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The hereditary hemolitic anemias connected with disturbance of structure or synthesis of hemoglobin - Practical hematology of children's age

Table of contents
Practical hematology of children's age
Embryonal hemopoiesis
Morfofunktsionalny characteristic of cells of marrow and peripheral blood
Marrow parenchyma cells
Peripheral blood of children of different age
The system of a hemostasis is normal
Etiology and pathogeny of leukoses
Acute leukoses
Acute leukoses - a preleukosis
Possibilities of a predictive assessment of a course of an acute lymphoblastoid leukosis at children
General principles of treatment of an acute leukosis
Chemotherapeutic drugs
Treatment of an acute lymphoblastoid leukosis
Treatment of myeloid forms of an acute leukosis
Infectious complications and symptomatic therapy of an acute leukosis
Consolidation and maintenance therapy of an acute leukosis
Immunotherapy
Remission and recurrence of an acute leukosis
Inborn leukosis
Neuroleukosis
Myelosis
Lymphogranulomatosis
Gematosarkoma
Macrofollicular lymphoma
Angioimmunoblastny lymphadenopathy
Leukemoid tests
Infectious lymphocytosis
Infectious mononucleosis
Leukemoid tests of different types
Dysfunctions of granulocytes
Leukopenias
Histiocytoses
Histiocytoses - an eosinophilic granuloma
Malignant histiocytosis
Family erythrophagocytal histiocytosis
Accumulation diseases
Nimann's illness — Peak
Angiopathies
Hemorrhagic vasculitis (Shenleyn's illness — Genokh)
Mayokki's purpura
Ataxy teleangiectasia
Entsefalotrigeminalny angiomatosis
Kortiko-meningealny diffusion angiomatosis
Cerebroretinal angiomatosis
Hypertrophic gemangiektaziya
Multiple and huge hemangiomas
Elastic fibrodisplaziya
Coagulopathies
Hereditary coagulopathies
Hemophilia And
Clinic of hemophilia
Treatment of hemophilia
Angiohemophilia
Cristmas disease (Kristmas's illness)
Hereditary deficit of factors of XI, XII, XIII and I
Dysfibrinogenemias
Hereditary deficit of factors of VII, X, V and II
Deficit K-vitaminozavisimykh of factors of coagulation
Syndrome of the disseminated intravascular coagulation
Clinic and diagnosis of the IDCS
Treatment of the IDCS
Thrombocytopenia
Idiopathic Werlhof's disease
Clinic and diagnosis of an idiopathic Werlhof's disease
Treatment of an idiopathic Werlhof's disease
Isoimmune Werlhof's disease
Transimmune Werlhof's disease of newborns
Trombogemolitichesky Werlhof's disease (syndrome Moshkovich)
Hereditary Werlhof's diseases
Trobotsitopatiya
Anemias
The anemias connected with blood loss
Chronic posthemorrhagic anemia
Iron deficiency anemias
Clinic and diagnosis of an iron deficiency anemia
Treatment of iron deficiency anemias
Sideroakhrestichesky, sideroblastny anemias
Megaloblastny anemias
Foliyevodefitsitny anemia
Hereditary forms of megaloblastny anemias
Hereditary dizeritropoetichesky anemias
The anemias connected with oppression of proliferation of cells of marrow
Hereditary hypoplastic anemias
Hemolitic anemias
Hemolitic anemias - an ovalocytosis, a hereditary stomatocytosis
Acanthocytosis, piknotsitoz
The hereditary hemolitic anemias connected with disturbance of activity of enzymes of erythrocytes
The hereditary hemolitic anemias connected with disturbance of structure or synthesis of hemoglobin
The acquired immune hemolitic anemias
Isoimmune hemolitic anemias
Treatment of a hemolitic illness of newborns
Autoimmune hemolitic anemias
List of references

The last decades are characterized by considerable achievements in studying of structure of proteinaceous part of hemoglobin and origins of a number of the symptom complexes connected with formation of abnormal pathological types of hemoglobin.
It is known that the proteinaceous part of hemoglobin of the adult — a globin — consists of two couples of polypeptide chains. The first couple — and - a chain — contains on 141 amino-acid rests, the second couple — the R-chain — after 146 amino acids of the remains.
Thus, 574 amino acids are a part of globinovy part of hemoglobin.
In a structure and - and P-chains is available much in common, their separate sites are similar concerning sequence of amino acids. Chains form eight semicircles designated by letters of the Latin alphabet from And to N.
Now about 50 options of hemoglobin differing on physical and chemical properties and amino-acid structure are known. From them three are normal, and the others pathological. HbP (primitive — primitive), HbF (fetal — a fruit), HbA belongs to so-called normal haemo globins (to adult — the adult). These are, in fact, ontogenetic phases of development of hemoglobin of the person.
HbP (primitive) — primary hemoglobin of a human embryo synthesized during the pre-natal period, generally during vitelline blood formation. It can be found in an embryo of 3-centimeter length, to 16 — the 18th week of pregnancy of HBR disappears. HBR hemoglobin which biological role still is up to the end not found out is in many respects similar to fetalis hemoglobin.
With 9 — 13-week age of a fruit the bulk of hemoglobin is provided to HbF (fetus), that is fetalis hemoglobin which is formed mainly during hepatic blood formation. Further, approximately with 18 — 20-week age, HbF HBA (adultus) which makes the main part of hemoglobin after the child's birth is replaced. It should be noted that at the newborn the maintenance of HbF in blood can reach 80%, but in the first 3 — 4 months of life almost all fetalis hemoglobin is replaced with HBA. HbF quantity (6 — 8%) is found sometimes in the child till 1st year of life.
According to modern representations, hemoglobinoses arise owing to mutations at the level of the structural or regulatory genes managing synthesis of polypeptide chains. The mutations which are caused in a structural locus the structure or sequence of an arrangement of amino acids in various peptides is broken. Due to replacement of this or that amino acid in this or that peptide of the R-polypeptide chain there are structurally abnormal haemo globins — C, D, E, etc.
Now the symptom complexes connected with existence normal, but characteristic of HbF fruit and also the diseases connected with HbS, HBS, HBE and HbD and with a combination of different pathological types of hemoglobin are rather in detail studied.
Hemoglobinopathies are widespread among the population of Africa, the coast of the Mediterranean Sea, the tropical Areas of Southeast Asia, and also among certain groups is the population Severnoy and Central America.
The fact that the hemoglobinoses in particular connected with pathological HbS it is equal as the hemolitic processes caused by deficit of G-6-FDG more often attracts attention meet in those areas where the tropical malaria caused by Plasmodium falciparum is eurysynusic. It turned out that such coincidence is not casual. In the course of evolution the molecule of hemoglobin and enzymatic systems of an erythrocyte adapted to intracellular (intra erythrocyte) parasitizing of a malarial plasmodium. It led to the fact that at so-called heterozygous individuals, that is the persons which obtained information from one of parents to synthesis of HbS, tropical malaria, as a rule, does not arise.
We pass to the description of separate clinical forms of hemoglobinopathies.

Thalassemia (inborn leptocytosis, targetoid and cellular anemia Sacks).

The disease is called a thalassemia as it was for the first time described at the population of coastal areas of the Mediterranean Sea (from Greek thalassa — the sea); the second two terms are connected with a peculiar form of erythrocytes. Cooley and Lee in 1925 is for the first time described. The continuous formation of HbF not inherent to an organism of the child is the cornerstone of process 1 years and to the adult are more senior. Besides, find a small amount (13 — 15%) of the A2 hemoglobin which is hemoglobin A option in patients.
The thalassemia is hereditary disturbance of formation of hemoglobin. It differs from other hemoglobinopathies in absence abnormal, that is changed on amino-acid structure, hemoglobin chains. Practically we face change only of a ratio of normal fractions of hemoglobin that depends on synthesis of its normal chains (the R-chain — at the R-thalassemia, and - chains — at and - thalassemias).
The main biochemical line of a big thalassemia is a significant amount of HbF — to 90%, and also increase in quantity of Hbag. The disease occurs generally at the persons who were born in the basin of the Mediterranean Sea and Southeast part of Asia. Besides, it is observed in America, the Central Europe, India, China. In the USSR cases are noted in Azerbaijan, Tajikistan, in the Moscow region, at natives of the Penza region.
Symptoms of hemolitic anemia can appear in the first days or weeks of life, but to a thicket arise in the first months of life or at the end of the 1st year. The first symptom of a disease — pallor. Skin is painted in lurid color, there is no expressed jaundice. Gradually the stomach in connection with significant increase in a spleen and less expressed increase in a liver increases. Symptoms of dystrophy accrue. Lag in physical development is noted. A peculiar outward of the child pays attention: parietal and occipital hillocks at disproportionately big head are increased, a nose bridge wide and sunk down, malars — fades cooley act.
At X-ray inspection in a bone tissue find the typical changes which are most sharply expressed in skull bones. Outside and internal tables of the scull are thinned, and the spongy layer is considerably expanded. It is connected with expansion of the space occupied by marrow as a result of a compensatory intensive miyelotsitopoez. Besides, in a bone tissue there are osteoporosis sites alternating with osteosclerosis sites. Bones of a skull can have an appearance of "hedgehog" or "brush" that is defined already in the second half of the 1st year of life of the child.
Changes in blood are characterized by the progressing hypochromia anemia, anizo-and a poikilocytosis, existence eritro-and normoblasts, a reticulocytosis. Limits of osmotic resistance of erythrocytes are expanded. The amount of serumal iron normal or is even increased. Changes in marrow are characterized by erythroblastic reaction with dominance of basphilic forms of erythroblasts and on vyshenny quantity of reticulocytes. With urine a lot of urobilin is emitted.
The following erythrocytes are typical: 1) the pale, reminding erythrocytes at a deep sideropenia — in connection with disturbance of a gemoglobinoobrazovaniye; 2) typical targetoid erythrocytes with concentration of a pigment in the center and on the periphery — Target cells. They very thin and therefore are called also leptocytes (leptocyt).
Except typical targetoid erythrocytes, the cells having communication between the central, saturated hemoglobin a site and a peripheral nimbus — so-called semi-targetoid cells meet. In a blood smear find also other abnormal erythrocytes.
Leukocytes and thrombocytes at a thalassemia are not changed. The leukopenia with a lymphocytosis is noted, and at hemolitic crises — a neutrophylic leukocytosis with shift to the left.
Characteristic data reveal at determination of osmotic firmness of erythrocytes. The minimum firmness is reduced at the expense of sferotsit, and maximum is increased at the expense of anulyarny and targetoid forms of erythrocytes. The disease gradually progresses without the periods of remissions and hematologic crises and comes to an end with death which occurs the earlier, than earlier there was anemia.
Thalaccemia minor arises at heterozygous carriers of a symptom of a disease when hereditary transfer of a gene happens from one of parents. It is the easy form of a disease which is characterized by generally erased hematologic signs, including existence of targetoid erythrocytes and sometimes unsharply expressed by increase of hemolysis without damage of internals. Clinically the illness can proceed asymptomatically.
Treatment depends on a thalassemia form. The small thalassemia does not demand active therapeutic intervention, at a big thalassemia repeated packed red cells transfusions, blood are necessary, it is necessary to enter vitamins parenterally. At a number of patients the effect of a splenectomy is noted.

Drepanocytic anemia

Drepanocytic anemia (S-hemoglobinopathy, drepanocytosis) belongs to diseases at which instead of normal HBA pathological HbS is synthesized; the last differs from HBA in the fact that in a P-chain of amino acids the molecule of glutaminic acid is substituted with a valine molecule. The changed electric mobility and the main thing — the changed electric charge of hemoglobin defining a possibility of a dekonfiguration, pasting and hemolysis of erythrocytes in the corresponding conditions is explained by it.
Drepanocytic anemia — one of widespread hemoglobinoses, mainly among Blacks, was described by J. Herrick in 1910. Specific property of blood at this disease is acceptance by erythrocytes of a crescent form in the conditions of decrease in partial pressure of oxygen in environment. Except the countries of tropical Africa, the crescent form of erythrocytes is widespread among residents of the basin of the Mediterranean Sea, especially in the Middle East, and also in some regions of India.
In domestic literature there are only single descriptions of this type of anemia (A. M. Akhundova, A.S. Tsirkin, 1962).
The disease arises only at homozygous carriers (HbSS), that is the persons which obtained information to synthesis of HbS both from the father, and from mother. Heterozygous carriers (HbAS) are almost healthy. However, in the conditions of a hypoxia they can have morbid conditions connected with the changed hemoglobin type, for example a spleen heart attack at rise on height in the unpackaged camera. In Africa, in particular in Ghana, the pathological haemo globins of a different look which are combined at the same person, for example HbSF, HbSD, HbASF, HbSC, etc. are eurysynusic. At such types of hemoglobin there is also a disease.
The disease has various symptomatology (R. L. Nagel, D. Fabry, 1985). SS hemoglobinosis (drepanocytic anemia) clinically proceeds as the progressing hemolitic process, sometimes with an intensive abdominal pain syndrome owing to a spleen heart attack. The last is caused by a blockage of vessels of a spleen crescent erythrocytes.
At the mixed SC hemoglobinosis most often the main complaint is the ostealgia and joints. Not casually this option of drepanocytic anemia received the name of "the African rheumatism". Sometimes there are aplastic or hemolitic crises. In blood define anemia of heavy or moderate degree of manifestation (1 — 3,5Õ1012/l erythrocytes). The color indicator meets standard. In usual smears crescent erythrocytes meet changeably. They are defined, previously having created conditions to a hypoxia.
Osmotic resistance of erythrocytes normal. SOE is also normal. The indirect bilirubin in blood serum is raised. The disease proceeds hard and often to 10-year age or earlier comes to an end letalno.
Symptomatic treatment.

Page hemoglobinopathy.

HBS differs from HBA in the fact that in the fourth peptide of the R-polypeptide chain the amino acid first one after another — glutaminic — is replaced with a lysine. The disease is widespread in the Western Africa with epicenter in the north of Ghana (Yu. N. Tokarev, 1967). Sporadic cases meet also in other places. As a rule, the hemoglobinosis clinically proceeds in the form of benign chronic hemolitic anemia with moderate jaundice and a splenomegaly, but without serious complications and effects. In some cases hemolitic or painful crises are possible. Allocate two options of painful crisis, abdominal (a spleen heart attack) and rhematoid. The disease does not influence the general development, growth of an organism and life expectancy. Changes of the device of a support and the movement are noted. The hemoglobinosis With can be combined with other pathological hemoglobinoses.



 
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