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Hemolitic anemias - 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 ANEMIAS CONNECTED WITH THE RAISED KROVORAZRUSHENY
(HEMOLITIC ANEMIAS)

It is known that erythrocytes, having existed 100 — 120 days, perish. To replace the dead appear new, formed in marrow. This process which is continuously happening in an organism creates the dynamic equilibrium providing constant quantity of erythrocytes in blood in normal conditions. However there can be situations at which destruction of erythrocytes (hemolysis) happens more intensively, than their education and emission in peripheral blood. Such process leads to developing of hemolitic anemia. It should be noted that intensive destruction of erythrocytes can take place crises or be observed constantly in connection with reduction of their term of life activity.
In recent years knowledge of the reasons of hemolitic process considerably was replenished thanks to achievements of genetics, enzymology, studying of structure and structure of various systems of erythron. On the one hand, it gives the chance of a deep assessment of a being of the exchange disturbances in system of erythron conducting to the raised krovorazrusheniye. On the other hand, it to some extent complicates sozdaiy modern classifications of hemolitic anemia in connection with complexity of groups of various forms and consistencies of both a clinical, and biochemical orientation. Nevertheless one principle is recognized by most of hematologists — division of hemolitic processes on hereditary and acquired. Reduction of life expectancy of erythrocytes and premature hemolysis owing to their certain deficiency of the hereditary nature is characteristic of the first group of hemolitic anemias. At the acquired hemolitic anemias life expectancy of erythrocytes decreases under the influence of different factors.
The clinical picture of hemolitic anemias is very variable and depends on an etiology, a pathogeny of a disease, duration of its current, and also extent of compensation of hemolitic process. For confirmation of this or that specific form of hemolitic anemia use the following diagnostic methods: 1. Research of peripheral blood with calculation of reticulocytes and in certain cases — marrowy punctate. 2. Definition of fractions of bilirubin in blood serum and bilirubin products in Calais and urine. 3. Definition of free hemoglobin in blood serum and urine. 4. Calculation of erythrocytometric indicators (average diameter, volume, erythrocyte thickness, sphericity index). 5. Determination of osmotic and acid resistance of erythrocytes. 7. Statement of the test of an autogemoliz. 8. Research of fermental systems of erythrocytes. 9. Definition of types of hemoglobin. 10. Serological researches (direct test of Koombs, agregatgemagglyutinatsionny test, definition of cold agglutinins, definition of autohemolysins). 11. Determination of life expectancy of erythrocytes. 12. Analysis of family trees.

The hereditary hemolitic anemias connected with disturbance of a membrane of erythrocytes

Hereditary microspherocytosis (Minkowski's illness — Shoffara). This pathology is eurysynusic and clinically well studied. For the first time the disease is allocated in the second half of the 19th century, and then O. by Minkowsky (1900) and A. Chauffard (1907) is in detail described. It is inherited on autosomal dominantly type, but has variable degree of an expression therefore parents of sick children can be healthy. At the same time, in view of a dominant mode of inheritance the probability of developing of an illness at posterity is high (fig. 26). Sporadic cases are rather seldom noted. Prevalence of a hereditary spherocytosis makes 2 — 3 on 10 000 population.
It is established that life expectancy of erythrocytes at a microspherocytosis is many times less that than erythrocytes at healthy people. The reason of a qualitative change of erythrocytes is not clear. It is established that the increased destruction of erythrocytes in a spleen is connected with primary pathology of erythrocytes that was revealed at cross transfusion of marked erythrocytes from healthy the patient and vice versa. The spleen is the main body in which there is a destruction of defective erythrocytes.

Fig. 26. Family tree of a family of V. with an inborn spherocytosis
Генеалогическое дерево семьи с врожденным сфероцитозом

The most recognized is the theory according to which genetically caused defect of structure of protein of a membrane of an erythrocyte is the cornerstone of a microspherocytosis. It is proved that at an electrophoresis there is no one of fractions of structural protein of a membrane of an erythrocyte (M. V. Kamyshintsev and soavt., 1973; N of S. Jacob and soavt., 1970; A. Gompertz and soavt., 1973). Primary defect of a membrane puts a number of the interconnected pathogenetic mechanisms causing an increased hemolysis of erythrocytes in a spleen in action.

этапы патогенеза наследственного сфероцитоза
Fig. 27. The main stages of a pathogeny of a hereditary spherocytosis (according to N. of S. Ja cob, 1964, with additions Yu. R. Kovalyova and soavt.)

From these positions a pathogeny of a hereditary microspherocytosis consider as follows (fig. 27). Defect of a membrane of an erythrocyte promotes increase of its permeability for ions of sodium and water that causes swelling of a cell. Processes of glycolysis are in turn activated and intensity of a metabolism of phospholipids of a membrane increases. Unlike normal erythrocytes, sferotsita are less elastic that complicates their dekonfiguration at penetration through narrow openings of membranes of a pulp of a spleen. It results in stagnation of erythrocytes in a spleen where, as we know, conditions for their life activity adverse (concentration of cholesterol, glucose are reduced, pH is changed). Finally the part of a membrane of an erythrocyte when passing through narrow openings in a spleen is lost. After several circulations the erythrocyte perishes, being exposed to a lysis and phagocytosis.
Hemolitic anemia of Minkowski — Shoffara is clinically quite often shown already at early children's age. However more expressed
symptoms of a disease find by the end preschool and at the beginning of school age.
Clinically hemolitic anemia of Minkowski — Shoffara can proceed in two forms — easy and heavy. The central place in a clinical picture is taken by three cardinal signs: jaundice, pallor of skin and splenomegaly. At a heavy current a splenomegaly considerable, at a lung, subclinical — insignificant. A distinctive feature of jaundice is its akholurichnost, that is lack of bilious pigments in urine, but the urobilinuria is noted. Jaundice proceeds against an indirect hyperbilirubinemia. Pallor of skin is caused by existence of anemia and its intensity depends on anemia degree. Along with these symptoms the following changes of a bone skeleton are in certain cases observed: a tower skull, widely placed eyeballs, a wide nose bridge, the Gothic sky, disturbances of dentition. If clinical signs of a disease arose in the early childhood, the progressing anemia can lead to a growth inhibition, an intellectual underdevelopment, a hypogenitalism.
At Minkowski's illness — Shoffara anemia on character is constant: out of hemolitic crisis it is less expressed, in the period of crisis — is sharp.
The easy form is characterized to the constants which are moderately raised pallor of skin moderate. It is noted more or less expressed by hemolysis. The general satisfactory condition, activity it is kept, an ikterichnost or a subikterichnost of scleras and a mucous membrane of a hard palate. There are no changes of cardiovascular system. There can be a small increase in a liver and spleen, a thicket of the last.
The severe form of a disease proceeds with hemolitic crises, sometimes heavy. In these cases the disease is shown sharply and characterized by disturbances of the general state, sometimes moderate feverish reaction, suddenly arising pallor and icteric coloring of skin. Due to the bile pleyokhromiya quite often in right the hypochondrium arises the acute pain which is followed by increase and morbidity of a liver that can lead to wrong diagnosis of infectious hepatitis; the spleen is, as a rule, increased. Kal is intensively painted, color of urine also nasyshchenny usual.
In blood at an easy form moderate anemia, the raised reticulocytosis, increase of level of an indirect bilirubin are noted. A characteristic sign of a hereditary mikrosfsrotsitoz is change of osmotic resistance of erythrocytes. Normal indicators at children make for the minimum resistance (the beginning of hemolysis) — in 0,40 — 0,44% NaCl solution and for maximum (full hemolysis) — in 0,28 — 0,32% NaCl solution. Decrease in the minimum firmness of erythrocytes is typical for a disease, that is hemolysis begins in 0,6 — 0,65% NaCl solution. The maximum osmotic resistance can be even a little raised — in 0,3 — 0,25% NaCl solution. At diagnosis of different forms of hemolitic anemia it is necessary to remember that decrease in osmotic resistance of erythrocytes can be also observed at hereditary not spherocytic hemolitic anemias. At Minkowski's illness — Shoffara specific changes acid eritrogramm are described (A. I. Vorobyov, M. D. Brilliant, 1964).
At morphological studying of red blood reveal characteristic changes: reduction of average diameter of erythrocytes, increase in thickness of cells, as a result of it average volume considerably does not change, the index of sphericity is lowered to 2 and less (at norm 3,2 — 4). In the painted smears of a sferotsita have an appearance of the small cells which are intensively painted without the central enlightenment, characteristic of normal erythrocytes. The quantity of microspherocytes can fluctuate over a wide range — from 5 — 10% to absolute majority. There is a certain parallelism between quantity of microspherocytes and extent of hemolysis which the more intensively, than is more than defective cells.
At a severe form of an illness of Minkowski — Shoffara in the period of hemolitic crisis define anemia of heavy degree (1 — 1,5ò1012/l erythrocytes, 30 — 35 g/l of hemoglobin), the raised reticulocytosis which can sometimes exceed 50% emergence of normocytes in peripheral blood is possible. Level of an indirect bilirubin is considerably increased.
At acute hemolitic crises the erythrocytopoiesis is carried out on normoblastny type. The Leykoeritroblastichesky ratio is reduced (to 1:2, 1:3) due to increase in quantity of cells of a red row. At height of hemolitic crisis in punctate of marrow sharply expressed hyperplasia of a red sprout is noted.
Minkowski's illness — Shoffara can proceed decades, without influencing substantially a state of health of the patient though hemolitic processes in the period of infectious diseases can be more intensive. The forecast in mild cases usually favorable, however in hard cases is serious as in the period of hemolitic crisis at untimely treatment there can come the lethal outcome.
At a hereditary microspherocytosis aregeneratorny crises are described. During such crisis marrow hypoplasia symptoms with selective defeat of an erythroidal sprout appear. Similar aregeneratorny conditions of marrow are short-term, 8 — 12 days and seldom more last, however they cause heavy anemia and can be a basic reason of sudden death. By data A. A. Mamatiyeva (1982), aregeneratorny crises can be the first clinical signs of an illness that considerably complicates statement of the correct diagnosis as more often during this period the acute leukosis is diagnosed. The clinical picture of aregeneratorny crises has a number of osochbennost: an insignificant ikterichnost at the expressed pallor of skin and mucous membranes, the moderate increase in a spleen which is not corresponding to weight of anemia, lack of reticulocytic reaction. Aregeneratorny crises are observed mainly at children at the age of 3 — 11 and, despite the weight, have reversible character.
Minkowski's illness — Shoffara can be complicated by formation of pigmental stones in a gall bladder and bilious channels. In this regard at patients symptoms of an angiokholstsistit, parenchymatous hepatitis with increase of level of direct bilirubin in blood are observed. Some researchers observed development of thrombosis of a splenic vein with the subsequent gastric bleedings and symptoms of a hypersplenism.
As it was noted, the hereditary spherocytosis can be shown at early age (neonatal and chest) that definitely complicates the correct diagnosis. As a rule, early emergence of symptoms of an illness testifies to weight of a current. Early emergence of intensive jaundice is characteristic. Along with moderate increase in a spleen the liver is quite often also increased. In blood the level of both indirect, and direct bilirubin is increased (the last to a lesser extent). Such clinical picture forces to carry out differential diagnosis with a hemolitic illness of newborns, parenchymatous hepatitis, mechanical jaundice. Data of the anamnesis, negative test of Koombs, change of erythrocytometric indicators, reduction of osmotic resistance of erythrocytes, a reticulocytosis have essential value for the correct diagnosis.
Treatment of a hereditary microspherocytosis is carried out depending on age of the child and expressiveness of clinical displays of a disease. In therapy it is possible to allocate two stages: the first — conservative treatment in the period of hemolitic crisis, the second — removal of a spleen. Pathogenetic therapy does not exist, however the splenectomy at most of patients leads to absolute clinical recovery though the available defect of erythrocytes remains. Therefore the splenectomy is the only radical method of treatment of a microspherocytosis. At rather favorable course of a disease the most optimum age for carrying out operation 4 — 6 years. However at heavy hemolitic process the age should not serve as restriction for carrying out a splenectomy in early terms. Absolute indications to operation are frequent hemolitic crises, the postponed aregeneratorny crisis, the continuous course of hemolitic process, development of cholelithiasis as complications of a hereditary microspherocytosis. At full compensation of hemolitic process it is possible to refrain from a splenectomy. The effect of a splenectomy is explained as follows: operation does not eliminate hereditary defect of erythrocytes, but at the same time the splenic filter is switched off and by that in a circulatory bed remains the least steady forms of erythrocytes — sferotsita thanks to what the erythrocytolysis in an organism sharply decreases (G. A. Alekseev, 1970).
Results of a splenectomy are visible in the first days: the quantity of erythrocytes and a hemoglobin content increases, pallor and yellowness of skin disappears, concentration of bilirubin is normalized. During the next postoperative period there is a hyperthrombocytosis which, however, is not followed by complications of trombotichesky character. By the end of the first month after operation there is a complete recovery of indicators of peripheral blood and there comes clinical recovery. The analysis of the remote supervision confirms good results of a splenectomy: children remain almost healthy, recurrence of a disease is not observed, exposure to intercurrent diseases usual. When performing a splenectomy it is necessary to remember that the large number of patients of this category can have spleniculus which preservation can lead further to recurrence of a disease. Therefore during operation it is necessary to examine carefully an abdominal cavity and, having found a spleniculus, to remove them.
Carry out the therapy directed to elimination of hemolitic crisis to the period preceding a splenectomy. The main directions it are elimination of bilirubinovy intoxication, correction of hemodynamic and metabolic disturbances. For this purpose use drop introductions of 10% of solution of glucose, a reopoliglyukin, Haemodesum, vitamins, alkalizing solutions. At heavy degree of anemia (hemoglobin less than 70 g/l) resort to hemotransfusions, preferably a packed red cells.
Now most of authors indicate inexpediency of use of corticosteroid hormones at a hereditary microspherocytosis in the period of hemolitic crisis. Also it is not necessary to resort to the drugs stimulating a haemo cytopoiesis. During remission of special therapy of a disease it is not required, except all-guarding actions.
Treatment of aregeneratorny crises has a number of basic features, first of all it is directed to stimulation of a haemo cytopoiesis and carrying out replacement hemotransfusionic therapy. For this purpose use corticosteroid hormones (1 — 2 mg/kg of weight a day), daily introduction of a packed red cells. Such therapy allows to bring the patient out of a serious condition. The postponed aregeneratorny crisis is the absolute indication to a splenectomy.
Patients with a hereditary microspherocytosis are subject to dispensary observation during the period both to, and after a splenectomy. Guarding actions include restriction of exercise stresses, refusal of preventive inoculations, sanitation of the centers of persistent infection. Carrying out courses of cholagogue therapy is recommended. At the bezretsidivny course of a disease children are struck off the dispensary register in 2 years.
At medicogenetic consultation it is necessary to consider that the risk degree of the birth of the sick child in the presence of anemia Minkowski — Shoffara at one of parents makes 50%.



 
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