Anemia symptoms

Anemia ( anemia) - a decrease in blood total hemoglobin, the number of red blood cells and hematocrit. How to treat this disease with folk remedies.

The generally accepted classification of anemia does not exist. Anemia can be defined as a series of clinical conditions in which the hemoglobin concentration in the peripheral blood is less than 120 g / l, and the hematocrit value is less than 36%.In addition to these hematological parameters, the morphology of erythrocytes and the ability of the bone marrow to regenerate are of great importance in the diagnosis of anemia variants. Hypoxic syndrome is the main pathogenetic factor of this heterogeneous group of diseases.

According to the classification of M.P.Konchalovsky, subsequently modified by GA.Alekseev and I.A.Cashier, all anemia in etiology and pathogenesis are divided into three main groups:

The leuko-erythroblast ratio in the patient's myelograms creates an idea of ​​the functional state of the bone marrow in anemia. In norm it is equal to 1: 4;in anemia with a sufficient function of the bone marrow is reduced to 1: 1 or even to 2: 1-3: 1, with severe forms of anemia( pernicious anemia) can reach 8: 1.By the ability of the bone marrow to regenerate anemia can be regenerative( with a sufficient function of the bone marrow), hyporegenerative( lowering the regenerative capacity of the bone marrow) and aregenerative - with a sharp inhibition of the processes of erythropoiesis( hypo- and aplastic) anemia. The morphological criterion of the compensatory efforts of the bone marrow is the exit into the peripheral blood of patients with regenerative forms of erythrocytes, which include normoblasts, erythrocytes with remnants of nuclear substance( Jolly's body, Kabo rings) and reticulocytes. The indicator of the adequacy of the regenerative capacity of the bone marrow is reticulocytosis: RI above 2-3% - evidence of an adequate bone marrow response to anemia-induced tissue hypoxia, a smaller index indicates the suppression of erythropoiesis. When erythropoiesis defects in the peripheral blood of patients with anemia appear degenerative forms of erythrocytes, leading to changes in blood smears: anisocytosis, poikilocytosis and anisochromia.

On the saturation of erythrocytes, hemoglobin anemia can be:

Depending on the diameter of red blood cells, anemia can be:

The anemia identified by these laboratory parameters is classified into:

In addition to the nature of the course, anemia is given:

In mild cases of anemia, clinical symptoms may be absent;compensatory mechanisms( strengthening erythropoiesis, activation of the functions of the cardiovascular and respiratory systems) satisfy the physiological need of tissues in oxygen. Severe anemia is accompanied by weakness, dizziness, noise in the ears, "flickering flies" before the eyes, increased fatigue, irritation. In this case, amenorrhea, gastrointestinal disorders and jaundice can be observed. The laboratory examination quantifies the severity of anemia and helps to establish its cause. Neglect laboratory tests of the patient even with mild anemia.the symptoms of the disease only indicate a latent disorder and give too little information about the origin and clinical severity of anemia.

Hemolytic anemia develops when circulating red blood cells are destroyed prematurely. Often, the bone marrow can not produce red blood cells quickly enough to compensate for their rapid destruction( even though the bone marrow can increase the rate of their production up to six times).The disease rarely threatens life, but it is difficult to cure.

Hypoplastic anemia develops when bone marrow stem cells are damaged and can not produce enough red blood cells, white blood cells and platelets. The disease can begin gradually or suddenly( acute form).Low content of red blood cells causes weakness, fatigue, pallor and dyspnea. The lack of white blood cells makes a person vulnerable to infectious diseases, and the lack of platelets increases the risk of bleeding. Therefore, hypoplastic anemia is potentially life threatening. In fact, in the absence of treatment, more than 80% of patients die in a year. This relatively rare disease is more common in men.

Inadequate or defective synthesis of heme and globins, disrupting erythropoiesis, is the reason for the appearance in the peripheral blood of the hypochromic and microcytic population of erythrocytes. Along with this, the shape of erythrocytes changes, due to the interaction of the structural components of the membrane with hemoglobin. Differential diagnosis of anemia included in this group - iron deficiency anemia( iron deficiency as a result of tissue tissue deficiency), atransferrinemia( iron transport disorders), anemia in chronic somatic diseases( disruption of iron utilization and reutilization) and thalassemia( hereditary defect in the synthesis of polypeptide chains of globins)primarily based on laboratory data.

Iron deficiency anemia develops when the usual iron stores in the body are so depleted that the bone marrow can not produce enough hemoglobin, a protein found in red blood cells containing iron and carrying oxygen in the blood stream. The most common cause of anemia is iron deficiency;this disease is rarely strong and usually is easily treated. In the case of a weak chronic form, symptoms are almost absent and can only be detected if the doctor has the results of a clinical blood test. More severe anemia leads to noticeable fatigue and other symptoms.

Iron deficiency anemia( IDA) - the most common form of anemia, is 70-80% of all anemic patients. Women suffer much more often than men: 7-11% versus 0.5-1.5%.Women report a high percentage( 20-25%) of latent iron deficiency. Loss of 15-30 ml of blood during menstruation leads to a loss of 7.5-15.0 mg of iron, whereas when absorbed, only 1-2 mg per day is absorbed into the body. Moreover, in the third trimester of pregnancy, iron deficiency is found in almost 90% of women and this deficit persists after giving birth and lactation in 55% of them. In parallel, iron deficiency anemia can develop in children due to inadequate iron production from a mother suffering from iron deficiency anemia, with prematurity, as well as the child's refusal to eat. The possibility of developing iron deficiency anemia in girls is higher. Most often in children 2-3 years, there is relative compensation, the hemoglobin content can become normal, but during puberty, iron deficiency develops again. According to L.L.Eremenko( 1994), the extreme habitat( short light day, low temperatures) of residents of the northern regions of Russia affects the indicators of red blood. Long stay in the northern regions contributes to a significant increase in the incidence of IDA.Deficiency of iron in a cold climate occurs twice as often as in the middle band of Russia.

An IDA is a group of polyethic hypochromic-microcytic anemias caused by a disturbance of bone marrow products of erythrocytes due to a decrease in the total amount of iron in the body and defects in heme synthesis. Anemia in the peripheral blood of patients is manifested by hypochromia, microcytosis, aniso- and poikilocytosis and a significant decrease in the content of hemoglobin in the erythrocyte: the number of erythrocytes within 4.8 x 1012 / l, hemoglobin 100 g / l, color index less than 0.6, MCY - 65 fl, MFN-24 pg, ICSU 290 g / l, serum iron reduced to 5 mmol / l, serum ferritin 25 μg / l, and saturation of transferrin with iron is only 16%.Regenerative changes in erythrocytes( exit to the peripheral blood of normoblasts and reticulocytes) are poorly expressed in IDA.

Anemias of this kind can develop as a result of chronic blood loss( bleeding from the gastrointestinal tract and rectum, menometrorrhagia, renal bleeding, etc.), idiopathic hemosiderosis of the lungs, increased need and reduced iron deposition( with accelerated cell growth, pregnancy,lactation, infection and intoxication).Deficiency of iron can be associated with increased need for it and often, especially in children and the elderly, is of nutritional nature or is caused by a reduction in iron absorption due to inflammatory processes along the gastrointestinal tract( upper small intestine), achlorhydria, gastrectomy. It is associated with a perverted appetite. The main risk factors for the development of IDA in young children can be smoking mothers and toxicosis of the first half of pregnancy. All these reasons, however, are not comparable in the frequency of anemia with blood loss.

The disease develops slowly, a gradual decrease in hemoglobin level contributes to adaptation to apoxemia, resulting in clinical symptoms late when anemia becomes very deep( hemoglobin is reduced to 50-30 g / l.) The clinical picture is diverse and is caused by both anemic hypoxia andtissue deficiency of iron. Usually, patients complain of general weakness, sometimes quite severe, despite mild anemia, frequent dizziness, sometimes headache, "flashing of flies" before the eyes, in a number of cases, fainting and shortness of breath with little physical exertion. There are pains in the chest, swelling. They observe an extension of the cardiac dullness to the left, anemic systolic murmur at the apex and pulmonary artery, "whinch noise" on the jugular vein, tachycardia and hypotension. The ECG shows changes that indicate a phase of repolarization. In elderly patients, severe iron deficiency anemia can cause cardiovascular insufficiency. In addition, the patients develop muscle weakness( manifestation of tissue sideropenia), which is not observed in other types of anemia. Atrophic changes occur in the mucosa of the digestive tract, respiratory organs, genital organs. In patients, hair is cut and dropped, nails become brittle, longitudinal and transverse striation appears, sometimes the concavity of the nails to the point of a spoon-like shape( coilonichia).In 25% of cases, changes in the oral cavity are observed. Taste decreases, tingling, burning and a feeling of bursting in the tongue. At the examination, atrophic changes in the mucous membrane of the tongue are detected, sometimes cracks are on the tip and at the edges, in more severe cases red spots of irregular shape( "geographical language") and aphthous changes. Atrophic process also captures the mucous membrane of the lips. There are cracks in the lips and jaws in the corners of the mouth( cheilosis), changes in tooth enamel. Characterized by the syndrome of sideropenic dysphagia( Plummer-Vinson syndrome), manifested by difficulty in swallowing dry and dense food, feeling of perspiration and sensation of the presence of a foreign body in the pharynx. Some patients in connection with these manifestations take only liquid food. There are signs of a change in the function of the stomach: eructation, a feeling of heaviness in the stomach after eating, nausea. They are due to the presence of atrophic gastritis and achilles, which are determined by morphological( gastrobiopsy mucous) and functional( gastric secretion) studies. Attention is drawn to the perversion of taste( pica chlorotica) - a craving for chalk, coal, tooth powder. Patients eat clay, earth, dough, ice. They are attracted by unpleasant smells of dampness, gasoline, acetone, kerosene, naphthalene, acetone, paints, etc. The defeat of the mucosa of the digestive tract is so typical of iron deficiency states that there was a misconception about its primacy in the pathogenesis of iron deficiency anemia. However, the disease develops due to sideropenia, and only then progresses to the development of atrophic forms. Signs of tissue sideropenia quickly disappear after taking iron preparations. Iron deficiency anemia has a chronic course with periodic exacerbations and remissions. As a rule, there is a slight flow or course of moderate severity;a severe degree of anemia is less common. A slight and moderate degree of iron deficiency anemia is characterized by reduced erythrocyte, serum ferritin and tissue iron pool with a constant transport fund. In the absence of proper pathogenetic therapy, remissions are incomplete and are accompanied by a permanent tissue deficit of iron.

The usual intake of iron into the body hardly compensates for the current need for it. Therefore, unforeseen loss of iron in chronic bleeding or with heavy menstruation easily lead to its deficiency. The depletion of iron stores begins without clinical manifestations, it is possible to reveal the hidden deficiency only by special studies, including determining the amount of hemosiderin in the macrophages of the bone marrow and the absorption of radioactive iron in the gastrointestinal tract. In its development, the VLD is divided into 2 stages:

Initially, the serum iron level and hemoglobin concentration in erythrocytes remain normal, and only the serum ferritin content decreases below 25 μg / l. The amount of transferrin, as well as the value of the total iron binding capacity of the serum, is increased. Then, depleted iron stores( iron level below 5 μmol / L and transferrin saturation below 16%) no longer provide effective erythropoiesis( Hb below 109 g / L, and erythrocyte ferritin content decreases).

Thus, the pathogenetic nature of iron deficiency is the expressed depletion of its organ and transport stocks, which leads to depletion of cells and tissues with iron-containing and iron-dependent enzymes, to disturbance of redox processes and metabolism in erythrocytes, to tissue hypoxia, to activation of peroxidation anddecrease in antioxidant activity. This is especially pronounced in IDA, which is the extreme degree of GI in the body.

The diagnosis of IDA consists of clinical manifestations, the presence of a cause for the development of JJ, laboratory data in the study of ferrokinetics and general analysis of peripheral blood. Currently, for the purpose of more accurate diagnosis, monitoring of such parameters of erythrocytes as MCV, MCH, ICSU and RDW, obtained on hematological counters, is carried out. In blood smears, small hypochromic erythrocytes, annulocytes( erythrocytes with no hemoglobin in the center, in the form of rings) predominate, red blood cells of unequal size and shape( anisocytosis, poikilocytosis).In severe anemia, individual erythroblasts may appear. The amount of reticulocytes is not changed and only increases with anemia that develops against the background of blood loss, which is an important sign of bleeding. Osmotic resistance of red blood cells is little changed or slightly increased. The number of leukocytes has a not very pronounced tendency to decrease. The leukocyte formula has changed little. Leukopoiesis is characterized by a slight increase in the number of immature granulocytes. The number of platelets usually remains normal;slightly increased with bleeding. In the bone marrow with iron deficiency anemia, an erythroblastic reaction with a delay in maturation and hemoglobinization of erythroblasts can be detected. The bone marrow is hyperplastic in most cases. The ratio of cells of white and red rows increases, the number of the latter predominates. Erythroblasts account for 40-60% of all cells, in many of them degenerative changes appear in the form of vacuolization of the cytoplasm, pycnosis of the nuclei, and there is no cytoplasm( bare nuclei).

Usually changes in iron metabolism are sufficient to diagnose a "latent iron deficiency", as presented by IDA, and if a lower level of b is detected( in women below 120.0 g / L and in men below 130.0 g / L)explicit JJ, or true IDA.However, anemia has a hypochromic character with a color index of less than 0.9 with the presence of aniso- and poikilocytosis, anisochromia and polychromasia of erythrocytes in peripheral blood.

Treatment of LVS, regardless of the degree of severity, must begin immediately after verification of the diagnosis and the establishment of the cause of JJ.

Table. Some oral iron preparations

Compensation for blood and tissue in the blood is possible with pharmaceuticals. Among them, there are currently more than 30 oral preparations and about 70 complex multivitamins that contain iron. Parenteral administration of iron preparations does not increase the effectiveness of treatment and is indicated only with severe and extensive lesions of the gastric mucosa and small intestine, reducing the absorption of iron. For the correct choice of the drug, it is necessary to take into account the amount of trace element in each tablet or in a different dosage form. The daily dose should be 180 grams of salt or at least 100 mg of pure iron. The most physiological are preparations containing not tri-and bivalent iron, which is well absorbed in the stomach and in the small intestine, especially when the level of hydrochloric acid decreases( the latter is characteristic of chronic IDA).The drug should have a prolonged effect, which reduces the frequency of medication and is well tolerated by patients. The listed requirements, for example, are answered by the drug of the firm "Ranbaxy" - the drug "Fenyuls".It contains the optimal amount of bivalent iron - 45 mg, which makes it easy to dose the drug. In addition, Feniuls contains vitamins B1, B2, B5, B6, C and PP, which improves the absorption and assimilation of the trace element. The presence of a daily amount of vitamin B( 2 mg), improves the metabolism of myocardiocytes and their contractile function, which is necessary for anemic myocardial dystrophy, and the daily amount of vitamin B2( 2 mg) contributes to the correction of trophic disorders in the cells of the gastrointestinal tract and improves the activity of the stomach and intestines. Daily amounts of nicotinamide( 15 mg) and vitamin B2( 2.5 mg) normalize the redox processes and improve the intracellular metabolism disturbed in the JJ in various tissues and organs. The microdialysis granular form of the Fenyuls release ensures the gradual release of iron from the capsule, which excludes local irritation of the gastrointestinal mucosa, manifested by abdominal pain, nausea, eructation, stool disorder, unpleasant metallic taste in the mouth. The form of the Fenyuls release in the form of gelatin capsules prevents the formation of a dark border on the teeth, which often occurs with oral long-term intake of tablet forms of iron-containing preparations.

The duration of treatment( at least 1.5-2 months) is determined by the restoration of iron stores( serum ferritin), and not only normalization of the concentration of hemoglobin, serum iron, the number and morphology of erythrocytes. In infants with infectious complications, the duration of therapy with maltopeger, for example, in mild-to-severe IDA, is 7.8 weeks, and at an average of 9.1 weeks;At the end of the rehabilitation course of ferrotherapy the effectiveness of the drug reaches 100%.

The appointment of preventive courses of therapy with iron preparations( mainly in late autumn and early spring months) depends on the tendency of serum ferritin concentration to decrease, i.е.is performed in accordance with the results of control blood tests. For the purpose of preventing the development of iron deficiency in newborn children, ferrotherapy of pregnant women with gestational iron deficiency anemia is shown.

Blood transfusions during the usual course of IDA are not shown. Transfusions of erythrocyte mass may become necessary in refractory forms, when it is not possible to detect and eliminate the causes of resistance to iron preparations.

Similar therapeutic tactics relieve patients of severe relapses of anemia. According to various authors, approximately 1% to 3% of patients with IDA are refractory to ferrotherapy. The causes of refractoriness can be endocrinological disorders, in particular, dysfunction of the thyroid gland. The lack of effect can be associated with a deficiency of folic acid and vitamin B12.The presence of severe systemic diseases of connective tissue, cancer processes, chronic renal failure, a decrease in antioxidant activity or chronic infections reduce the effectiveness of the therapy. These conditions require identification with the full participation of relevant specialists and a combination of ferrotherapy with the elimination of the causes of refractoriness. In anemia associated with inflammatory processes, the restoration of ferrokinetics, erythropoietic factors and morpho-functional characteristics of erythrocytes correlates with recovery from an infectious disease.

Anemia associated with impaired iron transport( atransferrinemia) is a very rare form that occurs with defects in the transfer of iron from its depot in the cells of the liver, spleen, skeletal muscles, intestinal mucosa to the heme synthesis site, ie, to the bone marrow. Perhaps the cause of the disease is the lack of transferrin or its conformational changes.

Morphologically, this variant of anemia does not differ from iron deficiency. However, hemosiderin concentration significantly increases and hemosiderosis of lymphoid tissue is observed, especially along the gastrointestinal tract.

Anomalies in the incorporation of iron in the heme during its synthesis, leading to an increase in the content of trace elements in the mitochondria of cells, reduce the effectiveness of erythropoiesis in the bone marrow and lead to the development of refractory and sideroblastic( iron-saturated) anemia.

As the main clinical manifestation of all forms of myelodysplastic syndrome( MDS) that is heterogeneous in its composition, refractory anemia in 41% of patients is profound anemia( Hb <80.0 g / l) with recycylocytopenia, normo- or hypercellular bone marrow, with dyseritropoiesis phenomena. According to N.S.Turbine et al.(1985), morphological signs of dyseritropoiesis include: megaloblasticity of hematopoiesis, multinucleation of erythroblasts, dissociation of maturation of the nucleus and cytoplasm, basophilic cytoplasmic puncture, the presence of internuclear bridges, and annular forms of sideroblasts.

The processes of proliferation and differentiation of erythroid cells in the bone marrow of patients with refractory anemia in comparison with healthy people are reduced by 2.5 times: the partial label index of H3-thymidine is 12D ± 1.1% versus 30.0 ± 1.11%.

The levels of iron and ferritin, including acid isoferreretins, in the serum of patients significantly exceed the norm. Complementing the morphological signs of dyseritropoiesis and the results of the cytochemical reaction to polysaccharides, the biochemistry of serum confirms the enhancement of ineffective erythropoiesis already in the debut of MDS.Thus, increased iron saturation with these variants of anemia is combined with increased destruction of erythroid cells in the bone marrow.

Table. Metabolism of iron in patients with refractory anemia.

It is interesting that in hematopoietic depressions, the frequency of pathological red blood cells in the peripheral blood of patients is positively correlated with the frequency of SHIC-positive cells in the erythron. The percentage of SHIC-losative cells in the bone marrow of patients with sideroblastic anemia exceeds the norm sevenfold, i.е.ineffective erythropoiesis contributes significantly to the pathogenesis of this particular disease.

The picture of peripheral blood in patients with sideroblastic anemia is characterized by a variety of morphology of erythrocytes: microcytosis and macrocytosis, hypochromia and normochromia can be observed. Moreover, anisocytosis can be expressed more than hypochromia. The color index varies from 0.4 to 0.6.The hemoglobin content in the erythrocyte( MCH) is 30 pg, and the average hemoglobin concentration in erythrocytes( MSCH) is 340 g / l. The average volume of erythrocytes( MCV) also does not differ from the norm and is 104 fl. Polychromatophilic siderocytes( norm: 0,6 ± 0,04%) are more common than in the peripheral blood of patients, and hemosiderin deposits and increased content of sideroblasts including their ring-shaped forms( 15%) are revealed in the smears of the bone marrow. These cells are detected using a reaction with Berlin azure, based on the formation of ferri-ferrocyanide upon the interaction of ferric ions with ferrocyanide in an acidic medium. The reaction manifests itself in the form of a blue or green precipitate of ferri-ferrocyanide.

In addition to quantitative changes in the composition of peripheral blood cells, there is a pronounced biochemical shift. Thus, serum iron increases to 31 mmol / l and along with it serum and erythrocyte ferritin levels increase.

As a rule, palliative agents are used to treat anemia associated with impaired iron utilization. With deep anemia and the development of hypoxia, transfusions of the erythrocyte mass are required. However, such treatment increases the already existing excess of iron and accelerates the appearance of symptoms of hemosiderosis. More successful was treatment with desferal in combination with plasmapheresis, which contributes to a decrease in the number of blood transfusions and a decrease in hyper-glucose. Joining the main disease of infectious complications( bacterial pneumonia, tuberculosis, acute bronchitis, etc.) aggravates the course of anemia. And although the prognostic criterion is only the erythrocyte ferritin index( from 11 to 80 mg Hb), patients have an increase in serum ferritin and an increase in tissue iron stores. In this case, the effectiveness of anemia therapy depends on the successful treatment of complications.

Anemias in chronic diseases associated with a violation of the reutilization of iron, according to the frequency of occurrence, take second place. They are considered one of the manifestations of chronic diseases and malignant tumors, although they are found in any infection or inflammatory process.

If we consider that about 24 mg of iron is provided when it is re-used after the death of old red blood cells, it becomes evident that the delay in the release of iron in the cells of the reticuloendothelial system in chronic diseases contributes to the development of anemia - iron is not sufficient for the synthesis of hemoglobin in new red blood cells. There is an internal deficiency of iron. Additionally, the secretion of erythropoietin by the kidneys and the hypoproliferative state of the bone marrow can be reduced. All this leads to reticulocytopenia and inability of the bone marrow to satisfy the body's request for erythrocytes by hyperplasia of the erythroid germ and, accordingly, to the development of hypochromic-microcytic anemia.

Symptomatic is determined by the underlying disease. At an early stage of the disease, red blood cells retain their normal size, but then micro-cells begin to predominate. RDW in the anemia of chronic diseases has no differential diagnostic value. The concentration of hemoglobin rarely drops below 80 g / l, usually decreases by 20% of the normal level, the proportion of microcites increases approximately. Significantly exceeding the depth of anemia, the serum erythropoietin concentration decreases( 3 μ U / l).The concentration of serum iron drops to 5 mmol / l, but the serum ferritin level is higher than normal, erythrocyte ferritin remains within the normal range( 5-45 μg / g Hb), and iron transferrin saturation is below 10%.

Effective is the therapy of the underlying disease. Hemotransfusions in anemia of chronic diseases are rarely required.

Erythropoiesis-stimulating drugs usually do not work. However, in some cases, erythropoietin, especially recombinant asymptoms on the part of the lungs and the cardiovascular system, improves the red blood counts.

B12- and folic acid deficiency anemia - a group of anemia similar in symptoms with macrocytic anemia and megaloblastic anemia( return to fetal hematopoiesis).

Megaloblastic erythropoiesis with impaired erythrocyte maturation is usually caused by endo- or exogenous deficiency of vitamin B12 and folic acid. It develops for various reasons, among which:

Deficiency of vitamin B12 and folic acid can be congenital and manifest in early childhood, for example, Immerslung-Gresbek disease. Among the acquired megaloblastic anemias are: In 1 2-deficiency anemia Addison-Birmer, combined with atrophic gastritis, a decrease or lack of secretion of gastromucoprotein - an internal factor of vitamin B or Castle factor( 1929);B12-megaloblastic anemia of pregnant women;anemia due to increased use of vitamin B12 and folate with sprue or after surgical removal of the stomach and part of the small intestine. It is also known that the need for folates increases with hemolytic anemia or psoriasis. Macrocytic anemia, as a consequence of a deficiency of vitamin B12 or folic acid, may accompany refractory anemia.

ND Khoroshko et al.(2002) conducted a study of the level of vitamin B12 and folate in 250 patients with various hematological diseases. As can be seen, with B12-dependent anemia, a sharp decrease in vitamin B is observed both in serum( 117 ± 22 pg / ml) and in erythrocytes( 13.9 ± 3.3 pg / er).The concentration of folate in the serum remains normal( 9.7 ± 2.6 ng / ml), and in erythrocytes - decreases( 2.0 ± 0.9 ng / er).Therapy restores the levels of vitamin B12 in the serum to 259 ± 98 pmol / l and in erythrocytes to 75 ± 31 pg / er.

In folate-dependent anemia, decreased folate values ​​are detected both in serum( 2.1 ± 0.8 ng / ml) and in vitro cells( 1.6 ± 0.44 ng / er).In this case, the vitamin B12 content in the serum is somewhat reduced( 260 ± 45 pg / ml), while in the erythrocytes it remains within the norm( 280.8 ± 76.1 pg / er).

For comparison, in patients with IDA, a significant increase in the level of vitamin B12 and folate both in serum( 775.5 ± 66.7 pmol / l and 13.3 ± 3.1 pkmol / l) and in erythrocytes( 499± 77.6 pg / er and 19.3 ± 2.5 pg / er).N.D.Horoshko et al.(2002) suggest that in conditions of iron deficiency( against a background of reduced production of erythroblasts due to lack of metal), the consumption of these vitamins decreases sharply, as a result of which they accumulate in the blood serum.

At the same time, in young children, IDA occurs with a high content of vitamin B12 in the serum( 1200 ± 65 pg / ml), but with folic acid deficiency( 9.4 ± 1.6 ng / ml).This fact is explained by the increased needs of children of this age in folates due to the growth and development of the organism, including the nervous system, but also the peculiarities of their dietary regimen.

It is characteristic that after the course of ferrotherapy and normalization of the parameters of iron metabolism, the concentration of vitamin B12 and folic acid and in serum( 276 ± 33.9 pg / ml and 9.2 ± 2.1 ng / ml), and in erythrocytes( 128± 29.0 pg / er and 10.5 ± 2.9 ng / er) decreased. In infants less than 3 years, the decrease in the level of vitamin B12( 198 ± 47 pg / ml) and folate( 8.3 ± 0.7 ng / ml) in the serum against the background of ferrocorrection was more pronounced. These results can be considered as the basis for the course of vitamin therapy( cyanocobalamin and folic acid) IDA simultaneously with the appointment of ferro-preparations.

The majority of patients with autoimmune hemolytic anemia( AIGA) had a relatively normal content of vitamin B12( 490 ± 187 pg / ml) and folate( 9.2 ± 1.9 pt / ml) both in serum and erythrocytes( 249 ± 56, 9 pg / er and 6.1 ± 2.0 ng / er).During the remission with normalization of the Hb level, the vitamin B12 drops sharply to 20 pg / ml, and folate to 2.5 ng / ml. These data support the assumption of intensive consumption of vitamin B and folate at the moment of arresting anemia and are a convincing argument for AIGA therapy with vitamin B12 and folates( see the corresponding section).Perhaps the revealed differences in the levels of vitamin B12 and folate at different stages of the hemolytic process are associated with significant fluctuations in the lifespan of erythrocytes. Thus, at the height of the hemolytic crisis, "young" red blood cells quickly leave the bone marrow and, having entered the circulation, are quickly eliminated. During remission, as the erythropoiesis normalizes, the bulk of the red cells of the peripheral blood are represented by their normal forms. It is known that when centrifuging in a density gradient, "young" erythrocytes constitute a light fraction, and "normal"( exposed to natural aging) is heavy. When determining the levels of vitamin B and folate in each of them, it was found out that in the heavy fraction they are, respectively, 23 ± 5.2 pg / er and 1.2 ± 0.04 ng / er, and in the light fraction - 286 ± 35,8 pg / er and 14 ± 5.1 ng / er. Thus, the age of red blood cells can largely determine the fluctuations in vitamin levels during different periods of hemolytic anemia.

Determination of the concentration of cobalamins and folates in MDS patients showed that in the blood serum, the values ​​of vitamin B12 and folate are within the physiological norm. While in erythrocytes in most patients( 60%), the level of vitamin B is increased( 63 5 ± 16o pg / er).In the case of refractory anemia, patients with a high degree of ineffective erythropoiesis also have higher levels of vitamins in the erythrocytes, but not in the serum. In chronic myelo-proliferative diseases( CVD), the content of vitamin B in both erythrocytes and serum is within the physiological norm. The level of folate in the serum in this category of patients is also normal, and in erythrocytes this figure is lower in 70% of patients( <4.2 ng / er).This is despite the fact that the stocks of folic acid in the red blood cells are so great that they should decrease last. Perhaps the contradiction is due to the use of drugs that affect the metabolism of folates, since folic acid is extremely sensitive to the effects of various chemical compounds.

The study of the concentration of vitamin B12 and folic acid is useful not only to clarify the nature of megaloblastic anemia, but also for differential diagnosis and evaluation of the effectiveness of ongoing therapy for a number of hematological diseases.

The role of vitamin B12 deficiency and folate in the pathogenesis of megaloblastic anemias is that the function of thymidine synthase is violated against its background and the synthesis of DNA is interrupted. Rapidly dividing cells undergo megaloblast changes, erythroid bone marrow hyperplasia and intramedullary hemolysis occur, LDH( lactate dehydrogenase) and indirect bilirubin levels in blood serum increase. Defects of DNA synthesis in general, hemopoiesis lead to hyper-segmentation of neutrophils. In parallel with the above, the megaloblastic process also captures other rapidly dividing tissues - atrophy of the gastrointestinal tract is observed.

Macrocytic( megaloblastic) hyperchromic anemia develops gradually, characterized by pallor of the skin with icteric tinge, dyspeptic symptoms, glossitis pattern with papillary tongue( "lacquered" tongue) or a combination of bright red areas of inflammation with a dirty yellow coating, swelling of the tongue, folding of mucous membranes("Geographical language").The liver and spleen can be moderately increased. There may be neurological symptoms: paresthesia, burning sensation in the extremities, violation of the reflexes of the lower extremities, uncertainty of the gait( manifestations of funicular myelosis with B12-avitaminosis).Diagnosis of the disease and management of patients - a complex multi-step process, including:

It is necessary to identify the morphological features of peripheral blood cells and use them in differential diagnosis of the disease.

In patients with a deficiency of vitamins in peripheral blood tests with deep anemia, a decrease in the number of erythrocytes( less than 1.0 x 1012 / L) prevails, but the level of hemoglobin is reduced to a lesser extent. The hematocrit falls to 0.04 l / l. Degenerative changes in erythrocytes in the form of anisochromia and hyperchromia( CP = 1,2-1,5), anisocytosis with pronounced macrocytosis, megalocytosis and poikilocytosis with a tendency to ovalocytosis are observed in the blood. The mean diameter of erythrocytes is increased to 8.2-9.5 microns, their average volume( MCV) ranges from 110 to 160 fl. There are regenerative changes of the pathological type: the body of Jolly and the Kebot ring in erythrocytes, normoblasts. Often observed thrombocytopenia, part of the platelets represented by large forms, and reticulocytopenia. The number of leukocytes is normal or decreased, predominantly the hypersegmented granulocytes and, rarely, the giant forms of neutrophils. The above morphological characteristics can help in the diagnosis of megaloblastic anemias.

Large red blood cells in peripheral blood can be classified into two categories according to their morphology:

The appearance of peripheral blood of hypersegmented neutrophils distinguishes megaloblastic anemia from myelodysplasia, which is characterized by hypo-segmentation of leukocyte nuclei and platelet morphology defects. The differential diagnostic value of MCV erythrocytes in megaloblastic anemias is unquestionable, but it should be remembered that this erythrocyte index can increase to 160 fl and in reticulocytosis.

All listed signs of megaloblastic anemia are complemented by biochemistry: in the serum - moderate bilirubinemia due to the free fraction of the pigment due to hemolysis of megaloblasts. The LDH level often reaches 1000.

It is necessary not only to determine serum and erythrocyte levels of vitamin B12 and folate, but since 39% of patients with megaloblastic anemia suffer from iron deficiency and ferrokinetics. If there is no possibility of quantitative determination of vitamin B12 and folates, a bone marrow puncture is performed prior to the appointment of the bone marrow, which reveals megaloblastic hematopoiesis, which is the morphological criterion of the diagnosis. In bone marrow preparations, megalocytes and megaloblasts, giant metamyelocytes and megakaryocytes of irregular shape are found.

Patients with severe megaloblastic anemia require immediate therapy. The schemes vary, but it is common to quickly eliminate the vitamin deficiency and create their depots in the tissues. Usually, in patients with B12-deficient anemia, the number of reticulocytes( bone marrow regenerative response) increases on the third day of therapy, and on the fifth day - the hematocrit is restored. A positive response to folate therapy in case of deficiency or alcoholism is possible in three weeks. Blood transfusion is almost not required. Treatment - substitution, i.e.administration of vitamin B and folic acid at therapeutic doses of 200 mcg / day and 0.005 x 3 / day, respectively( higher doses of vitamin B12 500 mcg or 1000 mcg are indicated only with funicular myelosis), continues until the anemia stops and all its clinical and cytomorphological manifestations are normalized. Then, especially with Addison-Birmer anemia, practically constant maintenance therapy with vitamin B12 200 μg once every 1-2 months is shown.

Pernicious anemia is a rare type of disease in which an insufficient number of red blood cells are observed due to a lack of vitamin B12( cobalamin), an important component for producing red blood cells.

In most cases, the disease does not develop because of a lack of vitamin in food, which can only be observed in vegetarians. Usually this disease develops when the body can not properly digest the vitamin. Malignant anemia develops gradually and can initially have symptoms of any kind of anemia: weakness, fatigue, pallor. In the absence of treatment, the disease can cause disorders of the gastrointestinal tract, cardiovascular system and, especially, the nervous system, since vitamin B12 is important for its normal functioning. As a result of treatment, the disease quickly resembles, although severe disorders in the nervous system remain. Pernicious anemia can develop at any age.

Folic acid is an important vitamin for the production of red blood cells. A deficiency of this vitamin can cause anemia. As a result of reducing the number of red blood cells, body tissues are deprived of the necessary oxygen supply, which leads to the appearance of classic symptoms of anemia. The disease is especially common in children and adolescents during rapid growth, in pregnant or lactating women, in the elderly, in smokers, in alcoholics, in those who are addicted to diets or suffering from intestinal diseases. It can be accompanied by iron deficiency anemia.

Blood loss is considered the leading factor in the development of hypovolemic shock, which is based on a decrease in the effectiveness of blood flow over a significant period of time. The main pathophysiological changes in blood loss are presented in the diagram.

Table

Transfusion scheme for replacement of blood loss( PG Bryusov, 1997)

The blood loss is classified according to the size, severity and speed of development of changes in the body of the victim. The American College of Surgeons has established 4 classes of bleeding, depending on the volume of blood loss and clinical symptoms. Class I - corresponds to a loss of 15% or less of the volume of circulating blood. At the same time, there are no clinical symptoms or there is tachycardia at rest, especially when standing. Orthostatic tachycardia is considered when the heart rate( heart rate) increases by no less than 20 beats per minute, when going from horizontal to vertical position. Class II - corresponds to a loss of 20% to 25% of BCC.The main clinical sign is orthostatic hypotension or lowering blood pressure( blood pressure) by at least 15 mm Hg when moving from a horizontal position to a vertical one. In the prone position the blood pressure is normal or slightly reduced. Diuresis is preserved. Class III - corresponds to a loss of 30% to 40% of BCC.It appears hypotension in the supine position, oliguria( less than 400 ml of urine is released per day).Class IV - loss of more than 40% BCC, collapse( extremely low blood pressure) and impaired consciousness to coma.

For the diagnosis of blood loss, it is of fundamental importance to determine the magnitude of the BCC deficit. The most accessible indicator in this respect is the "shock index" - the ratio of the pulse rate to the value of systolic blood pressure. In the norm it is equal to 0.54.With blood loss, the shock index increases.

Acute posthemorrhagic anemia( hemic hypoxia) - decrease in oxygen capacity of blood, after rapid loss of a significant volume of circulating blood( BCC) due to external or internal bleeding. It develops as a result of injuries, surgical interventions, bleeding of the stomach, intestinal, uterine, with the rupture of the fallopian tube in ectopic pregnancy, etc.

Acute blood loss in the domestic literature is classified by magnitude, severity and rate of development of changes in the body of the victim. The clinical picture of these anemias is characterized by hypovolemia and hypoxia, loss of a significant amount of iron( 500 mg and more with heavy bleeding).Symptoms of this pathology depend on the volume of lost blood:

Rapid momentary loss of 30% or more BCC without urgent resuscitation is fatal.

Acute posthemorrhagic anemia is quickly manifested by a deceptive increase in the number of erythrocytes, hemoglobin concentration and hematocrit value per unit volume of peripheral blood. Normochromic-normocytic anemia( the color index ranges from 0.85 to 1.5 and the mean diameter of the erythrocytes is 7.8 microns) occurs immediately after hemorrhage, Then, from a few hours to 1-2 days, when diluted into the blood streamcirculating blood, tissue fluid begins to flow, these indicators are reduced, respectively, the severity of blood loss. In the smears of peripheral blood, there may be phenomena of moderate aniso- and poikilocytosis of erythrocytes. The number of platelets per unit volume of blood is reduced because of hemodilution or because of their consumption during thrombus formation. The total number of leukocytes is reduced both in connection with hemodilution, and in connection with loss during bleeding. The resulting hypoxia causes an increase in the level of erythropoietin and on the 4th-5th day the erythron regeneration begins and reticulocytosis occurs, polychromasia and anisocytosis( microcytosis) increase. In the case of massive bleeding, certain normoblasts( regenerative anemia) are revealed in the peripheral blood. The color index falls below 0.85( red blood cell hypochromia) due to the fact that the rate of hemoglobin synthesis due to iron deficiency lags behind the rate of proliferation of erythron cells. Neutrophilic leukocytosis develops with a shift to the left. In the bone marrow at this time, signs of intensification of erythropoiesis are revealed: the number of erythroblasts, various forms of normoblasts, and reticulocytes( bone marrow compensation of blood loss) is increasing.

Based on these data, the clinical and laboratory picture of acute posthemorrhagic anemia is divided into three stages:

The management of acute post-hemorrhagic anemia occurs 6-8 weeks after the bleeding stops if intensive therapy is performed correctly. After 2-3 weeks, the value of the reticulocyte index is normalized, after 4-6 weeks - the number of red blood cells, and then the hemoglobin concentration together with the morphometric parameters of erythrocytes.

Chronic posthemorrhagic anemia - anemia, which arises from abundant single or minor, but long-repeated bleeding. A particular variant of iron deficiency anemia. The disease is associated with increasing iron deficiency in the body due to prolonged bleeding caused by rupture of the vessel walls( infiltration of tumor cells in them, venous stasis of blood, extramedullary hematopoiesis, ulcerative processes in the wall of the stomach, intestines, skin, subcutaneous tissue), endocrinopathy( dyshormonal amenorrhea) and hemostasis disorders( violation of its vascular, platelet, coagulation mechanisms in hemorrhagic diathesis).It leads to the depletion of iron stores in the body, a decrease in the regenerative capacity of the bone marrow.

Patients with weakness, rapid fatigue, pale skin and visible mucous membranes, ringing or tinnitus, dizziness, shortness of breath, palpitations even with minor physical exertion, so-called anemic noises heard over the heart and jugular vein. The blood picture is characterized by hypochromia, microcytosis, low color index( 0,6-0,4), morphological changes of erythrocytes( anisocytosis, poikilocytosis and polychromasia).The pale coloration of erythrocytes with a wider central unpainted part is most often observed-the erythrocyte hypochromia, which is due to the low saturation of the erythrocyte with hemoglobin, which is typical of common forms of anemia associated with iron deficiency( in pregnant anemia, tumors, sepsis and other severe infections, diseasesgastrointestinal tract, etc.).This hypochromia, as a rule, is combined with a decrease in the size of erythrocytes - microcytosis. It should be borne in mind that the erythrocyte hypochromy can be observed not.only with a decrease in the concentration of hemoglobin and the number of red blood cells in the blood, but also with normal quantitative indices. Regenerative changes in erythrocytes( normocytes - normoblasts, reticulocytes) in chronic posthemorrhagic anemia are poorly expressed.

Bone marrow of flat bones of normal appearance. In the bone marrow of the tubular bones, the phenomena of regeneration and transformation of the fatty bone marrow into red are observed to varying degrees. Often there are multiple foci of extraosternal hemopoiesis.

In connection with chronic blood loss there is a hypoxia of tissues and organs, which causes the development of fatty dystrophy of the myocardium( "tiger heart"), liver, kidneys, dystrophic changes in the cells of the brain. Multiple point hemorrhages appear in serous and mucous membranes, in internal organs.

The severity of the course of anemia can be mild( hemoglobin content from 110.0 g / l to 90.0 g / l), medium severity( hemoglobin content from 90.0 g / l to 70.0 g / l) and heavy( the hemoglobin content is below 70.0 g / l).The number of leukocytes and platelets is unstable.

Treatment includes the earliest detection and elimination of the cause of blood loss, as well as the replacement of iron deficiency and iron content in serum. In severe cases, transfusion of erythrocyte mass is shown under the control of hemoglobin saturation.

The inability of the erythrocyte mass to adequately increase in response to a query of tissues and cells associated with a relative or absolute deficiency of erythropoietin is manifested by normochromic-normocytic anemia. Hypoproliferative anemia often occurs in renal disease. Decreased production of erythropoietin leads to insufficient stimulation of the bone marrow in the development of hypoxia. As a result, reticulocytopenia occurs and, in proportion to the severity of the anemia, the reactivity of the bone marrow decreases.

The severity of anemia in chronic renal failure correlates with the excretory capacity of the kidneys. According to T.G.Sarychevoy( 2000), with the preserved functional capacity of the kidneys( chronic pyelonephritis), even in the absence of anemia, the erythron of the bone marrow undergoes characteristic changes: the proliferative activity of cells decreases( label indices with НЗ-thymidine 22.9 ± 1.02% vs. 32.4 ± 1,11% in donors), ineffective erythropoiesis( 8.1 ± 0.84% ​​of SHIK-positive erythroid cells against 5.6 ± 0.8% in healthy bone marrow) is increased, electrophoretic erythrocyte motility is reduced( from 0.823 ± 0.06 μm/ cm / in-1 / sec-1 to 0.896 ± 0.05 μm / cm / in-1 / sec-1 in various observations against 1,128 ± 0,018 μm / cm / in-1 / sec-1 in the norm).In chronic renal failure, a significant decrease in the proliferation of erythroid cells of the bone marrow, a violation of cell differentiation and the synthesis of nucleic acids, globins, the appearance of red blood cells in the peripheral blood with a low( below 5 pg) hemoglobin content, a reduction in the population of erythrocytes with a normal or increased saturation of Hb to 40% andfurther decrease in the electric charge of their surface. All of the above can be considered as links in the pathogenesis of nephrogenic anemia.

Other pathogenetic mechanisms may worsen the condition. With uremia, hemolysis begins, i.e. Reduces the lifetime of erythrocytes. Less common, but it is easier to recognize anemia, called microangiospasm. In children, this lesion can develop acutely in the form of a hemolytic-uremic syndrome with a fatal outcome.

Treatment of renal anemia involves treatment of the underlying disease.

Aplastic anemia( AA) - deep pancytopenia, insufficient bone marrow hematopoiesis and a predominance of fatty bone marrow over the hematopoietic. AA was first described by Paul Ehrlich in 1888 from a 21-year-old woman.

The term "aplastic anemia" was proposed by Chow-Ford in 1904 and now collectively denotes a heterogeneous group of diseases differing from one another in the etiological and pathogenetic mechanisms of development, but with similar signs and a definite picture of the peripheral blood and bone marrow. Among these diseases, congenital and acquired are isolated. An example of the former are constitutional anemia Fanconi, familial hypoplastic anemia

Estrena-Damesheka and congenital partial hypoplastic anemia of Josephs-Diamond-Blackfen. The latter can result from a number of exogenous factors, for example, physical( radiation energy), chemical( dyes, benzenes) or drug( chloroethylamines, antimetabolites, sulfonamides, some antibiotics).Infectious diseases include Botkin's disease, disseminated tuberculosis, syphilis, typhoid fever, toxoplasmosis, severe influenza, sepsis. In addition to these factors, immune mechanisms play a role in the development of hypo-, aplasia of hematopoiesis. Some qualitative and quantitative differences between hypo-and aplastic anemia do not contradict the assumption of the generality of these conditions on the basis of the violation of the functions of the stem cell.

In 1927, Fanconi described three brothers with aplastic anemia and multiple hereditary disorders. Later, various cases of Fanconi syndrome were reported with both apparent family pathology and single cases in a family with a large number of brothers and sisters. Fanconi anemia, a syndrome characterized by aplasia of the bone marrow, which occurs in children under 10 years old, is often familial and is combined with such disorders as dark skin pigmentation, kidney hypoplasia, absence or hypoplasia of the thumb, radius, microcephaly andsometimes mental or sexual underdevelopment, multiple chromosomal abnormalities. Boys are 2 times more likely than girls. Pancytopenia usually appears at the age of 5-7 years and older. Similar changes in the blood are also observed with family hypoplastic anemia of Estren-Dameshek, but there are no developmental defects. Congenital partial hypoplastic anemia of Josephs-Diamond-Blackfen is usually found in the first year of life. Disease often proceeds benignly. The clinical picture develops gradually: lethargy, pallor of the skin and mucous membranes, appetite decreases. The blood reduces the content of hemoglobin, the number of erythrocytes and reticulocytes with a normal number of leukocytes and platelets. The greatest hopes in the treatment of such variants of aplastic anemia in children are associated with bone marrow transplantation.

Early symptoms of acquired aplastic anemia include general weakness, fatigue, pain in the bones and joints, hemorrhagic syndrome 11( nasal bleeding, hemorrhages in the skin).Gradually, the pallor of the skin and mucous membranes increase. The liver is somewhat exaggerated. Spleen and peripheral lymph nodes are not enlarged. In the blood there is a triphyrox cytopenia: normochromic-normocytic anemia with a marked decrease in the hemoglobin concentration( <70 g / l), but normal hematocrit and erythrocyte indices, granulocytopenia( 0.56 ± 0.2x 109 / l) and thrombocytopenia( 25,0 ± 11.1 109 / l).In the case of computer morphometry of cells in peripheral blood smears, pronounced changes in the shape of erythrocytes were noted in patients with AA: an increase in the average curvature, contrast, a decrease in the average and total optical density( OD), a change in the ratio of the OD gradients of the ascending and descending sections of the biconcave disk, and an increase in the variability of the OD distribution. At the same time, it was noted that with the same surface area and normal hemoglobin content in erythrocytes( 33 pg) in a peripheral blood of a part of patients, a pool of cells with a low, less than 10 pg saturation with hemoglobin appears, which makes them similaron erythrocytes of patients with clinical manifestations of refractory anemia( RA).With AA, as in RA, an increase in the dispersion of the erythrocyte distribution curves in size and in the hemoglobin content is observed, as well as a direct relationship( r = 0.98, p <0.01) between the proportion of altered peripheral blood cells and the content of PIC-positive elements inbone marrow. The high incidence of SHIC-positive erythrocaryocytes( 23% vs. 3-8% in controls) suggests the contribution of ineffective erythropoiesis to the pathogenesis of AA, but the effectiveness of subsequent immunosuppressive therapy of the disease is not determined by the magnitude of this indicator, but depends solely on the number of ringed sideroblasts in the bone marrow:at 6-8% of these forms, treatment with cyclosporin A does not give a positive result. The content of serum iron in most patients is increased, saturation of transferrin is close to 100%.In the study of ferrokinetics with the help of radioactive iron, the elongation of the time of excretion of iron from the plasma and the reduction of erythrocyte ferritin are revealed - another confirmation of the inefficiency of erythropoiesis. The lifespan of erythrocytes, measured with radioactive chromium, is usually somewhat shorter. Sometimes the level of fetal hemoglobin increases to 15%.

The severity of the disease is assessed by the content in the peripheral blood of granulocytes and platelets( the criteria of Comitta and the European AA Study Group).Severe AA refers to cases where the number of granulocytes is & lt;0.51 x 109 / l, and platelets & lt;20 x 109 / l.; The remaining patients are conditionally diagnosed with a non-severe form of the disease.

The bone marrow pattern in the initial period of the disease is characterized by some reactive hyperplasia of the erythronomoblastic sprout with a violation of the ripening of red cells. Later, the bone marrow is gradually emptied, the red sprout is reduced, the number of cells of the lymphoid type increases. Especially evident is the degree of bone marrow emptying and replacement of myeloid fatty tissue in lifetime histological preparations( trepanobiopsy).The course of the disease is acute, subacute and chronic. Sometimes spontaneous remissions occur.

The prognosis in most cases of the disease is unfavorable, it depends on the degree of damage to the bone marrow and the phase of the pathological process. The criterion for responding to therapy is the dynamics of hematological parameters( hemoglobin, granulocytes and platelets) and a decrease in the dependence on transfusion of erythrocyte and platelet masses on the background of treatment. The following tactic is recommended as an algorithm of the combined therapy program for patients with AA: in the first stage, antilymphocytic immunoglobulin( ALG) is prescribed, with intolerance or absence of the drug, splenectomy is performed;two weeks after the beginning of the course of therapy of ALG after the relief of serum sickness, a 12-month course of therapy with cyclosporin A begins;in 6-12 months, if clinico-hematologic response, the program includes splenectomy, but treatment with cyclosporine continues( in refractory patients, lymphocytosis can be used.)

This disease in adult patients - acquired, characterized by a sharp inhibition of erythroid hemopoiesis. Deep anemia of the normochromic type due to the almost complete suppression of erythropoiesis is accompanied by a severe hypoxemic complex of symptoms. You can detect antibodies to erythrocaryocytes. Therefore, preference is given to immunosuppressive therapy( cicosporin A) in combination with a replacement erythrocytic mass under the control of iron metabolism in order to avoid secondary hemosiderosis and additional oppression of erythropoiesis. When the ferritin level is raised more than 400 μg / l, desferal therapy.

Anemia, although its severity does not always correlate with the clinical manifestations of the underlying disease, may be one of the first manifestations of a malignant tumor. Almost 50% of patients with multiple myeloma hemoglobin at the time of diagnosis is below 100.5 g / l, and in 40% of patients with lymphosarcomas, less than 120 g / l. After several courses of chemotherapy, the value of this indicator falls even lower.

Anisocytosis, poikilocytosis, hypochromia and pathological erythrocytes are noted in all patients with leukemia. The appearance of anemia after adjuvant chemotherapy of the tumor in 2.95 times increases the risk of developing a local relapse.

The causes of anemia in oncology can be bleeding, vitamin and iron deficiency, bone marrow damage, hemolysis of red blood cells. Mediators of inflammation shorten the life span of red blood cells from 120 days to 90-60 days. Antitumor drugs, in particular, platinum, having a myelotoxic effect and blocking the production of erythropoietin, suppresses erythropoiesis. Reduction of blood formation in turn affects the quality of life of the cancer patient, complicates the course of the underlying disease, worsens the effectiveness of specific therapy.

Anemia in cancer patients may be mild in terms of severity( Hb below 110 g / L), moderate( Hb from 110 to 95 g / l), expressed( Hb from 80 to 60 g / l) and heavy( Hb below 65 g/ l).Her usual symptoms - depression, weakness, sleep disturbances, dizziness, tachycardia - often hide behind the clinical manifestations of the tumor. It turned out that the lower limit of the physiological norm of hemoglobin is a real boundary between the clinical norm and pathology.

Concentration of hemoglobin is a prognostic factor in the chemotherapy of cancer patients, equivalent to the size of the tumor, the stage of the disease and the type of treatment. Possible mechanisms of the negative influence of a low level of Hb concentration on the survival of patients include a disturbance of tumor oxygenation, which reduces the effectiveness of chemo- and radiotherapy.

Exceeding the rate of tumor growth over the ability of erythrocytes to deliver tissues an adequate amount of oxygen leads to tissue hypoxia. It is known that the tumor tissue is oxygenized worse than the surrounding tissue. The fibrosarcom model shows that hypoxic cells are 2 to 6 times less sensitive to the effects of cytostatics.

As anemia therapy in tumor pathology, transfusions of blood products and the administration of erythropoietin are shown. A new stimulant of erythropoiesis, Darbopoietin, is being actively studied.

To the group of anemia arising from increased blood destruction there are a variety of hemolytic anemia, united by one common symptom - a shortening of the lifespan of red blood cells.

All forms of anemia associated with hemolysis of peripheral blood erythrocytes belong to the group of regenerative anemia with normoblastic type of erythropoiesis. Hemolytic anemia develops only when the bone marrow is unable to compensate for the missing red blood cells. Moreover, the mechanism of development of this type of anemia is more often associated with hemolysis of peripheral blood erythrocytes and much less often with the death of ripening erythroid cells in the bone marrow. The appearance of pathological hemolysis is mainly due to two reasons:

There are extravascular and intravascular hemolysis. At the heart of clinical manifestations of the majority of hemolytic anemias is extravascular hemolysis. Immunologically, this variant of erythrocyte destruction is provided by so-called thermal antibodies( IgG) 12, the target of which are erythrocytes with small defects. Extra-vascular hemolysis occurs in the spleen( splenomegaly), its effectors are macrophages. Macrophages carry receptors to the Fc-fragment of immunoglobulins, therefore the red blood cells covered with these antibodies bind and are destroyed by them. Since, on the other hand, macrophages carry the receptor to complement components, the most expressed hemolysis of erythrocytes is observed when both membranes are present simultaneously with both IgG and СЗb.

Intravascular hemolysis is the effect of cold IgM antibodies in most cases. The complement binding sites located on the Fc fragments of the IgM molecule are located at a short distance from each other, which facilitates the fixation of the components of the membrane-antagonizing complex on the surface of the erythrocytes. The formation of a membrane-binding complex leads to swelling and destruction of erythrocytes. Intravascular hemolysis, a mechanism of erythrocyte destruction with large defects, is performed in well-provided blood supply organs, for example, in the liver. Accumulation in the plasma of patients with indirect bilirubin in any variant of hemolysis of erythrocytes is associated with the inability of the liver to convert the excess of hemoglobin released from the destroyed red blood cells into glucuronide and isolate it through the gallbladder into the duodenum. In this case, pigmentary stones( chronic hemolysis) are formed in the gallbladder, and stercobilin is released with feces. In turn, the excess of hemoglobin binding capacity of plasma haptoglobin leads to hemoglobinuria, urobilinogenuria and hemosiderinuria. The appearance of hemosiderin in the urine is one of the main signs of intravascular hemolysis of erythrocytes.

The main criterion of hemolysis of erythrocytes is the life span of erythrocytes in 51Cr. The ratio of the sequestration of erythrocytes in the organs helps to clarify the hemolytic status: 1: 3 over the liver and spleen - extravascular hemolysis, 3: 1 - intravascular( 1: 1 norm).The remaining laboratory parameters serve as an indirect confirmation of hemolysis:

The clinical course of hemolytic anemia can be acute, chronic or epizootic. Less severe hemolysis creates a picture of hemolytic crises: chills, fever, jaundice, back and stomach pain, hemoglobinuria, prostration, shock. Anemia with chronic course of the disease is sometimes amplified. Oppression of erythropoiesis during infectious complications, leads to the development of aplastic crisis.

Anemia is usually normochromic-normocytic, with the exception of cases when increased production of reticulocytes contributes to an increase in the value of MCV.Extra-vascular hemolysis can cause the appearance of spherical cells in the smears of peripheral blood with increased hemoglobin concentration( as a consequence of the release of red blood cells from narrow couplings of RES - the reticuloendothelial system).With intravascular hemolysis due to mechanical damage to erythrocytes, schizocytes( fragments of erythrocytes) are detected.

The protocol of therapy in each individual case is determined by the hemolytic status of the patient. In hemoglobinuria and hemosiderinuria, replacement therapy with iron is shown, with sequestration of erythrocytes in the spleen - splenectomy.

Depending on the causes of the occurrence, hereditary and acquired hemolytic anemia is distinguished.

Hereditary hemolytic anemias are divided into three large groups:

The main pathogenetic link of hemolytic anemia of this group is the genetic defect of cytoskeleton proteins( spectrin, for example), so that the bone marrow of a de novo patient develops erythrocytes of altered form and elasticity, for example, ellipocytes or spherocytes. This distinguishes hereditary membranopathies from autoimmune hemolytic anemia, where the same spherocytosis is secondary. As a result, erythrocytes lose the ability to deform in narrow sections of the blood stream, in particular, when passing from the sinus spacing to the sinus spaces. Losing excess water, altered red blood cells constantly expend energy, consuming more glucose and ATP.These processes, along with mechanical damage, for example, spherocytes in the spleen sinusoids, lead to cell wear and shorten their life to 12-14 days. Round cells become the target of macrophages of the spleen and extravascular hemolysis arises. Permanent hemolysis of erythrocytes leads to hyperplasia of the cells of the pulp of the spleen and to an increase in the size of the organ.

The cause of membranopathies are congenital mutations of the autosomal dominant type. In practice, the most common of them is hereditary microspherocytosis( Minkowski-Schoffar's disease).Microspherocytosis was described by Minkowski in 1900.In most cases, the first signs of the disease are revealed in adolescence or adulthood. The disease is characterized by the so-called hemolytic crises. During the exacerbation, weakness, dizziness, fever, hemolysis, jaundice and mild anemia with reticulocytosis( against the background of infections increases to aplastic crises), splenomegaly, the concentration of indirect bilirubin reaches 50-70 μmol / l. The severity of jaundice depends, on the one hand, on the intensity of hemolysis, and on the other hand on the ability of the liver to conjugate free bilirubin with glucuronic acid. In the urine, bilirubin is not detected, since free bilirubin does not pass through the kidneys. Cal is intensely colored in a dark brown color due to the increased content of sterocilin( daily excretion exceeds the norm by 10-20 times).Anemia is normochromic in nature. The number of erythrocytes varies from 3.0 to 4.0 x 1012 / l, falling during aplastic crises below 1.0 x 1012 / L, moderately reducing the hemoglobin content. Spherocytes( round erythrocytes without central clearing) in the peripheral blood smears of patients are characterized by a decrease in the mean diameter( less than 7.2-7.0 μm) against the background of the normal mean volume and the increased value of MCH.The curve of distribution of erythrocytes in size( the Price-Jones curve) on the graph is shifted to the left. In a low osmolar medium, the spherocytes are less brittle than ordinary red blood cells: the beginning is 0.7-0.6%, the end is 0.4% at a rate of 0.48%, and 0.22% NaCl, respectively. The index of spherocytosis falls below 3;the RDW value exceeds 12%( anisocytosis).Reticulocytosis - 15-30%.

Bone marrow in the flat and tubular bones is hyperplastic due to the erythroid sprout, erythrophagogocytosis with reticular cells is noted. In the spleen there is a pronounced blood filling of the pulp, hyperplasia of the endothelium of the sinuses, a decrease in the size and number of follicles. Hemosiderosis is often detected in the liver, bone marrow, and lymph nodes. Hyperplasia of the erythroid bone marrow during aplastic crises is replaced by aplasia. The negative result of the direct Coombs test allows to exclude autoimmune hemolytic anemia.

Introduction of glucose is able to correct hemolysis. A good therapeutic effect is provided by splenectomy, especially in patients under the age of 45 years.

Enzymopenic( fermentopenic) anemia or erythrocyte enzymes occur as a result of a hereditary deficit of a number of erythrocyte enzymes( a recessive type of inheritance).Characterized by the normal form of erythrocytes, the tendency to macrocytosis, normal or increased osmotic resistance of erythrocytes

Deficiency of glucose-6-phosphate dehydrogenase( G-6-PD).The integrity of red blood cells is sensitive to the accumulation in them of such a natural metabolite as hydrogen peroxide. Damage to cells occurs when certain oxidant substances with food( horse beans and chubby plants) or with medicinal preparations( sulfonamides, derivatives of salicylic acid, etc.) enter the body, and also develop against influenza or viral hepatitis. However, usually the compensation

torn mechanism, and hydrogen peroxide is transferred to harmless water. The enzyme that catalyzes the reduction of hydrogen peroxide is called glutathione peroxidase. The enzyme supplies glutathione, which requires the recovery of nicotinamide dinucleotide phosphate( NADP), generated by the reactions of the pentose phosphate pathway. The first reaction of this hexosomonophosphate shunt is the dehydrogenation of glucose-6-phosphate soluble in the erythrocyte cytoplasm by the enzyme glucose-6-phosphate dehydrogenase. The enzyme deficiency is inherited as a trait linked to the X-chromosome. With the activity of G-6-FDH suppressed due to this, overloading by oxidation products in patients weakens or even turns off the compensatory mechanism. When you take the usual therapeutic doses of the above drugs or beans( "favism" in children), hemoglobin is oxidized, the heme is lost from the hemoglobin molecule, the globin chains are precipitated in the form of Heinz bodies. Erythrocytes are released from the bodies of Heinz in the spleen. At the same time part of the membrane substance of erythrocytes is lost, which leads to intravascular hemolysis. The hemolytic crisis develops sharply and ceases in 2-3 days only after all red blood cells with deficiency of G-6-FDH have collapsed( the phenomenon of "self-limitation" of hemolysis).Hemolysis undergoes more "adult" erythrocytes. Hemolytic crises occur against a background of fever, viral or bacterial infections, diabetic acidosis. There is pronounced dyspnea, palpitations, a collapse is possible. A characteristic symptom is a secretion of dark urine down to black, which is associated with intravascular decay of erythrocytes and release of hemosiderin by the kidneys. In some cases, due to obstruction of the renal tubules by the products of the decomposition of hemoglobin and a sharp decrease in glomerular filtration, acute renal failure may develop. At an objective research jaundice of integuments and mucous membranes, an increase in a lien, less often a liver are marked.

The vast majority of patients are men, but homozygous women are also ill. There are two basic mutant forms of the enzyme. One of them is common among Europeans in European countries( Form B), the other is among the Negro population of Africa( Form A).The disease occurs in about 10% of African Americans and is less common among immigrants from the Mediterranean countries( Italians, Greeks, Arabs, Sephardic Jews).In the CIS, the G-6-FDG deficiency is the most widespread among the inhabitants of Azerbaijan. In addition, the carrier of the pathological gene is found in Utadjik, Georgians, and Russians. Persons with deficiency of G-6-FDH, as well as patients with sickle-cell anemia, die less often from tropical malaria, which causes the prevalence of this pathology in the "malarial" areas. In patients of the white race, crises are extremely difficult, leading to hematuria, kidney failure, and can end fatal. Unlike sickle cell anemia, the disease can manifest itself from birth, and the severity of its clinical symptoms is determined only by the variant of the gene mutation.

During the crises, regenerative anemia develops with a drop in hemoglobin concentration of up to 30 g / l, reticulocytosis and the appearance of normoblasts;in the smears of peripheral blood can be seen erythrocytes with Heinz bodies - small rounded single or multiple inclusions formed by denatured hemoglobin. Purple-red bodies of Heinz are detected in erythrocytes with supraltal coloring with methyl violet. Similar inclusions in erythrocytes appear and when poisoning with hemolytic poisons. In the bone marrow, hyperplasia of the erythroid germ and erythrophagocytosis are observed.

Persons at risk for hemolysis should not take food or drugs that cause it to develop. The prognosis of the disease with the development of anuria and renal failure is unfavorable. With lightning-fast forms of the disease, death comes from shock or acute anoxia.

Pyruvate kinase deficiency( PC).In erythrocytes there are no mitochondria and, therefore, aerobic glycolysis( Krebs cycle) is not possible in them. The source of ATP, which is primarily needed to support an ATP-dependent potassium-sodium pump, is anaerobic glycolysis( the Empeden-Meierhof pathway), becauseThe hexosone monophosphate shunt does not produce high-energy phosphate bonds. By removing sodium from the cell and introducing potassium into it, the pump must be provided with energy. The comparatively rare deficiency of pyruvate kinase, the enzyme of the Empeden-Meierhof pathway, reduces the energy potential of the erythrocyte. The removal of sodium consumes more energy( glucose, ATP) than normal. In the blood, where glucose is enough, the sodium pump still provides removal of excess sodium. In the inter-sinus spaces of the spleen, where the glucose content is reduced, sodium is not excreted, and this leads to osmotic hemolysis of the erythrocytes. In contrast to the G-6-FDG deficiency, PC deficiency is autosomal recessive, causes hemolytic anemia only in homozygotes and is not manifested by episodes, but as a chronic disease. The quantification of ATP and diphosphoglycerate helps to clarify the diagnosis.

In blood smears, a small number of serrated spherical erythrocytes can be detected. In such cases splenomegaly is observed. With the development of persistent transfusion dependence, splenectomy is advisable, however, after it there is only a slight improvement, but anemia persists.

Hemoglobinopathies are combined by genetic, biochemical and physiological signs of hereditary disorders of hemoglobin synthesis. Some types of hemoglobinopathies are of scientific interest only, others( sickle cell anemia and some of thalassemia) threaten the life of patients, and finally, third( most thalassemias, hemoglobinoses E and O) catch doctors unawares and cause collapse of hopes in unfortunate patients. Each pathology included in this group can not be considered an independent nosological unit. Some hemoglobinopathies, where structural hemoglobin rearrangements entail inadequate production of erythrocytes, are included in thalassemia( a breakdown in the synthesis of polypeptide chains), but not all hemoglobinopathies and thalassemia are hemolytic anemia. Thalassemia is a genetic defect, as a result of which an unnaturally low amount of polypeptide chains of globins is formed in the synthesis of hemoglobin. The defect can affect separately a-, β -, γ - or 5-chains or change their combinations, but never affects a- and P-chains together. The result is hypochromic macrocytic anemia, which develops as a result of satiation of red blood cells with stored chains that can not stochiometrically communicate. The effect is contradictory: on the one hand, death and destruction of cells in the bone marrow( ineffective erythropoiesis), on the other hand hemolysis of erythrocytes in peripheral blood.

Conditionally hemoglobinopathies are divided into qualitative and quantitative. Qualitative hemoglobinopathies are accompanied by a hereditary violation of the primary structure of hemoglobin, quantitative ones are characterized by a decrease in the rate of synthesis of polypeptide chains of globin.

Phenotypic manifestations of qualitative hemoglobinopathies may result from the substitution of one amino acid for another( for example, in HbS and HbC and most other altered hemoglobins), the replacement of part of the amino acid sequence( Hb Gun Hill), the abnormal hybridization of two chains( Hb Lepore), or the extension of one globinchains( Hb Constant Spring).As a result, abnormal hemoglobins appear: HbGPhiladelphia, HbS, HbC, HbFTexas, or HbA2Flatbush. Hemoglobins HbS and HbC are accompanied by the most severe hemoglobinopathies.

There are polypeptide chains of globins that are very sensitive to amino acid substitutions. For example, replacing glutamate at position 6 with a polypeptide [3-chain with valine or lysine leads to the formation of hemoglobins S and C, which respectively form intra-erythrocyte tactoids and crystals and lead the cell to hemolysis. On the other hand, the replacement of glutamate, asparagine and threonine with lysine at position 59 of the polypeptide chain leads to the formation of polypeptide chains, which do not occur in normal hemoglobin HbA.Usually abnormal hemoglobins of different electrophoretic mobility are denoted by letters. The first of these was hemoglobin, found in sick sickle cell anemia( HbS), and then the names were assigned in alphabetical order as new variants were discovered. Various structures of hemoglobins with the same electrophoretic mobility are designated by the locality where they are found.

Without going into stereochemical details, it can be said that the pathological structure of hemoglobins is detected by one of the following manifestations:

1. Increased affinity to oxygen, which is possessed by hemoglobins formed as a result of mutation of part of amino acid sequences:

Hemoglobin binds oxygen in the alveoli of the lungs, thencover its consumption in tissues. When tissue hypoxia occurs, the kidneys most sensitive to it throw out erythropoietin and provide extra-production of erythrocytes by the bone marrow, stimulating erythropoiesis even before anemia develops: the total mass of red blood cells, hemoglobin concentrations and hematocrit increase. However, abnormal hemoglobins, including Hb Chesapeake and HbJ Capetown, have an increased affinity for oxygen, with difficulty giving it to tissues.

2. Reducing the affinity of hemoglobin for oxygen. If hemoglobin has lost its ability to be oxygenated in the lungs, the proportion of oxygenated Hb for a given pO2 decreases. Cyanosis occurs when the concentration of such hemoglobin in capillary blood increases to 50 g / l. To hemoglobins with a reduced ability to saturate with oxygen include Hb Seattle, Hb Vancouver and Hb Mobile. They can not adequately meet the need for tissues and cells in oxygen.

3. Methemoglobinemia. A special class of hemoglobins with a reduced affinity for oxygen is characterized by the presence of a prosthetic group, which contains iron( Fe +++).Among the symptoms of the disease, cyanosis is a hallmark.

There are variants of metahemoglobinaemia, other than hemoglobinopathies:

Usually, both are stopped by the appointment of antioxidants.

4. Unstable hemoglobins. With some changes in the polypeptide chains of globins, unstable hemoglobins appear and then, with the supratinal color of the erythrocytes with a brilliant cresol blue, the Heinz corpuscles are visible. These inclusions are attached to the inner membrane of the erythrocyte, depriving the cell of deformability, especially in the narrow sinuses of the spleen, and lead to the development of hemolytic anemia. To unstable hemoglobins include Hb Gun Hill, Hb Leiden and Hb Kc1n.

5. Sickling and crystallization. These phenomena are observed in carriers of hemoglobins HbS and HbC.

HbS hemoglobin gene is found in natives of tropical Africa( 40%) and African Americans( 8%).Less often it can be found in other areas, including the Mediterranean and the Caucasus. It is expressed in heterozygotes( gene inheritance from one of the parents), causing sickle cell hemolytic anemia and vasocclusion. HbS hemoglobin is biochemically unstable, pre-precipitates in solution, forming long spindle-shaped structures called tactoids. Due to this, red blood cells become characteristic sickle-shaped. Only deoxygenated forms of hemoglobin HbS, and in typical cases heterozygotes make up 30-40% of the total amount of hemoglobin16, form tactoids. Since the appearance of hemoglobin HbS is the result of the mutation of the polypeptide chain of globin with the replacement of hydrophilic glutamate in the 6th position( 3-depi globin by the hydrophobic amino acid valine( in electrophoresis the chain moves to the anode more slowly than the molecule of HbA), the symptoms of the disease appear after the newbornthe baby will reach the age of six months, that is, when fetal hemoglobin ceases to be the main carrier of oxygen in the body. Disease in the African population of patients is somewhat mitigated by coexistence geneticallyx anomalies Examples:

Sickle cell anemia is a serious disease in which vasoaclusis is added to hemolytic anemia. The first description was made by the cardiologist Herrick( Chicago) in 1910.

In smears of peripheral blood of patients - normochromic-normocytic anemia: erythrocytes - 2,0-3,0х 1012 / l, hemoglobin - 7-10 g / l, MCV about 22 fl, MCSN less than 30 g / l, reticulocytes 10-20%, poikilocytosis due to the presence of sickle erythrocytes, a few target cells, Jolly's body. The lifespan of erythrocytes is 10-20 days.

The following symptoms prevail in the clinic:

1. Effects of hemolysis - anemia, mild jaundice, as a result of the accumulation of bilirubin, cholelithiasis due to excess bilirubin salts in the hepatobiliary system, aplastic and hemolytic crises. Episodes of aplastic crises can also occur in patients who are not carriers of pathological variants of hemoglobin, for example, during viral infections, but with sickle cell anemia the life span of erythrocytes is shortened, so in this situation the hematocrit falls sharply and there are no reticulocytes. Catastrophic drop in the level of hematocrit and jaundice with increasing reticulocytosis - haemolytic crises.

2. Effects of vasocclusion:

Treatment of the disease is symptomatic, becausethere is no effective therapy. Typically, treatment of crises consists of oral or intravenous hydration and the administration of painkillers, including drugs. Indications for component blood transfusion are symptoms of cardiopulmonary insufficiency and a drop in hemoglobin concentration. Long-term infusion therapy is indicated for the prevention of cerebral hemorrhage in persons younger than 18 years old who previously tolerated such complication of the disease. The purpose of such transfusions is to reduce the proportion of sickle erythrocytes below the level of 30% with a 40% hematocrit. Prevention of infections is done by prescribing antibiotics. Chelation( desferal) is used for secondary hemosiderosis and an increase in serum ferritin of 1500 μg / l. Splenectomy is indicated in the development of leuko- and thrombocytopenia, especially with hemorrhagic syndrome.

The gene for Hb C prevails in the African American population, but not at such a high frequency as the sickle cell gene - 2-3%.Hemoglobin C does not form tactoids, but forms obtuse crystalloids. It differs in the structure of the fourth peptide of the hemoglobin molecule, in which, in the sixth position, lysine is substituted for glutamic acid. As a result, the life time of red blood cells is shortened, but hemolysis is not as severe as in sickle-cell anemia and there is no such devastating vasoocclusion. The center of distribution of gene C is the northern part of Ghana. The frequency of heterozygosity is from 15% to 28%.Targeted erythrocytes( from 30% to 100%) are present in homozygotes and some heterozygotes in peripheral blood smears, but pathogenic crystals appear rarely. Anemia in homozygotes is of normocyte character, the number of reticulocytes is somewhat increased, normoblasts can be found. When electrophoresis - all hemoglobin refers to hemoglobin C. In patients often enlarged spleen, there are often pain in the abdomen, in the joints, but painful crises, as with sickle-cell anemia, there is no. Jaundice is moderate, sometimes there are episodes of sequestration of erythrocytes in the spleen and a sharp decrease in their number in the peripheral blood. The prognosis of HbC-hemoglobinopathy is favorable. True, some patients can inherit from one parent HbS, the other - HbC hemoglobin. As a result, Hb SC disease develops clinically in terms of the severity of the course occupying an intermediate place between the sickle cell anemia and HbC hemoglobinopathy, with the exception of retinal vascular lesions, when its prognosis is worse than the consequences of sickle cell anemia.

Hemoglobin E is a general mutation of the p-chain globin for patients in Southeast Asia: in Kampuchea, Thailand, Burma, Bengal, from the Veddas of Sri Lanka, in northeastern Malaya, in the population of Kalamantan and Sulawesi.

Thalassemia ( Mediterranean anemia) is a group of hereditary chronic microcytic anemias. Prenatal diagnosis of these diseases based on gene mapping using recombinant DNA is becoming a daily practice.

The causes of thalassemia and the nature of their clinical symptoms were elucidated after the genetics of hemoglobins in the postnatal period became clear.

Small thalassemia. Heterozygotes with any variants of p-thalassemia genes. The disease is transferred without clinical manifestations, or patients suffer from borderline anemia: the number of red blood cells is 3.8 x 1012 / l, hemoglobin - 111.5 g / l, hematocrit - 0.35 l / l17.There is anisocytosis with microcytosis( MCV = 80 fl), and an increased concentration of hemoglobin HbA2.At the time of marriage such patients should carefully select a partner.

Large thalassemia or anemia of Cooley. Homozygotes( with the exception of the Negro race) develop a picture of severe anemia, corresponding to the classical description of Cooley, caused by the genes of P-thalassemia. The number of erythrocytes with increased osmotic resistance drops to 3.0 x 1012 / l, hemoglobin - to 62.0 g / l. Reticulocytes make up 0.6%.There are anisocytosis with a predominance of microcytics( MCV - 60 fl), hypochromia( MCH - 25 pg and MPS - 280 g / l), poikilocytosis with target, drop-shaped erythrocytes and schizocytes;basophilic puncture. The concentration of indirect bilirubin in the serum is increased, and serum iron and ferritin levels overlap the normal values. There are no signs of erythroid hyperplasia in the bone marrow. The prognosis of the disease is unfavorable.

Intermediate thalassemia. Relatively mild course of the disease in the presence of the gene( 3+( Negro) or other mixed mutation types. The number of erythrocytes averages 3.57 ± 0.26 x 1012 / l, hemoglobin 79.38 ± 2.8 g / l,and its content in erythrocyte ranges from 13.9 to 46.4 pg, transfusion therapy helps, but the transformation of the disease into greater thalassemia is possible with age

Table 1. Basic differential diagnostic signs of hypochromic anemia

Therapy of large thalassemia with blood transfusions may be one of thecauses of death of patients.and are supported by transfusions until about 10 years of age, after which, as a result of circumvention of the normal ways of ingestion and excretion of iron, symptoms of hemochromatosis appear( first the excess of iron phagocytes the cells of the reticuloendothelial system and then it is deposited in the parenchymal organs). The most toxic excessiron for the pancreas, liver, myocardium, adrenal and gonadal glands, which is expressed in diabetes, hepatitis and cirrhosis, cardiovascular insufficiency, insufficiency of the adrenal glandin and delayed puberty. Lethal outcomes in the second or third decade of life most often occur because of cardiovascular failure, so blood transfusion should limit or remove excess iron using complexing agents. Splenomegaly somewhat changes the situation - the need for blood transfusions decreases.

α -thalassemia combines the most common hemoglobinopathies and thalassemia. One of its forms, often encountered among African Americans, is characterized by such a soft current that it is not only almost impossible to detect in adult heterozygotes, but also in homozygotes it proceeds asymptomatically with insignificant laboratory signs. Other forms are so severe that they end fatal still during the intrauterine period.

Two concepts for the development of a-thalassemia can be considered:

Different from p-thalassemia, a-thalassemia develops before the fetus is born, becauseThe a-polypeptide chains of globins are embedded in all hemoglobins, beginning with the most ancient Hb Gower and Hb Portland. Because of this, carriers of the genes of a-thalassemia still in the prenatal period underproduce the hemoglobins Hb Gower 2, HbF, HbA and HbA2.HbA2 hemoglobin can not be a diagnostic marker of a-thalassemia.

In the differential diagnosis of the disease, it is important to exclude other causes of microcytosis and to determine erythrocyte indices from relatives.

Usually by the end of the first year of life this disease manifests itself as chronic hemolytic anemia of moderate severity. The average level of total hemoglobin is 86 g / l. Hemolytic crises develop against the background of intercurrent infections or after taking various medications, hemoglobin falls to 40 g / l. There is a lag in physical development, the Mongoloid type of face, expressed less than with p-thalassemia. Hepatosplenomegaly, jaundice with increased indirect bilirubin, iron-deficiency pathology and cholelithiasis are possible. In the analysis of peripheral blood, hypochromic anemia, microcytosis, reticulocytosis, aniso- and poikilocytosis, target red blood cells are noted. The values ​​of erythrocyte indexes MCV and ICSU are reduced. When hemoglobin is electrophoresed on an alkaline buffer, HbH is determined, the amount of which varies from 5% to 30%, and also Hb Bart's in different amounts. The content of hemoglobin H b A2 is decreased, and fetal hemoglobin is within 0.3-5%.The ratio a: P = 0.57.During crises patients need component hemotransfusion. In a number of cases, splenectomy gives a good effect.

Fetal hydropsis syndrome with Hb Bart's. With a-thalassemia-1, the production of a-polypeptide chains of globins is excluded. Only hemoglobins Hb Bart's, HbH and Hb Portland are determined in patients. The death of carriers of these hemoglobins occurs either in the prenatal period, or immediately after birth. Autopsy demonstrates extramedullary hematopoiesis in virtually every parenchymal organ. On examination, a pale, swollen fetus with a massive and loose placenta;petechiae on the skin, lung development defects, the heart is enlarged with hypertrophy of both ventricles, the thymus and spleen are enlarged, ascites and effusions in the pleura, pericardium are determined. In various organs on the ground of heavy hemolysis there are deposits of hemosiderin. The level of hemoglobin is 30-100 g / l, and in blood smears - pronounced aniso- and poikilocytosis, target red blood cells, erythroblasts and hypochromic macro-cells( the average volume of erythrocytes is increased, the average concentration of hemoglobin is reduced).

Acquired hemolytic anemia can be divided into two groups:

Immune hemolysis is caused by both allo- and autoantibodies. The development of autoantibodies to erythrocytes can be caused by the following reasons:

It is known that red blood cells carry on their surface about 400 antigens;plasma proteins are also characterized by a large antigenic diversity. The mechanism of development of hemolytic anemia in such cases is explained by the hyperreactivity of the reticulo-endothelial system, mechanical damage or infection, as well as exposure to chemicals or hemolytic poisons.

Autoimmune hemolytic anemia( AIGA) in a number of immune hemolytic anemia is more common than others. The development of the disease is associated with the appearance in the patient's body of antibodies that can lyse not only red blood cells of peripheral blood, but erythro- and normoblasts of bone marrow and even early erythron precursor cells.

Autoantibodies to erythrocytes belong to different types. According to the serological principle, the following forms of AIGA are distinguished:

The most common anemia with incomplete thermal agglutinins( 70-80%).The autoimmune nature of anemia is demonstrated by an antiglobulin test( Coombs test) in which heterologous antiglobulin antibodies react with immunoglobulins, and complement components with the patient's erythrocytes( direct Coombs reaction).It is also possible to detect free antibodies in the patient's blood plasma by mixing its plasma with normal red blood cells( indirect Coombs reaction).As a rule, the severity of the direct reaction positively correlates with the amount of IgG and complement molecules fixed on the erythrocyte surface, and not with the intensity of cell destruction. The positive results of the indirect Coombs reaction( the presence of free anti-erythrocyte antibodies) without confirmation in the direct test do not yet indicate the immune nature of hemolysis, but only confirm the presence of alloantibodies, which may also appear during pregnancy, after blood transfusions or in cross reactivity with phytohemagglutinin.

Autoimmune hemolytic anemia caused by extravascular hemolysis( thermal antibodies) may be primary( 55%) or secondary: with hemoblastoses( 20%), use of drugs( 20%), collagenoses and viral infections( 5%).This form of hemolytic anemia can be very severe. Mortality of primary autoimmune hemolytic anemia is 4%.The prognosis for secondary autoimmune hemolytic anemia depends on the underlying disease. Anemia often develops imperceptibly. In severe cases, hemolytic crises occur. After 24 hours after the onset of acute massive hemolysis, jaundice appears. With palpation, splenomegaly can be detected.

Character of anemia is normochromic-normocytic, regenerative: the number of reticulocytes is increased, polychromasia, spherocytes occur and sometimes - schizocytes, normoblasts. Oppression of erythropoiesis in viral infection is accompanied by the development of aplastic crisis( a decrease in the level of reticulocytes).In urine, urobilinogen and hemoglobin are determined. Differential diagnosis is based on the results of direct Coombs test: in 2-4% of patients with clinical manifestations of autoimmune hemolytic anemia, the direct Coombs test is negative;The indirect Coombs test is positive in 60% of patients with autoimmune hemolytic anemia. The relationship between the severity of haemagglutination in the Coombs sample and the severity of hemolysis is not. Erythrocytes can be covered only with IgG agglutinins( 20-40% of cases), immunoglobulins and CbS complement components( in 30-50% of cases) and only with complement components( in 30-50% of cases).The determination of the type of molecules fixed on the surface of erythrocytes sometimes allows us to clarify the diagnosis. So, the diagnosis of systemic lupus erythematosus is unlikely, if red blood cells are covered only with IgG.It is important to determine the class of antibodies fixed on the erythrocyte surface. If only IgG is detected, they are most likely directed against the Rh system antigens. If antibodies of different classes are detected, the patient is probably sensitized against several erythrocyte antigens, which makes the selection of a donor very difficult.

Treatment of hemolytic crisis should begin immediately. Immunosuppressive therapy of the first line - prednisolone at a dose of 1 mg / kg of body weight per day to a stable effect( course no more than 2-4 weeks), followed by a gradual decrease in the dose until complete cancellation after normalization of clinical-hematological and serological indicators. Second line

Perhaps the treatment with cyclosporin A indicates a positive effect of the use of a-interferon preparations.

Secondary autoimmune hemolytic anemia primarily treats the underlying disease. In children, this form of the disease is usually caused by a viral infection and quickly passes. In other cases, anemia proceeds undulating. During exacerbations, a significant decrease in the level of hemoglobin and often urgent help is required.

Autoimmune hemolytic anemia caused by intra-vascular hemolysis( cold antibodies).There are two forms of this disease:

In both cases intravascular immune hemolysis can be both primary and secondary. In the latter case, it develops against a background of viral infections( eg, infectious mononucleosis), malaria, mycoplasmal pneumonia, hemoblastosis or collagenosis.

Cold agglutinins are more often IgM, less often - a mixture of immunoglobulins of different classes, they are active at a temperature below 37 ° C.When the blood enters the areas of the body with a low temperature( the temperature of the skin of the limbs can normally drop to 30 ° C), cold agglutinins are fixed on the surface of red blood cells and, by binding complement, cause hemolysis, the intensity of which depends on the temperature. Reacting with antigens in a wide range of temperatures, cold antibodies remain on red blood cells and when blood returns to the main vessels, where a higher temperature enhances fixation of the complement. Cold agglutinins that show activity in a narrow range of temperatures, when blood is returned to the main vessels, are separated from the erythrocytes. They are more typical for viral infections and mycoplasmal pneumonia.

To detect cold antibodies, the following rules should be observed when sampling blood for sampling:

Cold agglutinin disease .At the primary intra-vascular hemolysis in a titer of 1: 1000 and above, monoclonal antibodies( usually with kappa-chains) are determined to 1-antigen of erythrocytes. These antibodies are active in a wide range of temperatures, including the temperature of the skin of the extremities( 30-32 ° C).The disease proceeds chronically due to periodic exacerbations caused by winter hypothermia. It is more common in older women( Raynaud's syndrome).Exacerbation is accompanied by typical symptoms of intravascular hemolysis: fever, back pain, severe weakness, shortness of breath and hematuria. Can be splenomegaly. The levels of hemoglobin and hematocrit are reduced. Occasionally, spherocytes and phagocytized erythrocytes are found in blood smears;polychlorochromia. The serum contains cold agglutinins. It is characteristic that at room temperature the agglutination of erythrocytes is so pronounced that it is impossible to calculate them. Direct Coombs test with antibodies to immunoglobulins is usually negative, with antibodies to complement - can be positive.

Secondary intravascular hemolysis usually reveals cold polyclonal antibodies( low titer) active in a narrow temperature range, and they appear more often than hemolysis. In infectious patients( mycoplasma and some viral infections), cold agglutinins are detected to 1-antigen of erythrocytes, with infectious mononucleosis and hemoblastoses - to the i-antigen. With a control sample in practically healthy people, cold antibodies are found in a titer of no more than 1:64;they are usually polyclonal and directed against 1-antigen of erythrocytes.

In the treatment of autoimmune hemolytic anemia with Cold agglutinins, immunosuppressive therapy produces a non-permanent and partial effect. Therefore, plasmapheresis is often used.

Paroxysmal cold hemoglobinuria( Donat-LandSpainper syndrome) is a rare form of autoimmune hemolytic anemia with Cold antibodies. Hemolysis in this disease occurs as a result of a two-phase reaction involving IgG, which is called the antibodies of Donat-Landsteiner. In the first phase, IgG binds to erythrocytes at a low temperature and fixes complement. In the second phase, at a temperature of 37 ° C, complement activation occurs leading to hemolysis. The antibodies of Donat-Landsteiner have an affinity for the ß-antigen of erythrocytes.

Paroxysmal cold hemoglobinuria is rarely primary, and as secondary it is common in patients with syphilis, especially congenital, and complicates viral infections( measles, mumps, chickenpox, infectious mononucleosis, influenza).Intravascular hemolysis develops when the patient warms up after subcooling. The forecast is favorable. Patients usually recover on their own. Occasionally the disease flows for a long time with periodic hemolytic crises.

The diagnosis of the disease confirms the detection of antibodies of Donat-Landsteiner. The procedure involves incubating the patient's serum O( I) mixed with normal red blood cells for 30 minutes.at 4 ° C and at 37 ° C.When the control sample is inactivated, the patient's serum should be incubated with healthy red blood cells first at 37 ° C, then at 4 ° C.

The agent of choice for the treatment of autoimmune hemolytic anemia are glucocorticoid hormones, which practically always stop or reduce hemolysis. A necessary condition for hormone therapy is a sufficient dosage and duration of treatment. In the acute phase prednisolone is prescribed in large doses - 60-80 mg / day( at the rate of 1 mg / kg body weight) or equivalent doses of other glucocorticoids. After the onset of remission, the dose of prednisolone gradually decreases. The maintenance dose is 5-10 mg / day. Treatment is carried out for 2-3 months, until all signs of hemolysis and negativity of the Coombs sample disappear. In some patients, the effect is provided by immunosuppressants( 6-mer-captopurine, azathioprine, chlorambucil), as well as antimalarial drugs( delagil, resichin).Particularly pronounced effect of immunosuppressants is in autoimmune hemolytic anemia associated with Cold agglutinins. The dose of 6-mercaptopurine and azathioprine is 100-150 mg / day, chlorambucil is prescribed in a dose of 10-15 mg. With relapsing forms of the disease and the absence of the effect of the use of glucocorticoids and immunosuppressants, splenectomy is shown. Blood transfusion in patients with autoimmune hemolytic anemia should be carried out only for vital indications( a sharp drop in hemoglobin, a co-morbid state).It is recommended to select the donors, whose erythrocytes give a negative Coombs test.

Disease of Marijafa-Micheli. Hemolytic anemia with persistent hemosiderinuria and paroxysmal nocturnal hemoglobinuria, caused by a change in the structure of the erythrocyte membrane( Marciafawa-Mikeli's disease) is an acquired hemolytic anemia with persistent intravascular hemolysis and excretion in the urine of hemosiderin.

Disease occurs as a result of somatic mutation of erythroid cells, resulting in a pathological clone of erythrocytes with increased sensitivity to various hemolytic agents. The intensity of hemolysis increases with the development of acidosis, as well as under the influence of properdin, complement and thrombin. Morphological feature of the disease is hemosiderosis of the kidneys. Hemosiderosis in other organs is not observed. In the liver, dystrophic and necrobiotic changes associated with venous thrombosis and anemia are noted. The spleen is enlarged, due to multiple vascular thromboses and the development of perivascular sclerosis.

Patients complain of weakness, dizziness, shortness of breath, palpitations, abdominal pain of varying localization and intensity. All this is associated with hemolytic crisis and capillary thrombosis of mesenteric vessels. Often there are thromboses of peripheral vessels, more often veins of upper and lower extremities, as well as other vessels( cerebral, splenic, renal).During the crisis, patients may have fever. In connection with hemoglobinuria and hemosiderinemia, urine is colored black. Often, hemoglobinuria occurs at night, which is explained by physiological acidosis during sleep, activation of properdin and other factors that enhance hemolysis. Hemoglobinuria is not a mandatory symptom of the disease. At objective research mark pallor of a skin with a small icteric shade, moderate increase in a spleen and a liver.

Anemia has a normochromic character for a long time. With significant loss of iron, the color index becomes below the norm. The amount of reticulocytes increased slightly. Often there is leukopenia and thrombotic cytopenia. In the bone marrow - hyperplasia of the erythroid sprout is often accompanied by depression of the granulocyte and megakaryocyte sprouts. Markiafawa-Micheli's disease should be differentiated from hemolytic anemia, resistant to treatment, accompanied by leukemia and thrombocytopenia without significant increase in the spleen. An important diagnostic value is the microscopy of the sediment on hemosiderinuria. Among the laboratory tests in the diagnosis of Marciafava-Mikeli disease, the acid test of hem( hemolysis of erythrocytes of a patient in acidified serum of a healthy person), the Crosby test( increase of hemolysis due to thrombin) and the sucrose test( hemolysis of erythrocytes in patients with fresh donor blood with the addition of sucrose) are important.

An effective method of treatment of Marietaafa-Mikeli disease is the transfusion of three times washed with a physiological solution of sodium chloride erythrocytes. Such red blood cells are poured once in 4-5 days, in an amount of 200-400 ml not later than 48 hours after the capture. For the prevention and treatment of thrombosis, anticoagulant therapy is indicated. During the hemolytic crisis, a slight decrease in hemolysis is achieved with the introduction of plasma substitutes, in particular dextran or polyglucin in an amount of 500-1000 ml. Glucocorticoids and iron preparations are contraindicated in the Marciafava-Mikeli disease.

Drug immune hemolytic anemia accounts for about 20% of all acquired immune hemolytic anemia. An important role in the pathogenesis of the disease is played by:

The first and most important stage of treatment of drug immune hemolytic anemia is the withdrawal of the drug that caused it. When hemolysis caused by immune complexes, then quickly recover. In hemolysis caused by autoantibodies, the recovery is slower( usually several weeks).The Coombs test can remain positive for 1-2 years.

Hemolytic disease of the newborn usually develops when the mother and fetus are incompatible with the Rh-factor and the ABO system, much less often with Kell, Duffy and MNSs antigens. This includes iso-immune hemolytic anemia, i.e.diseases caused by exposure to isoimmune antibodies( hemolytic anemia associated with Rh-incompatibility or incompatibility in the AVO group between mother and fetus) and post-transfusion anemias due to incompatibility with group or Rh-accessory.

Hemolytic disease of newborns, caused by incompatibility with antigens of the Rh system. The development of antibodies to antigens of the Rh system, in contrast to antibodies to antigens of the ABO system, occurs only when this antigen enters the mother's blood. With a normal pregnancy, the number of red blood cells that enter the mother's blood is too low, and there is no immunization. A sufficient amount of fetal blood for immunization can get into the mother's blood in the third stage of childbirth. In the first pregnancy, hemolytic disease of the newborns, caused by incompatibility with Rh system antigens, occurs only if the mothers used to transfuse blood incompatible with the Rh system antigens, or the mother was immunized with amniocentesis. In contrast, with incompatibility with ABO system antigens, hemolytic disease of newborns can occur even during the first pregnancy, because antibodies to these antigens are constantly present in the mother's blood. Most often, with hemolytic disease of newborns, due to incompatibility with the antigens of the Rh system, antibodies to the D-antigen are produced. This antigen is absent in about 15% of whites and 7% of blacks.

The fetus develops hemolytic anemia, which in severe cases leads to heart failure, dropsy and death. Hyperbilirubinemia does not occur in the fetus, as bilirubin freely penetrates the placenta and enters the mother's blood. In a newborn, on the other hand, the greatest danger is hyperbilirubinemia, since it can lead to bilirubin encephalopathy. Sometimes hepatosplenomegaly is observed. Differential diagnosis is carried out with hepatitis, infections, metabolic diseases and hemorrhagic neonatal disease.

In the early stages of pregnancy, determine the group( according to the ABO and Rh systems) blood accessory of a pregnant woman and examine her serum for antibodies to rare erythrocyte antigens. If the mother Rh is negative, determine the Rh-belonging of the child's father. During pregnancy, the titre of antiresusive antibodies is regularly determined. When anti-rhesus antibodies appear, the intensity of hemolysis is evaluated. To do this, spectrophotometric analysis of the amniotic fluid obtained by amniocentesis is carried out. When incompatible with the antigens of the Rh system, the levels of hemoglobin and bilirubin in the cord blood immediately after birth are determined. Conduct a direct sample of Coombs with the red blood cells of the newborn. When a positive sample is determined, to which erythrocyte antigens are directed antibodies. If in the maternal blood antibodies to these antigens are absent, find out why the direct test of Coombs is positive.

Intensive early treatment reduces the risk of complications. Treatment should begin in the intrauterine period. If the titer of antiresusive antibodies in the mother exceeds 1: 8, amniocentesis is performed. To indirectly determine the level of bilirubin and assess the severity of hemolysis, measure the optical density of amniotic fluid at a wavelength of 450 nm. High optical density of amniotic fluid in the middle and late pregnancy is evidence of severe hemolysis in the fetus. In this case, it is necessary to conduct a general analysis of fetal blood. It is obtained by cordocentesis. Reduction of hematocrit up to 18% and less serves as an indication for intrauterine transfusion of erythrocyte mass of Rh-negative blood of group 0( I).If necessary, transfusion of erythrocyte mass is repeated every 2-3 weeks. Repeated transfusions of erythrocyte mass can partially or completely suppress erythropoiesis in the fetus. If fetal development corresponds to gestational age, a cesarean section is performed at the 33-36th week of pregnancy. Immediately after the birth of a child, determine his blood group and conduct a direct test of Coombs. After intrauterine transfusion of erythrocyte mass, the blood of a newborn can become Rh-negative. If a direct test of Coombs in a newborn is positive, an exchange transfusion may be required. Treatment of a newborn child: with hyperbilirubinemia, light therapy and exchange blood transfusion are used. For light therapy, blue light is used that promotes the conversion of bilirubin into water-soluble products. Light therapy is used in addition to exchange blood transfusion - before and after it. Light therapy should not replace diagnostic measures aimed at finding out the causes of jaundice. During the treatment of light it is necessary to regularly determine the level of bilirbin in the serum, because the intensity of jaundice in newborns does not correspond to the severity of hemolysis. To prevent damage to the retina during light therapy, the child's eyes are closed with a bandage. In case of anemia( hemoglobin level below 70-100 g / l), red blood cell transfusion may be required. Erythrocytes coated with anti-rhesus antibodies are sometimes destroyed slowly, which can lead to anemia in the absence of hyperbilirubinemia 3-6 weeks after birth.

Hemolytic disease of newborns, caused by the incompatibility of antigens of the ABO system, usually occurs in children with blood group A or B, born to mothers with blood group 0( I).In the serum of the mother with the blood group 0( I), isogemagglutinins are present to the erythrocyte antigens A and B. It is impossible to predict the development of the hemolytic disease of the newborn by the titer of these antibodies in the mother.

Hemolytic disease can occur even in a child born from the first pregnancy. In term infants, severe anemia and dropsy are rare. Sometimes jaundice appears in the first day of life, however hemolysis is much less pronounced than with incompatibility with the Rh system antigens.

Differential diagnosis of the disease is justified by the exclusion of other causes of hyperbilirubinemia and the detection in the blood smear of newborn spherocytes, and sometimes - of fragmented erythrocytes.

Hemolytic disease of newborns, caused by incompatibility with antigens of the ABO system, can be difficult to distinguish from hereditary microspherocytosis. Direct Coombs test with newborn erythrocytes is usually negative or weakly positive, as they carry a small amount of antigens A and B, and the sensitivity of the sample is not high. Antibodies washed off from the erythrocytes of a newborn are associated with adult erythrocytes with blood groups A, B and AB.

Treatment is aimed at reducing hyperbilirubinemia. Light therapy reduces the need for blood-substitution therapy, which is currently carried out only in 1 out of 3,000 newborns with hemolytic disease caused by an incompatibility with antigens of the ABO system. If a blood transfusion is nevertheless required, a erythrocyte mass of the 0( I) group with a low titer of antibodies to antigens A and B is used.

Erythroblastosis - a hemolytic disease of the newborns can arise during pregnancy of the Rh-negative mother by a Rh-positive fetus when the mother begins to developantibodies that cause agglutination of the fetal erythrocytes. Particular danger in this regard is repeated pregnancy, when the mother's blood already has antibodies after the previous pregnancies.

This group of anemia combines hemolytic states in which the full-fledged erythrocytes are destroyed due to hyperreactivity of RES or under the influence of hemolytic( phenylhydrazium, lead, benzene, arsenic hydrogen, aniline dyes, snake and fungal poisons, etc.), bacterial( toxins of hemolytic streptococcus, staphylococcus, etc.), parasitic( malaria) and other factors. The pathogenesis of these anemias is different: destruction of the erythrocyte membrane, depletion of their enzyme systems, etc.

Hyperplenism, congestive splenomegaly is a condition in which the spleen increases with its phagocytic function. In this case, pancytopenia is observed, and the sequestration of erythrocytes is due to the mechanical "sieve effect".The volume of plasma increases - hemodelation. The production of spleen antibodies aggravates the situation due to the autoimmune factor.

The degree of anemia is directly related to the size of the spleen: an increase in the spleen by 2 cm beyond the edge of the costal arch approximately corresponds to a decrease in the amount of hemoglobin by 1 g. The value of the hematocrit corresponds to the value of hemodilution. Specific changes in the morphology of erythrocytes in the smears of peripheral blood are absent. The lifetime of red blood cells is shortened.

Therapy is aimed at the underlying disease that caused hypersplenism. Splenectomy, as a rule, is not indicated.

Anemia as a consequence of mechanical damage to erythrocytes. With excessive deformation or under the influence of turbulence in the smears of peripheral blood, fragments of erythrocytes( schizocytes, helmet-shaped cells) appear, which are the main criterion for the diagnosis of anemia. The cause of erythrocyte destruction may be outside the vessels( march hemoglobinuria), in the heart( calcification and stenosis of the aortic valve or defects of its prosthesis), in arterioles( malignant hypertension, malignant tumor) and inside vessels( disseminated intravascular coagulation).Sometimes hemolysis is complicated by iron deficiency anemia as a result of chronic hemosiderinuria. Therapy is aimed at the underlying disease, the use of iron preparations is indicated.

Hemolysis caused by the action of bacterial hemolysins. Hemolysis of erythrocytes can be associated with the cytotoxicity of extracellular bacterial hemolysins, for example, streptococci, staphylococci, Haemophilus ducreyi or Clostridium perfringens.

These exotoxins, acting directly on the cell membrane, cause lysis of erythrocytes, platelets and macrophages. For example, hemolysin Clostridium perfringens, a thermolabile protein whose hemolytic and lethal activity increases after treatment with cysteine ​​and is equally dramatically lost by oxygen, lysing red blood cells in the vascular bed. The intravenous administration of 10-18 μg of hemolysin to rabbits leads to their death within 2 to 24 hours. The clinical picture of diseases is mainly determined by the nature of the infectious process. Common symptoms are weakness, lethargy, poor appetite, a temperature reaction, pallor of the skin and mucous membranes. In blood smears - signs of normo- or hypochromic anemia, anisocytosis;the amount of reticulocytes is not increased. The bone marrow picture is not pathognomonic. Sometimes the erythroid sprout is reduced, the erythron is ripening. The level of iron in the serum is reduced. The developing anemia is symptomatic and stops with effective antibiotic therapy. When hypochromia, iron preparations are used. The prognosis of the disease after the eradication of the infectious process is favorable in most cases.

Anemias associated with exposure to direct hemolysins and other damaging factors. The cause of acute massive intravascular disruption of erythrocytes with excretion of hemoglobin in the urine can be various obligate and facultative factors: poisoning with acetic essence, ingestion of snake, mushroom, fish poison. The clinical picture is characterized by a sharp pallor of the skin without pronounced jaundice. The spleen, as a rule, does not increase. There is moderate hepatomegaly. Urine of dark color, the color of black beer or a strong solution of potassium permanganate. Moderate bilirubinemia due to the indirect fraction, a positive test of Ham and a sucrose test, hypersideremia. In blood smears, signs of severe anemia, reticulocytosis, sometimes leukemoid reaction;The current is sharp. Distinguish between severe, moderate and mild forms of the disease.

The diagnosis is based on the clinical-haematological picture and the characteristic color of urine. The prognosis is often favorable, but relapses are possible.

In therapy, corticosteroid hormones( prednisolone up to 1.5-2.0 mg / kg), anabolic steroids, and transfusion of washed-up erythrocytes are used. Preparations of iron, vitamin B12 and whole blood transfusion are contraindicated. Splenectomy is ineffective.