or increased maintenance of HbA2. The maintenance of NBF can fluctuate from 30 to 90%, sometimes there are lower than 10%. The course of a disease is characterized by the heavy hemolitic anemia which is shown by the end of the first year of life of the child, gepato-and a splenomegaly, a mongoloidiost of the face and a tower skull, lag of the child in physical development frequent yellowness and pallor of integuments. At a part of patients ulcers in shins develop. Radiological find a symptom of "hedgehog" or "brush" which is positive at increase in maintenance of HbF, it is negative at increase in percent of HbA2. At children aged from 6 months till 1 year in ossicles of feet and brushes thinning of a bast layer with swelling of a bone and formation of grubosetchaty structure of marrow comes to light. Since 1st year of life of the child the disturbance of development of bones which is quickly progressing till the puberty period is noted. It is long the continuing hemolysis (a reticulocytosis, increase in free fraction of bilirubin of blood serum, an urobilinuria, a hyper sideremia), frequent transfusions of eritrotsitny weight lead to development of a hemosiderosis of a liver and spleen. Quite often there is a formation of bilirubinovy stones in bilious ways. Level of hemoglobin reaches 30-50 g/l, a color indicator 0> 5 and below. In blood smears find the targetoid erythrocytes differing in a small hemoglobin content and shortening of life expectancy, анизопойкилоцитоз, eritro-and normoblasts. Increase in osmotic firmness of erythrocytes, a leukopenia is noted (in the period of hemolitic crisis). In marrow - irritation of an erythro-normoblastic sprout. Sometimes there are aplastic crisis or the phenomena of a hypersplenism. At a heavy homozygous thalassemia patients die on the first year of life, at rather quieter form of a disease they can live up to adult age. The heterozygous beta talassemia proceeds in a type of both asymptomatic, and manifest forms with slightly increased spleen, specific bone changes quite often expressed by hypochromia anemia frequent an anisocytosis, a poikilocytosis and the mishenevidnost of erythrocytes raised by their osmotic resistance increase in quantity of HbA2 (approximately to 8% of the general hemoglobin), at a part of patients - HbF (to 5%). At a heterozygous delta beta talassemia (F) the high content of HbF at the normal HbA2 level is noted. Clinical signs and hematologic shifts are similar meeting at a heterozygous beta talassemia. Homozygous forms of a delta beta talassemia (F) are shown by almost same kliniko-hematologic disturbances, as a homozygous beta talassemia. Only HbF is found in patients with this form of a disease. It is possible to distinguish persons from patients with a thalassemia with hetero-and the homozygous A2F-thalassemias forms which on the signs characterizing their current in essence differ from a beta talassemia a little. In group of patients with a beta talassemia cases of a big thalassemia meet the expressed clinical manifestations less than intermediate and small forms. At inspection of relatives of patients the minimum form of a beta talassemia is found more often. Allocate the following forms and - thalassemias: a fruit edema with Bart's hemoglobin (u4). hemoglobinopathy of N (beta4), and - a thalassemia-1 and and - a thalassemia-2. An edema of a fruit represents a homozygous state (on genes and - th-l), incompatible with life. Pregnancy in similar cases involuntarily is interrupted and at a fruit reveal a brain edema, a hepatomegalia. An electrophoretic research of hemoglobin Hb Bart's is found (80-90%, NBN which is combined with traces. The hemoglobinopathy of N - one of options and - thalassemias - is shown by hemolitic anemia, increase in a spleen, the heavy course of bone changes. The picture of peripheral blood is characterized by decrease in a hemoglobin content, anizo-and a poikilocytosis, a hypochromia and multiple inclusions in erythrocytes (the hemoglobin N which dropped out in a deposit). Heterozygous forms and - thalassemias come to light at N.' a-Talassemiya-1 (a small form of a disease) sick with a hemoglobinopathy relatives arises at a combination of a gene and - th-l with a normal gene of a-tsepochkovogo of synthesis. It is characterized by small anemia, moderated anizo-and a poikilocytosis, intra erythrocyte inclusions, the increased osmotic resistance of erythrocytes. At adult patients and - a thalassemia-1 gemoglobinovy fractions happen within norm, at newborns Hb Bart's (5-10%) comes to light. a-Talassemiya-2 (the minimum form of a disease) develops at a-th-2 gene combination to a normal gene and-tsepochkovogo synthesis. Clinical manifestations are absent.

Thalassemia reasons:

At a thalassemia synthesis of one of four chains of a globin is broken. Inheritance of pathology from one (heterozygosity) or both parents (homozygosity), type of the broken chain define expressiveness of clinical manifestations. The reasons for the increased death of erythrocytes are connected with the broken structure of a cell because of the wrong ratio of chains of a globin in hemoglobin. Except shortening of life of erythrocytes at this disease there is a death of cells of predecessors of erythrocytes in marrow.

Treatment of the Thalassemia:

Transfusions of erythrocytes.  At severe forms of a thalassemia the need for transfusions of erythrocyte blood preparations arises from first months of life and remains, though in different degree, for life – so-called transfusion dependence develops. It means that hemoglobin in blood of patients constantly continues to decrease also other real ways of its increase, except such transfusions, no. It is desirable that in the patient's blood the hemoglobin content did not fall to low figures, it is better to carry out repeated transfusion at even its satisfactory levels - 95-100ú/l. The matter is that at the expressed decrease in hemoglobin many become more active thalassemias inherent exactly pathological processes: for example, the mentioned excess pathological osteogenesis, increase in the sizes of a liver and spleen; function of all bodies worsens, resilience to infections because of the amplified air hunger decreases. At a big b-thalassemia except substitution of a lack of erythrocytes of the circulating blood channel by means of transfusions of erythrocyte components of blood are reached suppression of own excess, but ineffective krovoobrazovaniye in marrow of the patient, and also absorption of iron in intestines decreases. Thus, in observation of the patient with a thalassemia prevention of development of episodes of the expressed falling of level of hemoglobin is important – it, first, can directly threaten life, and secondly, promotes progressing of pathological manifestations of a thalassemia. At the same time transfusion of erythrocyte blood preparations has the essential minuses. It is known that at transfusions of blood preparations compatibility of the donor and recipient on a blood group, a Rhesus factor is surely considered. But as does not exist in the nature of genetically identical people, at repeated transfusions the patient's organism sooner or later begins to produce the proteins antibody reacting with other, more difficult parts of membranes of the poured blood cells (erythrocytes). Therefore after a while (usually 3-4 years) the organism of the patient becomes biologically "compatible" not with any donor suitable on a blood group and a Rhesus factor but only with the certain donors possessing a specific set of proteins-antigens on erythrocytes any more. Therefore it is desirable to carry out transfusions of erythrocyte environments at a thalassemia on the individual selection which is carried out by special isoserological laboratory of blood transfusion stations. Besides, erythrocyte environments for patients with a thalassemia have to be specially cleared of other biological components which are contained in blood (leukocytes, numerous proteins of plasma) as they are the reason of the so-called "pyrogenic" reactions which are shown oznoba and temperature increase is frequent to high figures. The whole blood is not transfused now, transfusions of the eritrotsitny weight raw by additional methods are also not desirable. As high cleaning erythrocyte environments the defrozen, washed or filtered erythrocytes which cause reactions much less often are now used. But anyway, with transfusion dependence of transfusion are inevitable therefore it is only possible to take measures to reduction of their side effects and the prevention of reactions and complications. At easier forms of a thalassemia when patients or have an anemia of easy degree (at the level 90-110gl), or hemoglobin is normal, and, above all – that it steadily remains at the patient eventually and does not continue to decrease steadily, transfusions of blood preparations are not carried out. Desferal. An important part of treatment is removal of excess of iron from an organism by means of drugs from group of "chelates" (so-called "chelate therapy") performed by the drug "desferal". Now treatment is accepted subcutaneous hours-long injections, use of special devices - so-called помп which are attached to clothes is the most convenient. From the syringe fixed in a pomp desferal in several hours gradually is entered subcutaneously to the patient. Ideally patients with a severe form of a thalassemia have to receive desferal throughout all life for 5 days a week, but in real life it is still hard-hitting. In the countries with big prevalence of a thalassemia, especially advanced (for example, in Italy) there are special state programs of the help to patients with a thalassemia which provide, except other treatment, providing with desferal and pompa, necessary for them, for its introductions. From the countries of the former USSR the similar program exists in Azerbaijan. It is necessary to store desferal in the dark place at +8-15C, to part just before the beginning of introduction. With care treatment by desferal at children is appointed is younger than 2 years in view of rather bigger risk of development of side effects of treatment. At such children treatment with desferal is begun if about 15-20 transfusions of blood preparations, i.e. the need for transfusions already quite big are carried already out. Desferal infusion is preferable to improvement of quality of life of patients at night. It is necessary to change systematically places of subcutaneous injections in avoidance of local injury of skin and subjects of soft tissues. As well as any treatment, therapy by desferal has the possible side effects. Allergic reactions to drug meet more often, also feverish reaction is possible. In case of emergence against the background of treatment by desferal of any new complaints it is necessary to see a doctor, it will resolve an issue of continuation of treatment and of how to treat side effects of desferal. Removal of a spleen (splenectomy) At some patients very big sizes of a spleen in itself begin to affect a condition of hemoglobin and other indicators of system of blood negatively. In such cases carry out its surgical removal. This operation does not cure of the thalassemia, though can soften its manifestations (that, however, can not occur). The splenectomy is carried out only at very big sizes of a spleen and also when strong indications of its pathological action on other indicators of blood (so-called "hypersplenism") take place, Operation is not reasonable before achievement of age of 5 years, the age of 8-10 years is considered optimum. The first year is usually observed good effect, but then recuring of manifestations of a thalassemia is possible, increase in a liver can accrue. Besides, the infectious risk, especially concerning accession of a so-called "pneumococcal" infection in the form of sepsis, pneumonia increases. In this regard the vaccination against a pneumococcus which is carried out preferably to the preoperative period is obligatory. In general the decision of a question of removal of a spleen always has to be made carefully. Change (transplantation) of marrow gains ground treatment of a thalassemia by means of bone marrow transplantation Now. It is the only method of radical treatment of a thalassemia. At identification of a thalassemia it is desirable that patients and members of their families "were typed on the HLA system" (i.e. underwent quite difficult biological inspection on compatibility) for the purpose of search of the possible donor of marrow. However to find the suitable donor usually difficult, the procedure of search of the compatible unrelated donor remains expensive and long on time so far. Also bone marrow transplantation is very expensive. Close relatives, even if are compatible on HLA antigens, quite often have a thalassemia. Therefore rather few patients with a thalassemia become real candidates for treatment by bone marrow transplantation for the present. It should be noted that results of bone marrow transplantation in many respects depend on quality carried out to the patient before therapy. Better results of bone marrow transplantation at children. Though development and deployment of new methods of treatment of thalassemias, including bone marrow transplantation, continues, nevertheless for the vast majority of patients really possible are stated above "traditional" methods of treatment so far. Now also methods of treatment of a thalassemia by means of genetic engineering are developed. Patients with a thalassemia should keep to a diet (table No. 5). The drinks containing tannin are useful: tea, cocoa, and also nuts, soy – these products reduce iron absorption. Because of tendency to caries fluoric toothpastes, timely sanitation of an oral cavity are recommended. For improvement of function of a liver the doctor appoints drugs – so-called "gepatoprotektor". Lipoic acid, Vit E, drugs of type well-known "Essentiale" concerns to them. Improves removal of iron from an organism ascorbic acid (vitamin C) in a dose 50mg/days up to 10 years and 100mg/days at children 10 years are more senior. Also treatment is applied by group B vitamins, folic acid. Increase in a dose of vitamins is carried out at a stress, pregnancy. Courses of cholagogue herbs - mint, oats, corn stigmas, a barberry, and also tyubazh are appointed. Features of treatment of other forms of a thalassemia "Intermediate" thalassemia. Owing to softer current the disease does not demand constant transfusions - usually not more often than 1 time in 2-3ned – 2-3mes. At accession of intercurrent diseases, at operations - transfusions of erythrocyte environments at hemoglobin level are carried out lower than 70 g/l. As a rule, treatment by desferal is appointed, but it is more preferable after the special research of exchange of iron on the level of its content in blood and the response to one-time administration of desferal (the so-called "desferalovy test"). At the big sizes of a spleen with signs it is excessive the increased function the question of its operational removal the "Small" thalassemia is considered. Does not demand transfusions of erythrocytes. At anemia appoint folic acid, the solution of a question of treatment by desferal on the level of serumal iron or the desferalovy test is also possible. At severe forms of a thalassemia, especially with existence of transfusion dependence, to the patient disability is made out.