Hemolytic anemia: forms of the disease. Symptoms and signs of the disease in adults and children

Hemolytic anemia

Anemia, in which the process of destruction of red blood cells prevails over the process of regeneration, is called hemolytic.

Natural death of an erythrocyte (erythrodierez) occurs 90-120 days after its birth in the vascular spaces of the reticulohistiocytic system, mainly in the sinusoids of the spleen and much less often directly in the bloodstream. With hemolytic anemia, premature destruction (hemolysis) of red blood cells is observed. The resistance of the erythrocyte to various influences of the internal environment is due to both the structural proteins of the cell membrane (spectrin, ankyrin, protein 4.1, etc.) and its enzyme composition, in addition, normal hemoglobin and the physiological properties of blood and other environments in which the erythrocyte circulates . When the properties of an erythrocyte are disrupted or its environment changes, it is prematurely destroyed in the bloodstream or in the reticulohistiocytic system of various organs, primarily the spleen.

Hemolytic anemias are heterogeneous in their pathogenesis, so establishing the mechanism of hemolysis is an important clinical task that is not always easy to solve.

Classification.

Usually, hereditary and acquired hemolytic anemias are distinguished, since they have different mechanisms of development and differ in approach to treatment. Less commonly, hemolytic anemias are classified according to the presence or absence of immunopathology, distinguishing between autoimmune and nonimmune hemolytic anemias, which include congenital hemolytic anemias, acquired hemolytic anemias in patients with liver cirrhosis, as well as in the presence of prosthetic heart valves and the so-called march hemoglobinuria.

Hemolytic anemias have a number of characteristics that distinguish them from anemias of other origins. First of all, these are hyperregenerative anemias, occurring with hemolytic jaundice and splenomegaly. High reticulocytosis in hemolytic anemia is due to the fact that during the breakdown of erythrocytes, all the necessary elements for the construction of a new erythrocyte are formed and, as a rule, there is no deficiency of erythropoietin, vitamin B12, folic acid and iron. The destruction of red blood cells is accompanied by an increase in the content of free bilirubin in the blood; when its level exceeds 25 µmol/l, hysteria of the sclera and skin appears. Enlargement of the spleen (splenomegaly) is the result of hyperplasia of its reticulohistiocytic tissue, caused by increased hemolysis of red blood cells. There is no generally accepted classification of hemolytic anemia.

Hereditary hemolytic anemia.

A. Membranopathy due to disruption of the structure of the erythrocyte membrane protein:

Microspherocytosis; elliptocytosis; stomatocytosis; piropoikilocytosis

Disorders of erythrocyte membrane lipids: acanthocytosis, deficiency of lecithin-cholesterol acyltransferase activity, increased lecithin content in the erythrocyte membrane, infantile pycnocytosis

B. Enzymepathies:

Pentose phosphate cycle enzyme deficiency

Shortage enzyme activity glycolysis

Deficiency of glutathione metabolic enzyme activity

Deficiency in the activity of enzymes involved in the use of ATP

Ribophosphate pyrophosphate kinase activity deficiency

Impaired activity of enzymes involved in the synthesis of porphyrins

B. Hemoglobinopathies:

Caused by an anomaly in the primary structure of hemoglobin

Caused by a decrease in the synthesis of polypeptide chains that make up normal hemoglobin

Caused by a double heterozygous state

Hemoglobin abnormalities not accompanied by the development of the disease

Acquired hemolytic anemia

A. Immune hemolytic anemia:

Hemolytic anemias associated with exposure to antibodies: isoimmune, heteroimmune, transimmune

Autoimmune hemolytic anemia: with incomplete warm agglutinins, with warm hemolysins, with complete cold agglutinins, associated with biphasic cold hemolysins

Autoimmune hemolytic anemia with antibodies against normocyte antigen bone marrow

B. Hemolytic anemia associated with membrane changes caused by somatic mutation: PNH

B. Hemolytic anemia associated with mechanical damage to the erythrocyte membrane

D. Hemolytic anemia associated with chemical damage to red blood cells (lead, acids, poisons, alcohol)

D. Hemolytic anemia due to deficiency of vitamins E and A

At the stage of a clinical blood test, a laboratory doctor examines the morphology of red blood cells. At the same time, various changes can be detected: micro-sphero-, oval-, ellipto-, stomato-, acantho-, pyropycnocytosis, target-shaped erythrocytes, which gives reason to assume one of the variants of membranopathy, and target-shaped erythrocytes are characteristic of thalassemia. If there are Heinz-Ehrlich bodies in erythrocytes against the background of anisopoikilocytosis, one of the variants of hereditary fermentopathy can be assumed. For sickle cell hemolytic anemia, a metabisulfite test or a test with a sealed drop of blood is performed, which increases the number of sickle red blood cells and thereby facilitates diagnosis. Intravascular hemolysis is manifested by the presence of fragmented red blood cells, the number of which sometimes reaches 100%, which is observed in disseminated intravascular coagulation syndrome, which accompanies many serious diseases, as well as in case of poisoning with hemolytic poisons, marching hemolysis and with an artificial heart valve. Thus, the altered morphology of erythrocytes, characteristic of certain variants of hemolytic anemia, allows us to justify further diagnostic search.

Already at the first acquaintance with a patient with anemia, it is advisable to find out whether he belongs to one or another ethnic group, since it is known that Azerbaijanis, residents of Dagestan, Georgians and Mountain Jews are more likely to suffer from hereditary hemolytic anemia. You should ask the patient if there is any blood relatives patients with anemia, when the first symptoms of anemia appeared, when anemia was first diagnosed. The hereditary nature of hemolytic anemia is sometimes indicated by the presence of cholelithiasis diagnosed in the patient or his relatives at a young age (hyperbilirubinemia can contribute to stone formation in gallbladder and ducts).

At physical examination In patients with hereditary hemolytic anemia, in some cases changes in the bone skeleton and skull structure are detected. The totality of medical history, physical and laboratory research allows you to determine the hemolytic nature of anemia. Further research is aimed at clarifying the main pathogenetic link of hemolytic anemia.

There are clinical and laboratory differences between intravascular and intracellular hemolysis. Thus, when red blood cells are destroyed in the spleen, liver, and bone marrow, heme catabolism occurs in macrophages: under the influence of the enzyme heme oxygenase, verdohemoglobin is formed, iron is cleaved off, then biliverdin is formed, which, under the influence of biliverdin reductase, is converted into bilirubin. Once in the general bloodstream, bilirubin binds to albumin; in the liver, albumin is cleaved off, and bilirubin combines with glucuronic acid, forming bilirubin mono- and diglucuronide, which enter the bile and are released into the intestines. There, under the influence of microflora, it turns into urobilinogen, and then into stercobilin. This process is similar to the physiological one: approximately 1% of red blood cells die daily, mainly in the reticulohistiocytic system of the spleen, liver, and bone marrow. But with hemolytic anemia, hemolysis increases sharply, therefore, the content of free bilirubin in the blood increases, its excretion into bile increases, violating its colloidal stability, and preconditions are created for the development of cholelithiasis.

Some red blood cells are destroyed in the bloodstream and are normal. In this case, free hemoglobin binds to plasma proteins: haptoglobin, hemopexin, albumin. The resulting complexes are captured by hepatocytes and then removed by cells of the reticulohistiocytic system. If the destruction of red blood cells occurs directly in the bloodstream, and the amount of free bilirubin exceeds the hemoglobin-binding capacity of haptoglobin, then free hemoglobin penetrates from the blood into the urine through the glomerular barrier of the kidneys: hemoglobinuria occurs, and the urine becomes dark in color.

A valuable indicator of hemolysis is the level of haptoglobin: the more intense the hemolysis, the more haptoglobin is consumed; at the same time, its consumption exceeds the synthetic capacity of the liver (haptoglobin is synthesized in the liver and belongs to the class of a 2 -globulins), and therefore the level of haptoglobin sharply decreases, which is observed primarily with intravascular hemolysis.

Thus, clinical and laboratory signs characteristic of intracellular hemolysis, are: yellowness of the skin and sclera, splenomegaly, increased free bilirubin, decreased haptoglobin levels. For intravascular hemolysis an enlarged spleen is uncharacteristic; thrombosis is observed in various organs, pain appears in various localizations (in the kidneys, heart, abdominal cavity) due to the development of heart attacks; the icterus of the sclera and skin is weakly expressed; the level of free hemoglobin in the blood serum is sharply increased, and haptoglobin, on the contrary, is sharply decreased; free hemoglobin is determined in the urine, and after a few days - hemosiderin; symptoms of intoxication are expressed (chills, fever).

Thus, analysis of clinical and laboratory data helps to distinguish between intracellular and intravascular hemolysis and come closer to determining the variant of hemolytic anemia. Thus, intracellular hemolysis is more characteristic of membranopathies, and high-quality hemoglobinopathies and acquired autoimmune hemolytic anemias occur with intravascular hemolysis.

Hemolytic anemias occupy 11.5% of the anemia structure, i.e. are much less common than iron deficiency anemia. Some forms of hemolytic anemia are common in people of certain ethnic groups. However, given the significant migration of the population, the doctor may encounter a form of hemolytic anemia that is not typical for the population of Ukraine.

Microspherocytic hemolytic anemia.

The disease is widespread; its frequency in the population is 1:5000. Hereditary microspherocytosis is transmitted by an autosomal dominant type, less often - by an autosomal recessive type; 25% of cases are sporadic due to a new mutation. The disease was first described in 1871. Minkowski (1900) and Shoffar (1907) identified it as an independent nosological form and established its hereditary nature.

Pathogenesis associated with a defect in spectrin, ankyrin, proteins 4.1 and 4.2, with their deficiency or absence. This leads to the fact that the erythrocyte membrane takes on the appearance of a mesh, through the openings of which many active substances necessary to ensure the stability of the membrane freely enter and exit. In this case, electrolyte metabolism is disrupted, since sodium and water penetrate into the erythrocyte in increased quantities, as a result of which the erythrocyte swells, becomes larger, and acquires spherical shape. Subsequently, the size of the erythrocyte decreases as it passes (passage) through the sinusoids of the spleen, its membrane is “trimmed” from the surface, and the erythrocyte decreases in size (microcytosis), maintaining a spherical shape.

Clinic. An objective examination reveals skull deformation, polydactyly, and a high, “Gothic” palate. These changes are due to the expansion of the bridgehead of hematopoiesis, which moves during the period of growth from flat bones to tubular ones. The skin and visible mucous membranes are jaundiced to varying degrees, which depends on the phase of the disease: hemolytic crisis or remission. The spleen and sometimes the liver are enlarged; cholelithiasis and attacks of biliary colic are common.

Picture of blood. The anemia is normochromic. The hemoglobin concentration outside of a hemolytic crisis remains at the level of 90-100 g/l, and during a crisis it decreases to 40-50 g/l. Red blood cells are small in size, have a spherical shape, and the central clearing is not detected (microspherocytosis). The number of reticulocytes is increased both during the period of remission and (especially) after a hemolytic crisis - 10-15 and 50-60%, respectively. The platelet count remains normal; the number of leukocytes increases during a crisis, sometimes a nuclear shift to juvenile forms is observed; ESR is increased due to a decrease in the amount of red blood cells. The osmotic resistance (persistence) of red blood cells is reduced: their hemolysis begins already in a 0.78% sodium chloride solution. In doubtful cases, it is recommended to pre-incubate red blood cells for 24 hours, after which their fragility increases. It is possible to study the spontaneous lysis of erythrocytes after two-day incubation under sterile conditions: if normally 0.4 to 5% of erythrocytes are destroyed, then with microspherocytic anemia - 30-40%. If glucose is added to red blood cells, then their autolysis in a healthy person is reduced to 0.03-0.4%, and in patients with microspherocytic hemolytic anemia - to 10%. At the same time, microspherocytes are more stable in an acidic environment than normal erythrocytes.

IN biochemical blood test most often the content of free bilirubin is increased, but not always. So, if the functional capacity of the liver is preserved, and hemolysis is small, then due to the binding of bilirubin with glucuronic acid, a normal level of free and bound bilirubin is ensured. The concentration of free bilirubin naturally increases after hemolytic crisis, which can develop after an accidental infection; under these conditions, massive breakdown of red blood cells is observed and the liver “does not have time” to bind free bilirubin with glucuronic acid to form conjugated bilirubin. Hemolysis may be accompanied by obstructive jaundice caused by the formation of pigmented gallstones in bile ducts; in these cases, the content of both fractions of bilirubin increases; the content of urobilinogen increases in urine, and stercobilin in feces. The hemolytic crisis is accompanied by activation of erythropoiesis: in the bone marrow aspirate there is a pronounced normoblastic reaction. Individual cases of aplastic hemolytic crisis are described, when there is no response activation of erythropoiesis, and the number of erythroid germ cells in the bone marrow is reduced. More often, this condition is observed against the background of a developed infection.

The course of microspherocytosis in homozygotes is usually severe and manifests itself from childhood, while in heterozygotes it is subclinical and occurs late, sometimes after 20-30 years. Rarer forms of membranopathies have also been described.

Hereditary elliptocytosis inherited in an autosomal dominant manner; its frequency varies from 0.02 to 0.05% in the population among various ethnic groups of the world. During electrophoresis, some patients do not have band 4.1 protein. Red blood cells have the shape of an ellipse, their deformability is reduced, and therefore they are quickly destroyed in the spleen.

The course in the vast majority of cases (95%) is asymptomatic. However, it should be remembered that the presence of elliptocytosis does not always indicate its hereditary nature, since in a healthy person about 15% of red blood cells also have an ellipsoidal shape. Clinically, in manifest cases, jaundice of the skin and sclera, splenomegaly are observed, and cholelithiasis and changes in the bone skeleton are often diagnosed.

Laboratory diagnostics is based on the identification of elliptocytes, which are sometimes rod-shaped. If normally the ratio of mutually perpendicular diameters of the erythrocyte approaches 1, then with elliptocytosis it decreases to 0.78. Target-like erythrocytes may be present, and elliptocytes may vary in size and normochromic coloration. The color index does not deviate from the norm, the hemoglobin level even in homozygotes is not low, varying from 90 to 120 g/l. The number of reticulocytes increases moderately - up to 4%; osmotic resistance of erythrocytes (ORE) is often reduced, but can also be normal; in the latter case, tests are carried out with incubation of erythrocytes and an autolysis test, which reveal a decrease in the RER.

Hereditary stomatocytosis It occurs among people of all ethnic groups with unknown frequency and is inherited in an autosomal dominant manner. The pathogenesis of hemolysis in stomatocytosis is due to an imbalance in the potassium/sodium ratio in the erythrocyte: less potassium accumulates than sodium; the resulting hyperhydration of the erythrocyte reduces the hemoglobin content in it, and when stained, a clearing is formed in the center of the erythrocyte, reminiscent of the outline of a mouth. In some cases, the imbalance between potassium and sodium in the erythrocyte changes and instead of overhydration, dehydration occurs, hemoglobin in the cell “thickens,” and when stained, the erythrocyte takes on a target-like shape. If these cells are placed in a hypotonic solution, they take on the form of a stomatocyte. ORE is usually reduced; red blood cells are destroyed in the spleen, especially in patients with Rh-negative blood. The clinical picture in manifest cases is similar to other hereditary hemolytic anemias. The severity of anemia and jaundice is moderate, splenomegaly develops only with prolonged hemolysis. The concentration of free bilirubin is moderately increased, the hemoglobin level usually does not fall below 90 g/l.

Rarer forms of membranopathies include hereditary acanthocytosis and pyropycnocytosis . Their clinical picture in severe cases is similar to that of other hereditary hemolytic anemias. The main diagnostic test for pyropycnocytosis is a morphological study of red blood cells, which look curved and wrinkled, and in a test with pyrotest (heating to 49-50 ° C), their hemolysis occurs already at a temperature that is 3-4 ° C lower (red blood cells of a healthy person are destroyed only at a temperature of 49-50 ° C) 50 °C).

Acanthocytes got their name due to the presence of numerous outgrowths over their entire surface, which is due to the disproportion in the content of various lipids: in their cell membrane, rigid lecithin predominates over more fluid sphingomyelin. The appearance of acanthocytes is a typical sign of acanthocytosis, but it cannot be considered pathognomonic for this form of anemia, since they can also occur in severe liver pathology, alcoholism, myxedema, and some neurological diseases. The role of heredity in these cases will be evidenced by the presence of hemolytic anemia with moderately elevated levels of reticulocytes and free bilirubin.

Enzymopathies - non-spherocytic hemolytic anemias are caused by a hereditary decrease in the activity of erythrocyte enzymes or their instability. These forms of hemolytic anemia are inherited in an autosomal recessive manner or in an X-linked recessive manner. With them, there are neither morphological changes in erythrocytes nor disturbances in the REM.

Enzymopathies associated with deficiency of G-6-PD activity, common among inhabitants of the Mediterranean coast, among Sephardic Jews, as well as in Africa and Latin America and in former malarial areas Central Asia and Transcaucasia. It is believed that in these geographic regions, natural selection occurred: people with a normal composition of enzymes in the membranes of red blood cells died more often from malaria than people with defective enzyme content, because they were more resistant to the malarial plasmodium. Deficiency of G-6-PD activity among Russians in our country occurs in 2% of cases.

Pathogenesis. Under conditions of G-6-PD deficiency, glutathione metabolism is disrupted, its content in the erythrocyte membrane decreases and hydrogen peroxide accumulates, under the influence of which hemoglobin and membrane proteins are denatured; Heinz-Ehrlich bodies containing denatured hemoglobin appear in red blood cells. Red blood cells are destroyed both in the bloodstream and in the cells of the reticuloendothelial system.

Clinically the disease has a chronic course in the form of non-spherocytic hemolytic anemia, mainly in residents of Northern Europe, less often in the form of acute intravascular hemolysis, most often after taking a provoking drug

paratha with oxidizing properties (antimalarials, sulfonamides), as well as against the background of infection. Symptoms of a crisis: fever, enlarged liver, black urine, sharply colored feces. The spleen remains normal. Option favism characterized by a crisis that develops after eating faba beans or inhaling their pollen. In this case, patients complain of weakness, chills, lower back pain; vomiting appears several hours or days after the action of provoking factors.

Laboratory diagnosis: normochromic, regenerative anemia; anisopoikilocytosis, normocytes, erythrocyte fragments (schizocytes); in erythrocytes - Heinz-Ehrlich bodies. In a biochemical blood test, the content of free bilirubin is increased, and hypohaptoglobulinemia is observed. Bone marrow punctate is characterized by a pronounced normoblastic reaction: up to 50 - 70% of the punctate cells are elements of the red germ. The diagnosis is confirmed after establishing a deficiency of the G-6-PD enzyme in the erythrocyte during the period of compensation of the process in the patient, as well as in his relatives.

Pyruvate kinase activity deficiency as a cause of hemolytic anemia occurs with a frequency of 1:20,000 in the population in all ethnic groups; inherited in an autosomal recessive manner, manifests itself as non-spherocytic hemolytic anemia. In its pathogenesis, blockade of glycolysis with impaired ATP synthesis is important, which leads to a defect in the erythrocyte cell membrane. Hemolysis occurs intracellularly.

Clinic: pallor and yellowness of the skin, splenomegaly. There are both fully compensated and severe forms of the disease. In the hemogram: normochromic anemia, aniso- and poikilocytosis, there may be macrocytes, ovalocytes, acanthocytes, pyropyknocytes. There is no spherocytosis of erythrocytes and Heinz-Ehrlich bodies. The diagnosis is established on the basis of reduced pyruvate kinase activity in the erythrocytes of the patient and his relatives.

Hemoglobinopathies.

This form of hemolytic anemia includes hereditary anomalies of hemoglobin synthesis, caused by a change in the primary structure of its molecule (qualitative hemoglobinopathies) or a violation of the ratio (or synthesis) of one of the globin chains with its unchanged primary structure (quantitative hemoglobinopathies). This is a large group of diseases: more than 500 abnormal hemoglobins (i.e., qualitative hemoglobinopathies) and more than 100 different types of ß-thalassemias, as well as several types of a-thalassemias (i.e., quantitative hemoglobinopathies) have already been identified. According to WHO (1983), about 200 thousand children are born and die annually from hemoglobinopathy of various types, and 240 million heterozygous carriers of hemoglobinopathy, without being sick, may have seriously ill children in their offspring. The distribution of hemoglobinopathies, like other hereditary hemolytic anemias, corresponds to the distribution area of malaria. Among the many hemoglobinopathies there are common ones: thalassemia, sickle cell hemolytic anemia, hemoglobinopathies C, E, D and rare ones - methemoglobinemia, unstable hemoglobins, etc.

Thalassemia - this is target cell anemia with an impaired ratio of HbA and HbF according to biochemical parameters; in this case, partial deficiency of a certain chain or its complete absence is possible with the predominance of another chain. Thus, if synthesis is disrupted, ß-chains will predominate a-chains and vice versa. Beta thalassemia caused by a decrease in the production of hemoglobin ß-chains. Intact a-chains accumulate excessively in erythropoiesis cells, which leads to membrane damage and destruction of both erythroid cells in the bone marrow and erythrocytes in the peripheral blood; Ineffective erythropoiesis and hemolysis develop with hypochromia of erythrocytes, because the hemoglobin content in erythrocytes is insufficient. American pediatricians Cooley and Lee were the first to describe ß-thalassemia in 1925. The severe homozygous form of ß-thalassemia was named Cooley's disease or thalassemia major. In addition, according to the severity of anemia and other clinical symptoms, there are intermediate, small And minimal thalassemia. In addition to the Mediterranean countries, thalassemia is found in France, Yugoslavia, Switzerland, England, Poland, as well as in residents of Transcaucasia and Central Asia, where in some regions the carrier frequency reaches 10-27%.

Pathogenesis of ß-thalassemia associated with a mutation in the ß-globin locus on the 11th pair of chromosomes, disrupting the synthesis of the ß-globin chain. Due to inadequate hemoglobin synthesis, hypochromic anemia develops. Precipitates of excess a-chains are removed from red blood cells and erythrokaryocytes by cells of the reticulohistiocytic system; In this case, the cells are damaged and destroyed faster. This is the mechanism of ineffective erythropoiesis and hemolysis of erythrocytes and reticulocytes; the death of the latter occurs in the spleen. In ß-thalassemia, HbF, which has a high affinity for oxygen, also accumulates; however, its release to tissues is difficult, which leads to their hypoxia. Ineffective erythropoiesis contributes to the expansion of the bridgehead of hematopoiesis, which is reflected in the structure of the skeleton; at the same time, the destruction of erythrokaryocytes in the bone marrow leads to increased absorption of iron and pathological overload of the body with iron. Hematological signs of ß-thalassemia are sometimes detected in anemic Russians.

Thalassemia major clinic appears already in childhood. Sick children have a peculiar tower skull, a Mongoloid face with an enlarged upper jaw. An early sign of Cooley's disease is spleno- and hepatomegaly, developing due to extramedullary hematopoiesis and hemosiderosis. Over time, they develop cirrhosis of the liver, diabetes as a result of pancreatic fibrosis, and myocardial hemosiderosis leads to congestive heart failure.

At blood test Hypochromic hyperregenerative anemia of varying severity is determined. The blood smear reveals small, target-shaped, hypochromic red blood cells of various shapes; many normocytes. A biochemical blood test reveals hyperbilirubinemia due to the free fraction, hypersideremia, a decrease in blood volume, and an increase in LDH activity. The level of fetal hemoglobin in red blood cells is increased.

The definition in the title includes a large group of diseases that differ from each other in their causes, mechanisms of disease development in the body, external manifestations and treatment regimens. The main and common feature for them is the accelerated decay and reduction in life expectancy of red blood cells.

If under normal conditions of existence the lifespan of red blood cells is, as a rule, 100-120 days, then in the presence of hemolytic anemia they are intensively destroyed and their lifespan is reduced to 12-14 days.

The literal destruction of red blood cells (defined as pathological hemolysis) occurs mainly inside the vessels. Inside the cells, the breakdown of red blood cells is possible only in the spleen. The process of intracellular destruction immediately manifests itself by an increase in free bilirubin in the blood serum and an increase in the release of urobilin in excrement. In the future, this may result in stones in the bile ducts and gallbladder.

According to the currently prevailing classification, hemolytic anemias are divided into two groups:

Hereditary;

Purchased.

The two groups differ in that hereditary anemias people receive them as a result of the action of defective genetic factors on the life of red blood cells, and acquired ones develop under the influence of external causes that can destroy initially healthy red blood cells.

Hereditary hemolytic anemias

Minkowski–Choffard disease, or Hereditary microspherocytosis

Named after the researchers who first described it back in 1900. The cause of the disease is a genetic defect in the erythrocyte membrane protein. A defective membrane allows an excessive amount of sodium ions into the red blood cell and contributes to the accumulation of water in it. As a result, spherocytes are formed. Spherocytes, or spherical red blood cells, are not able to squeeze through the narrow lumens of the bloodstream, for example, when passing into the sinuses of the spleen, which leads to stagnation of the movement of red blood cells, from which particles of their surface are split off, and from them, in turn, microspherocytes are formed. By the way, this is where the name of the disease comes from – microspherocytosis. Destroyed red blood cells are utilized by macrophages of the spleen.

The process of constant hemolysis of red blood cells in the spleen forces it to grow and build up pulp in order to cope with the situation. Therefore, the organ noticeably increases in size over time, usually protruding from under the hypochondrium by 2-3 cm. The breakdown of red blood cells in the serum promotes the growth of free bilirubin in the blood, from where it enters the intestines and is excreted from the body natural ways in the form of stercobilin, the daily amount of which for this disease is twenty times higher than the norm.

Clinical picture

The external manifestations of the disease depend on the severity of the process of destruction of red blood cells. Most often, the first symptoms of the disease are detected in adolescence, and in children it is usually discovered during examination of their relatives about the disease.

Outside of the exacerbation of the process, complaints may be absent; as the situation worsens, the patient begins to complain of weakness, dizziness, and fever. For a doctor the main clinical symptom serves as jaundice, which long time may remain the only one external manifestation diseases. The intensity of jaundice depends on two factors: the rate of hemolysis and the ability of the liver to process the continuously supplied free bilirubin. Therefore, the healthier the liver is initially, the less pronounced the jaundice.

A laboratory test of urine does not find free bilirubin in it. The stool is an intense dark brown color. The tendency to stone formation characteristic of the disease can provoke an attack of hepatic colic. With mechanical blockage of the common bile duct, a picture of obstructive jaundice develops: skin itching, bile pigments in the urine, etc.

The liver, during a quiet course of the disease without complications, is usually of normal size, only occasionally in patients for a long time suffering from hemolytic anemia, its increase is noted. Children show symptoms of delayed development. Changes in the facial skeleton like a tower skull, the formation of a saddle nose, narrow eye sockets, high palate and dental malocclusion are also noted.

Each patient has a different severity of the disease. If some patients often experience a slight decrease in the amount of hemoglobin, then in other patients there is no anemia at all. In old age, trophic ulcers of the leg that are difficult to treat are sometimes encountered, which is associated with hemolysis of red blood cells in the small capillaries of the lower extremities.

The disease occurs with characteristic hemolytic crises, which are expressed in a sharp increase in normal symptoms. As complaints grow, the patient’s body temperature rises, caused by increased breakdown of red blood cells, the intensity of jaundice increases, and severe pain in the stomach and vomiting. Hemolytic crises are usually triggered by third-party infection, hypothermia, and in women they develop in connection with pregnancy. The frequency of crises is strictly individual; for some, they are absent altogether.

Diagnosis

For a doctor, the diagnosis of hereditary microspherocytosis is clear if the examined patient has alternating crises and remissions, jaundice, an enlarged spleen (splenomegaly), pain in the right hypochondrium, signs of anemia, confirmed by laboratory blood tests (normochromic anemia, reticulocytosis, microspherocytosis). Additional confirmation of the correctness of the diagnosis can be a number of laboratory tests. For example, the Coombs test helps to establish the correct diagnosis, which detects autoantibodies fixed on red blood cells in hemolytic autoimmune anemia.

A targeted examination by a specialist of close relatives of the sick has important social significance. Moreover, some of them may show subtle signs of destruction of red blood cells, defined by a doctor as microspherocytosis without pronounced clinical manifestations. The probability of developing the disease in children if one of the parents has microspherocytosis is slightly less than 50%.

Treatment

Unfortunately, the only effective way to treat patients with hereditary microspherocytosis is surgical removal spleen – splenectomy. Removal gives almost complete cure, despite the fact that red blood cells retain their pathogenic properties - microspherocytosis and decreased osmotic resistance.

But surgery is not possible for all patients. It is carried out only in the presence of frequent hemolytic crises, splenic infarctions, progressive development of anemia, frequent attacks hepatic colic. If possible, surgeons try to remove the gallbladder along with the spleen. The prognosis for life with hereditary microspherocytosis is favorable: most patients live to old age.

Thalassemia

The concept of thalassemia combines a whole group of hemolytic anemias that are inherited. A common feature for them is a distinct hypochromia of red blood cells (erythrocytes), diagnosed against the background of normal or even increased levels of iron ions in the blood serum. However, quite often patients experience increased bilirubin in the blood and moderate reticulocytosis. The spleen is usually enlarged and easily palpable. Clinical manifestations in a particular patient directly depend on how the disease was inherited: from one of the parents or from both. The overall picture of the disease is also influenced by the type of disruption of one of the four hemoglobin chains.

The reasons for accelerated hemolysis of red blood cells are caused by an altered cell structure, which occurs as a result pathological change the ratio of globin chains within the cell itself. With thalassemia, in addition to shortening the life of red blood cells, bone marrow cells die - erythrokaryocytes, which are responsible for effective blood formation. Erythropoiesis becomes ineffective.

External and internal manifestations thalassemia, transmitted from both parents, develops into a clinical picture of severe hypochromic anemia with pronounced anisocytosis of erythrocytes and the presence of so-called target-like forms of erythrocytes in the blood. “Targets” are formed when, at the site of normal clearing in the center of the erythrocyte, a hemoglobin spot resembling a target is formed. Painful changes occurring in the body are responsible for the formation of a tower skull and saddle nose in the patient, changes in the arrangement of teeth and malocclusion. Early anemia affects the mental and physical development of the child, his skin is usually jaundiced, and his spleen is enlarged. Unfortunately, when severe course Anemic children die before reaching the age of one year. But there are also less severe forms of homozygous thalassemia, which give sick children the opportunity, with proper and timely treatment live to adulthood.

Thalassemia, transmitted from one parent, or heterozygous, can occur with less pronounced deterioration in blood counts. Hypochromic anemia may be moderate, reticulocytosis may be insignificant, and signs of accelerated hemolysis of red blood cells may be absent; the jaundice is only slightly pronounced, and the spleen is slightly enlarged in size.

Diagnosis

The diagnostic sign of thalassemia is normal or elevated levels of iron in the blood serum. Another important test for diagnosis is that in case of iron deficiency anemia, taking iron-containing drugs inevitably leads to an increase in the number of reticulocytes in the blood by the middle of the second week of therapy, and in thalassemia, no matter how much iron the patient consumes, the level of reticulocytes remains unchanged.

The specific form of thalassemia is determined only when special research all four chains of hemoglobin.

Treatment

Treatment of severe homozygous anemia involves attempts to correct the blood picture with red blood cell transfusions. The required amount of blood for transfusion is calculated so as to maintain the hemoglobin level at 85 g/l. Excess iron is removed from the body.

A bone marrow transplant can have a therapeutic effect. Splenectomy is the surgical removal of the spleen, indicated exclusively for severe forms ah hemolysis and catastrophic organ enlargement. But doctors rarely resort to it, trying to fully use bloodless methods of therapy.

Prevention: incest taboo.

Hereditary hemolytic anemia with deficiency of enzyme activity

IN common basis The occurrence of pathology is due to a deficiency in the activity of certain erythrocyte enzymes, as a result of which they (erythrocytes) become painfully sensitive to the effects of various substances plant origin, including medicines. The most common of the non-spherocytic hemolytic anemias is acute hemolytic anemia, caused by a deficiency of a specific enzyme with the complex designation G-6-FDG. Children with its deficiency may develop favism.

Favism- This is an acute hemolytic anemia, characterized by a rapid course. Develops in children with a deficiency of this enzyme when they eat faba beans or inhale pollen from the Vicia Fava plant. The disease was first described more than half a century ago, and then its familial nature was indicated.

Favism occurs mainly in children preschool age, more often in boys. It usually develops rapidly. After inhaling pollen from the Vicia Fava plant, symptoms of the disease appear within a few minutes, and after eating fava beans, symptoms appear within 5-24 hours. Chills, high fever, nausea, vomiting occur, headache, confusion and a state close to collapse are possible. Jaundice gradually increases, the liver and spleen enlarge. Many patients develop hemoglobinuria. The number of red blood cells decreases to 1 x 1012 cells/l within a few days. Sometimes high neutrophilic leukocytosis is determined. The level of indirect bilirubin is increased. The osmotic resistance of erythrocytes is normal or reduced. The Coombs reaction, both direct and indirect, is positive in most patients during the first week of the disease. Acute period usually lasts from two to six days, jaundice lasts somewhat longer. After the restoration of the composition peripheral blood Immunity develops and lasts 6 weeks. Doctors generally give a favorable prognosis for life.

Acute hemolytic, or drug-induced, anemia

Hemolytic crisis can be caused by a variety of reasons. For example, taking even conventional analgesics, sulfonamide and antimalarial drugs, vitamin K, and some chemotherapy drugs such as PAS or furadonin. Eating legumes and legumes can also result in a hemolytic crisis. The severity of the hemolytic process that has occurred directly depends on the amount of the G-6-FDG enzyme and on the dose of the drug or the amount of the product that provoked the crisis. A peculiarity of the reaction is that hemolysis of red blood cells does not occur immediately, but is extended over time, usually for two to three days from the moment of taking provoking drugs.

In severe cases, patients' body temperature rises to the upper limits, severe weakness occurs, severe shortness of breath, palpitations, pain in the abdomen and back, accompanied by profuse vomiting. The patient's condition quickly deteriorates to the point of collapsing. A typical sign of impending collapse is the appearance of dark, even black, urine. This coloring of urine is dictated by the removal from the body of hemosiderin, which is formed as a result of the intravascular breakdown of red blood cells, which, steadily progressing, can result in an attack of acute renal failure. At the same time, yellowness of the skin and visible mucous membranes appears, an enlarged spleen is palpable, and less often the lower edge of the liver can be palpated in the right hypochondrium. As a rule, after a week, the breakdown of red blood cells stops. Hemolysis stops regardless of whether the drug that caused the attack continues to be taken or not.

The diagnosis of acute hemolytic anemia associated with G-6-FDG deficiency is quite simple for a qualified doctor: a clear typical clinical picture in combination with laboratory indicators of acute hemolysis and deficiency in the blood of the said enzyme with a clear connection between the attack and medication use clearly indicates this form of hemolytic anemia. Another confirmation is the identified lack of enzyme in the red blood cells of close relatives.

The main method of treating this type of anemia is quite obvious manipulations: repeated, once or twice a week, transfusions in amounts of up to half a liter of fresh blood of the same group and intravenous infusions large quantities 5% glucose solution or saline solution. To relieve and prevent the development of shock, prednisolone, promedol or morphine are used. Sometimes the use of cordiamine and camphor is required. If the course of the disease is aggravated by acute renal failure, the usual set of therapeutic procedures is carried out. If there is no effect, artificial hemodialysis is inevitable.

To prevent hemolytic crises, you should carefully collect information from the patient. This must be done before introducing medications that can cause worsening. From the outside, taking an anamnesis resembles a confession - the doctor asks, and the patient answers sincerely, thereby helping himself and his attending physician. This is a very important undertaking.

The prognosis for the life and health of a patient with this form of anemia is disappointing if renal failure and anuria develop. Death can occur during the fulminant course of the disease from acute anoxia or shock.

Acquired hemolytic anemia

Autoimmune hemolytic anemia

Among the group of acquired hemolytic anemias, autoimmune hemolytic anemia is the most common. IN medical literature The onset of the development of this disease is usually associated with the appearance in the body of antibodies to its own red blood cells. The body takes up arms against its own red blood cells and “beats” them as if they were strangers due to a breakdown in the “friend or foe” recognition system: the immune system perceives the red blood cell antigen as foreign and begins to produce antibodies to it. After fixation of autoantibodies on erythrocytes, the latter are captured by the cells of the reticulohistiocytic system, where they undergo agglutination and decay. Hemolysis of red blood cells occurs mainly in the spleen, liver, and bone marrow.

There are symptomatic and idiopathic hemolytic autoimmune anemias. Symptomatic autoimmune anemias accompany various diseases associated with disorders of the human immune system. They most often occur when chronic lymphocytic leukemia, lymphogranulomatosis, acute leukemia, with cirrhosis, chronic hepatitis, rheumatoid arthritis, systemic lupus erythematosus.

In cases where doctors are unable to link the formation of autoantibodies with one or another pathological process, it is customary to talk about idiopathic autoimmune hemolytic anemia. Such a diagnosis is made by doctors in approximately half of the cases.

Autoantibodies to red blood cells come in different types. According to the serological principle, autoimmune hemolytic anemias are divided into several forms:

Anemia with incomplete thermal agglutinins;

Anemia with warm hemolysins;

Anemia with complete cold agglutinins;

Anemia with biphasic hemolysins;

Anemia with agglutinins against bone marrow normoblasts.

Each of these forms has its own characteristics in the clinical picture and diagnosis. The most common anemia is with incomplete thermal agglutinins, accounting for up to 4/5 of all cases of autoimmune hemolytic anemia. According to the clinical course, acute and chronic form of this disease.

The acute form is characterized by a sudden onset: severe weakness sets in, the skin quickly turns yellow, the patient develops a fever, is plagued by shortness of breath and attacks of palpitations.

At chronic course The attack of the disease develops slowly and creeps up gradually. In this case, the general condition of the patients changes little, despite the patient’s pronounced anemia. Symptoms such as shortness of breath and palpitations may be absent altogether. The secret here is that with the slow development of the disease, the patient’s body gradually adapts to the condition chronic hypoxia. If desired, you can palpate the edge of the patient’s enlarged spleen, and a little less often, the liver.

In autoimmune anemia associated with cold allergies, which is characterized by poor tolerance to sub-zero temperatures with the development of symptoms of urticaria, Raynaud's syndrome and hemoglobinuria, the course of the disease is characterized by a tendency to exacerbations or hemolytic crises. Deterioration is provoked viral infections coupled with hypothermia. Laboratory blood tests reveal normochromic or moderately hyperchromic anemia varying degrees, reticulocytosis, normocytosis. Cold autoimmune hemolytic anemia is characterized by an agglutination reaction (sticking together) of red blood cells immediately after taking blood and directly in a smear, which disappears when warmed. ESR is greatly increased. The platelet count is unchanged. An increase in the amount of indirect bilirubin is also recorded. The level of stercobilin in the feces is increased.

The diagnosis of autoimmune hemolytic anemia is possible by a combination of two signs: the presence of symptoms of increased hemolysis and the detection of antibodies fixed on the surface of red blood cells. Autoantibodies on red blood cells are detected using the already mentioned Coombs test. There are direct and indirect Coombs tests. A direct test is positive in most cases of autoimmune hemolytic anemia. A negative direct test result means the absence of antibodies on the surface of the red blood cell and does not exclude the presence of free circulating antibodies in the plasma. To detect free antibodies, an indirect Coombs test is used.

Autoimmune hemolytic anemia responds well to treatment with glucocorticoid hormones, which can stop the breakdown of red blood cells in most cases of the disease. After remission occurs, the dose of hormones is gradually reduced. The maintenance dose is 5-10 mg/day. Treatment is carried out for two to three months, until all clinical signs of hemolysis disappear and negative results Coombs tests. In some patients, immunosuppressants (6-mercaptopurine, azathioprine, chlorambucil), as well as antimalarial drugs (delagil, rezoquin), have an effect. In case of recurrent forms of the disease and the absence of effect from the use of glucocorticoids and immunosuppressants, splenectomy is again indicated - removal of the spleen. Blood transfusions in patients with autoimmune hemolytic anemia should be carried out only for health reasons ( sharp drop hemoglobin, loss of consciousness).

1. Hematology / O.A. Rukavitsyn, A.D. Pavlov, E.F. Morshakova [etc.] /ed. O.A. Rukavitsina. – St. Petersburg: LLC “DP”, 2007. – 912 p.

2. Cardiology. Hematology / ed. ON THE. Buna, N.R. College and others - M.: Reed Elsiver LLC, 2009. - 288 p.

3. Visual hematology / Translation from English. Edited by prof. IN AND. Ershova. – 2nd ed. – M.: GEOTAR-Media, 2008. – 116 p.: ill.

4. Papayan A.V., Zhukova L.Yu. Anemia in children: a guide for doctors. – SPb.: PETER. – 2001 – 384 p.

5. Pathophysiology: textbook: in 2 volumes/ed. V.V. Novitsky, E.D. Goldberg, O.I. Urazova. – 4th ed. – GEOTAR-Media, 2010. – T.2. – 848 p.: ill.

6. Pathophysiology: textbook, 3 volumes: [A.I. Volozhin and others]; edited by A.I. Volozhina, G.V. Poryadina. – M.: Publishing Center “Academy”, 2006.- T.2 – 256 pp.: ill.

8. Guide to hematology / Ed. A.I. Vorobyova. - M.: Newdiamed, 2007. - 1275 p.

9. Shiffman F.J. Pathophysiology of blood. – M.: Publishing house BINOM, 2009. – 448 p.

Hemolytic anemia is a group of diseases characterized by pathologically intense destruction of red blood cells, advanced education products of their breakdown, as well as a reactive increase in erythropoiesis. Currently, all hemolytic anemias are usually divided into two main groups: hereditary and acquired.

Hereditary hemolytic anemias, depending on the etiology and pathogenesis, are divided into:

I. Membranopathy of erythrocytes:

a) “protein-dependent”: microspherocytosis; ovalocytosis; stomatocytosis; pyropoikilocytosis; "Rh-zero" disease;

b) “lipid-dependent”: acanthocytosis.

II. Enzymopathies of erythrocytes caused by deficiency:

a) enzymes of the pentose phosphate cycle;

b) glycolysis enzymes;

c) glutathione;

d) enzymes involved in the use of ATP;

e) enzymes involved in the synthesis of porphyrins.

III. Hemoglobinopathies:

a) associated with a violation of the primary structure of globin chains;

b) thalassemia.

Acquired hemolytic anemia:

I. Immunohemolytic anemia:

a) autoimmune;

b) heteroimmune;

c) isoimmune;

d) transimmune.

II. Acquired membranopathies:

a) paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli disease);

b) spur cell anemia.

III. Anemia associated with mechanical damage to red blood cells:

a) march hemoglobinuria;

b) arising from prosthetics of blood vessels or heart valves;

c) Moshkovich disease (microangiopathic hemolytic anemia).

IV. Toxic hemolytic anemia of various etiologies.

Mechanisms of development and hematological characteristics of congenital hemolytic anemias

The above classification of hemolytic anemia convincingly indicates that the most important etiopathogenetic factors in the development of erythrocyte hemolysis are disturbances in the structure and function of erythrocyte membranes, their metabolism, the intensity of glycolytic reactions, pentose phosphate oxidation of glucose, as well as qualitative and quantitative changes in the structure of hemoglobin.

I. Features separate forms erythrocyte membranopathies

As already indicated, pathology can be associated either with a change in the structure of the protein or with a change in the structure of the lipids of the erythrocyte membrane.

The most common protein-dependent membranopathies include the following hemolytic anemias: microspherocytosis (Minkowski-Choffard disease), ovalocytosis, stomatocytosis, more rare forms - piropoikilocytosis, Rh-null disease. Lipid-dependent membranopathies occur in a small percentage among other membranopathies. An example of such hemolytic anemia is acanthocytosis.

Microspherocytic hemolytic anemia (Minkowski-Choffard disease). The disease is inherited in an autosomal dominant manner. The basis for disturbances in microspherocytosis is a reduced content of the actomyosin-like protein spectrin in the erythrocyte membrane, a change in its structure and a disruption of the connection with actin microfilaments and lipids of the inner surface of the erythrocyte membrane.

At the same time, there is a decrease in the amount of cholesterol and phospholipids, as well as a change in their ratio in the erythrocyte membrane.

These violations make cytoplasmic membrane highly permeable to sodium ions. A compensatory increase in the activity of Na, K-ATPase does not ensure sufficient removal of sodium ions from the cell. The latter leads to overhydration of red blood cells and contributes to a change in their shape. Red blood cells become spherocytes, lose their plastic properties and, passing through the sinuses and intersinus spaces of the spleen, are injured, lose part of their membrane and turn into microspherocytes.

The lifespan of microspherocytes is approximately 10 times shorter than that of normal erythrocytes, mechanical resistance is 4-8 times lower, and the osmotic resistance of microspherocytes is also impaired.

Despite the congenital nature of microspherocytic hemolytic anemia, its first manifestations are usually observed in older childhood, adolescence and adulthood, rarely in infants and elderly people.

In patients with microspherocytic anemia, yellowness of the skin and mucous membranes occurs, an enlargement of the spleen, in 50% of patients the liver becomes enlarged, and there is a tendency to form stones in the gall bladder. Some patients may have congenital anomalies of the skeleton and internal organs: tower skull, gothic palate, brady- or polydactyly, strabismus, malformations of the heart and blood vessels (the so-called hemolytic constitution).

Picture of blood. Anemia of varying severity. Reduced number of red blood cells in peripheral blood. The hemoglobin content during hemolytic crises decreases to 40-50 g/l, during the inter-crisis period it is approximately 90-110 g/l. The color index may be normal or slightly reduced.

The number of microspherocytes in peripheral blood varies - from a small percentage to a significant increase in the total number of red blood cells. The content of reticulocytes is persistently increased and ranges from 2-5% during the inter-crisis period to 20% or more (50-60%) after a hemolytic crisis. During a crisis, single erythrokaryocytes may be detected in the peripheral blood.

The number of leukocytes during the inter-crisis period is within the normal range, and against the background of a hemolytic crisis - leukocytosis with a neutrophilic shift to the left. The platelet count is usually normal.

Bone marrow puncture reveals pronounced hyperplasia of the erythroblastic lineage with an increased number of mitoses and signs of accelerated maturation.

With microspherocytic anemia, as with other hemolytic anemias, there is an increase in the level of bilirubin in the blood serum, mainly due to the unconjugated fraction.

Ovalocytic hemolytic anemia (hereditary elliptocytosis). Ovalocytes are a phylogenetically more ancient form of red blood cells. In blood healthy people they are determined in a small percentage - from 8 to 10. In patients with hereditary elliptocytosis, their number can reach 25-75%.

The disease is inherited in an autosomal dominant manner. The pathogenesis is caused by a defect in the erythrocyte membrane, which lacks several fractions of membrane proteins, including spectrin. This is accompanied by a decrease in the osmotic resistance of ovalocytes, an increase in autohemolysis and a shortening of the life span of ovalocytes.

The destruction of ovalocytes occurs in the spleen, so most patients experience its enlargement.

Picture of blood. Anemia of varying severity, most often normochromic. The presence of ovalocytes in the peripheral blood is more than 10-15%, moderate reticulocytosis. Increase in indirect bilirubin in blood serum. Ovalocytosis is often combined with other forms of hemolytic anemia, for example, sickle cell anemia, thalassemia.

Hereditary stomatocytosis. The type of inheritance is autosomal dominant. This is a rare pathology. The diagnosis is based on the detection of a peculiar appearance of red blood cells in a blood smear: an unstained area in the center of the red blood cell is surrounded by colored areas connected at the sides, which resembles an open mouth (Greek stoma). Changes in the shape of erythrocytes are associated with genetic defects in the structure of membrane proteins, which causes increased membrane permeability for Na + and K + ions (the passive penetration of sodium into the cell increases approximately 50 times and the release of potassium from erythrocytes increases 5 times). In most carriers of the anomaly, the disease is not clinically manifested.

Picture of blood. Patients develop anemia, often normochromic. During the hemolytic crisis there is a sharp decline hemoglobin, high reticulocytosis. The level of indirect bilirubin increases in the blood serum.

The osmotic resistance and lifespan of defective red blood cells are reduced.

Determination of an increased amount of sodium ions in altered red blood cells and a decrease in potassium ions is of diagnostic importance.

Acanthocytic hemolytic anemia. The disease belongs to lipid-dependent membranopathies, is inherited in an autosomal recessive manner and manifests itself in early childhood. With this pathology, peculiar red blood cells are found in the blood of patients - acanthocytes (Greek akanta - thorn, thorn). on the surface of such red blood cells there are from 5 to 10 long spike-like projections.

It is believed that in the membranes of acanthocytes there are disturbances in the phospholipid fraction - an increase in the level of sphingomyelin and a decrease in phosphatidylcholine. These changes lead to the formation of defective red blood cells.

At the same time, the amount of cholesterol, phospholipids, triglycerides in the blood serum of such patients is reduced, and β-protein is absent. The disease is also called hereditary abetalipoproteinemia.

Picture of blood. Anemia, often normochromic, reticulocytosis, the presence of red blood cells with characteristic spike-like projections.

The content of indirect bilirubin in the blood serum is increased.

II. Hereditary hemolytic anemia associated with impaired activity of erythrocyte enzymes

Hemolytic anemia associated with deficiency of pentose phosphate cycle enzymes. Insufficiency of glucose-6-phosphate dehydrogenase of erythrocytes is inherited in a sex-linked type (X-chromosomal type). In accordance with this, clinical manifestations of the disease are observed mainly in men who inherited this pathology from their mother with her X chromosome, and in women who are homozygous for the abnormal chromosome. In heterozygous women, clinical manifestations will depend on the ratio of normal red blood cells and red blood cells with glucose-6-phosphate dehydrogenase deficiency.

Currently, more than 250 variants of glucose-6-phosphate dehydrogenase deficiency have been described, of which 23 variants were discovered in the USSR.

The key role of G-6-FDG is its participation in the reduction of NADP and NADPH2, which ensure the regeneration of glutathione in erythrocytes. Reduced glutathione protects red blood cells from decay upon contact with oxidants. In individuals with glucose-6-phosphate dehydrogenase deficiency, oxidants of exogenous and endogenous origin activate lipid peroxidation of erythrocyte membranes, increase the permeability of the erythrocyte membrane, disrupt the ionic balance in cells and reduce the osmotic resistance of erythrocytes. Acute intravascular hemolysis occurs.

More than 40 different types of medicinal substances are known that are oxidizing agents and provoke hemolysis of red blood cells. These include antimalarials, many sulfa drugs and antibiotics, antituberculosis drugs, nitroglycerin, analgesics, antipyretics, vitamins C and K, etc.

Hemolysis can be induced by endogenous intoxications, for example, diabetic acidosis, acidosis in renal failure. Hemolysis occurs during toxicosis of pregnant women.

Picture of blood. A hemolytic crisis provoked by taking a drug is accompanied by the development of normochromic anemia, reticulocytosis, neutrophilic leukocytosis, and sometimes the development of a leukemoid reaction. Reactive erythroblastosis is noted in the bone marrow.

In newborns with a severe deficiency of glucose-6-phosphate dehydrogenase activity, hemolytic crises occur immediately after birth. This is a hemolytic disease of newborns, not associated with an immunological conflict. The disease occurs with severe neurological symptoms. The pathogenesis of these crises has not been sufficiently studied; it is assumed that hemolysis is provoked by consumption by a pregnant or nursing mother. medicines with hemolytic effect.

Hereditary hemolytic anemia caused by deficiency of erythrocyte pyruvate kinase activity. Congenital hemolytic anemia occurs in individuals homozygous for an autosomal recessive gene. Heterozygous carriers are practically healthy. The enzyme pyruvate kinase is one of the concluding enzymes of glycolysis that ensures the formation of ATP. In patients with pyruvate kinase deficiency, the amount of ATP in erythrocytes decreases and the products of glycolysis of previous stages - phosphophenolpyruvate, 3-phosphoglycerate, 2,3-diphosphoglycerate - accumulate, and the content of pyruvate and lactate decreases.

As a result of a decrease in ATP levels, all energy-dependent processes are disrupted, and primarily the work of Na+, K+-ATPase of the erythrocyte membrane. A decrease in the activity of Na+, K+-ATPase leads to the loss of potassium ions by the cell, a decrease in the content of monovalent ions and dehydration of red blood cells.

Dehydration of red blood cells makes it difficult to oxygenate hemoglobin and release oxygen from hemoglobin to tissues. An increase in 2,3-diphosphoglycerate in erythrocytes partially compensates for this defect, since the affinity of hemoglobin for oxygen decreases when it interacts with 2,3-diphosphoglycerate, and, consequently, the release of oxygen to tissues is facilitated.

Clinical manifestations of the disease are heterogeneous and can manifest as hemolytic and aplastic crises, and in some patients - in the form of mild anemia or even asymptomatic.

Picture of blood. Moderate anemia, often normochromic. Sometimes macrocytosis is detected; the osmotic resistance of erythrocytes is reduced or unchanged; during crises, the content of indirect bilirubin in the plasma increases. The number of reticulocytes in the peripheral blood increases sharply during a crisis, and in some patients erythrokaryocytes appear in the blood.

III. Hemoglobinopathies

This is a group of hemolytic anemias associated with a violation of the structure or synthesis of hemoglobin.

There are hemoglobinopathies caused by an anomaly in the primary structure of hemoglobin, qualitative (sickle cell anemia), and caused by a violation of the synthesis of hemoglobin chains, or quantitative (thalassemia).

Sickle cell anemia. The disease was first described in 1910 by Herrick. In 1956, Itano and Ingram established that the disease is a consequence gene mutation, as a result of which an amino acid substitution occurs in position VI of the β-polypeptide chain of glutamic acid hemoglobin with neutral valine and abnormal hemoglobin S begins to be synthesized, which is accompanied by the development of pronounced poikilocytosis and the appearance of sickle cell forms of erythrocytes.

The reason for the appearance of sickle-shaped red blood cells is that hemoglobin S in the deoxygenated state has 100 times less solubility than hemoglobin A, and high ability to polymerization. As a result, oblong crystals form inside the red blood cell, which give the red blood cell a sickle shape. Such red blood cells become rigid, lose their plastic properties and are easily hemolyzed.

In the case of homozygous carriage we speak of sickle cell anemia, and in case of heterozygous carriage - about sickle cell anomaly. The disease is common in the countries of the “malarial belt” of the globe (countries of the Mediterranean, the Near and Middle East, North and West Africa, India, Georgia, Azerbaijan, etc.). The presence of hemoglobin S in heterozygous carriers provides them with protection from tropical malaria. In residents of these countries, hemoglobin S occurs in up to 40% of the population.

The homozygous form of the disease is characterized by moderate normochromic anemia, the total hemoglobin content is 60-80 g/l. The number of reticulocytes is increased - 10% or more. The average lifespan of red blood cells is about 17 days. A characteristic feature is the presence in the stained smear of sickle-shaped erythrocytes, erythrocytes with basophilic puncture.

Hemolysis of red blood cells contributes to the development of thrombotic complications. Multiple thromboses of the vessels of the spleen, lungs, joints, liver, and meninges may occur, followed by the development of infarction in these tissues. Depending on the localization of thrombosis in sickle cell anemia, several syndromes are distinguished - thoracic, musculoskeletal, abdominal, cerebral, etc. The worsening of anemia may be associated with a hypoplastic crisis, which is most often found in children against the background past infection. In this case, inhibition of bone marrow hematopoiesis is noted and reticulocytes disappear in the peripheral blood, the number of red blood cells, neutrophils and platelets decreases.

A hemolytic crisis can be provoked in patients with sickle cell anemia by infectious diseases, stress, and hypoxia. During these periods, the number of red blood cells sharply decreases, the level of hemoglobin drops, black urine appears, icteric discoloration of the skin and mucous membranes appears, and indirect bilirubin in the blood increases.

In addition to aplastic and hemolytic crises in sickle cell anemia, sequestration crises are observed, in which a significant part of the red blood cells is deposited in internal organs, in particular in the spleen. When red blood cells are deposited in internal organs, they may be destroyed at the deposit sites, although in some cases red blood cells are not destroyed during deposit.

The heterozygous form of hemoglobinopathy S (sickle cell anomaly) is asymptomatic in most patients, since the content pathological hemoglobin in erythrocytes is small. A small percentage of heterozygous carriers of abnormal hemoglobin during hypoxic conditions (pneumonia, rise to altitude) may have dark urine and various thrombotic complications.

Thalassemia. This is a group of diseases with a hereditary disorder of the synthesis of one of the globin chains, hemolysis, hypochromia and ineffective erythrocytopoiesis.

Thalassemia is common in the countries of the Mediterranean, Central Asia, Transcaucasia, etc. Environmental and ethnic factors, consanguineous marriages, and the incidence of malaria in a given area play a significant role in its spread.

The disease was first described by American pediatricians Cooley and Lee in 1925 (probably a homozygous form of α-thalassemia).

The etiological factor in thalassemia is mutations of regulatory genes, the synthesis of abnormally unstable or non-functioning messenger RNA, which leads to disruption of the formation of the α-, β-, γ-, and δ-chain of hemoglobin. It is possible that the development of thalassemia is based on hard mutations of structural genes such as deletions, which can also be accompanied by a decrease in the synthesis of the corresponding globin polypeptide chains. Depending on the disturbance in the synthesis of certain polypeptide chains of hemoglobin, α-, β-, δ- and βδ-thalassemia is distinguished, however, each form is based on a deficiency of the main fraction of hemoglobin - HbA.

Normally, the synthesis of various polypeptide chains of hemoglobin is balanced. In pathology, in the case of a deficiency in the synthesis of one of the globin chains, excess production of other polypeptide chains occurs, which leads to the formation excessive concentrations unstable abnormal hemoglobins of various types. The latter have the ability to precipitate and fall out in the erythrocyte in the form of “inclusion bodies”, giving them the shape of targets.

Classification of thalassemias:

1. Thalassemia caused by impaired synthesis of the α-globin chain (α-thalassemia and diseases caused by the synthesis of hemoglobins H and Brats).

2. Thalassemia caused by impaired synthesis of β- and δ-chains of globin (β-thalassemia and β-, δ-thalassemia).

3. Hereditary persistence of fetal hemoglobin, i.e. a genetically determined increase in hemoglobin F in adults.

4. Mixed group - double heterozygous states for the thalassemia gene and the gene for one of the “qualitative” hemoglobinapathies.

α-thalassemia. The gene responsible for the synthesis of the α chain is encoded by two pairs of genes located on the 11th chromosome. One of the pairs is manifest, the other is secondary. In the case of development of α-thalassemia, gene deletion occurs. With homozygous dysfunction of all 4 genes, the globin α-chain is completely absent. Hemoglobin Brats is synthesized, which consists of four γ-chains that are unable to carry oxygen.

Carriers of homozygous α-thalassemia are not viable - the fetus dies in utero due to dropsy.

One of the forms of α-thalassemia is hemoglobinopathy H. With this pathology, there is a deletion of three genes encoding the synthesis of hemoglobin α-chains. Due to a deficiency of α-chains, abnormal hemoglobin H is synthesized, consisting of 4 β-chains. The disease is characterized by a decrease in the number of erythrocytes, hemoglobin (70-80 g/l), severe hypochromia of erythrocytes, their target appearance and basophilic punctation. The number of reticulocytes is moderately increased.

Deletion in one or two genes encoding the α chain causes a slight deficiency of hemoglobin A and is manifested by mild hypochromic anemia, the presence of red blood cells with basophilic punctuation and target red blood cells, and slight increase reticulocyte level. As with other forms of hemolytic anemia, with heterozygous α-thalassemia, icteric discoloration of the skin and mucous membranes and an increase in indirect bilirubin in the blood are noted.

β-thalassemia. It is more common than α-thalassemia and can be found in homozygous and heterozygous forms. The gene encoding the synthesis of the β chain is located on chromosome 16. Nearby are the genes responsible for the synthesis of globin γ- and δ-chains. In the pathogenesis of β-thalassemia, in addition to gene deletion, there is a violation of splicing, leading to a decrease in mRNA stability.

Homozygous β-thalassemia (Cooley's disease). The disease is most often detected in children aged 2 to 8 years. Jaundice discoloration of the skin and mucous membranes, enlarged spleen, deformations of the skull and skeleton, and stunted growth appear. In severe forms of homozygous β-thalassemia, these symptoms appear already in the first year of a child’s life. The prognosis is unfavorable.

From the blood side, signs of severe hypochromic anemia are detected (CP about 0.5), a decrease in hemoglobin to 20-50 g/l, the number of red blood cells in the peripheral blood is 1-2 million per day.

Heterozygous β-thalassemia. Characterized by a more benign course, signs of the disease appear in more advanced late age and are less pronounced. Anemia is moderate. The content of red blood cells is about 3 million in 1 micron, hemoglobin is 70-100 g/l. The content of reticulocins is 2-5% in peripheral blood. Aniso- and poikilocytosis, target-like erythrocytes are often detected; basophilic punctured erythrocytes are typical. The iron content in serum is usually normal, less often - slightly increased. In some patients, indirect serum bilirubin may be slightly increased.

Unlike the homozygous form, with heterozygous β-thalassemia there are no skeletal deformities and no growth retardation.

The diagnosis of β-thalassemia (homo- and heterozygous forms) is confirmed by an increase in the content of fetal hemoglobin (HbF) and HbA2 in erythrocytes.

Bibliographic link

Chesnokova N.P., Morrison V.V., Nevvazhay T.A. LECTURE 5. HEMOLYTIC ANEMIA, CLASSIFICATION. DEVELOPMENT MECHANISMS AND HEMATOLOGICAL CHARACTERISTICS OF CONGENITAL AND HERITAGE HEMOLYTIC ANEMIA // International Journal of Applied and Fundamental Research. – 2015. – No. 6-1. – pp. 162-167;
URL: https://applied-research.ru/ru/article/view?id=6867 (access date: 03/20/2019). We bring to your attention magazines published by the publishing house "Academy of Natural Sciences"

Anemia, in which the process of destruction of red blood cells prevails over the process of regeneration, is called hemolytic.

Classification of hemolytic anemias

Hemolytic anemia They have a number of characteristics that distinguish them from anemias of other origins. First of all, these are hyperregenerative anemias, occurring with hemolytic jaundice and splenomegaly. High reticulocytosis in hemolytic anemia is due to the fact that during the breakdown of red blood cells, all the necessary elements are formed for the construction of a new red blood cell and, as a rule, there is no deficiency of erythropoietin, vitamin B 12, folic acid and iron. The destruction of red blood cells is accompanied by an increase in the content of free bilirubin in the blood; when its level exceeds 25 µmol/l, hysteria of the sclera and skin appears. Enlargement of the spleen (splenomegaly) is the result of hyperplasia of its reticulohistiocytic tissue, caused by increased hemolysis of red blood cells. There is no generally accepted classification of hemolytic anemia.

Hereditary hemolytic anemia.

A. Membranopathies due to disruption of the structure of the erythrocyte membrane protein:

Microspherocytosis; elliptocytosis; stomatocytosis; piropoikilocytosis
Disorders of erythrocyte membrane lipids: acanthocytosis, deficiency of lecithin-cholesterol acyltransferase activity, increased lecithin content in the erythrocyte membrane, infantile pycnocytosis

B. Enzymepathies:

Pentose phosphate cycle enzyme deficiency
Deficiency of glycolytic enzyme activity
Deficiency of glutathione metabolic enzyme activity
Deficiency in the activity of enzymes involved in the use of ATP
Ribophosphate pyrophosphate kinase activity deficiency
Impaired activity of enzymes involved in the synthesis of porphyrins

B. Hemoglobinopathies:

Caused by an anomaly in the primary structure of hemoglobin
Caused by a decrease in the synthesis of polypeptide chains that make up normal hemoglobin
Caused by a double heterozygous state
Hemoglobin abnormalities not accompanied by the development of the disease

Acquired hemolytic anemia

A. Immune hemolytic anemias:

Hemolytic anemias associated with exposure to antibodies: isoimmune, heteroimmune, transimmune
Autoimmune hemolytic anemia: with incomplete warm agglutinins, with warm hemolysins, with complete cold agglutinins, associated with biphasic cold hemolysins
Autoimmune hemolytic anemia with antibodies against bone marrow normocyte antigen

B. Hemolytic anemia associated with membrane changes caused by somatic mutation: PNH

B. Hemolytic anemia associated with mechanical damage to the erythrocyte membrane

D. Hemolytic anemia associated with chemical damage to red blood cells (lead, acids, poisons, alcohol)

D. Hemolytic anemia due to deficiency of vitamins E and A

At the stage of a clinical blood test, a laboratory doctor examines the morphology of red blood cells. In this case, various changes can be detected: micro-, sphero-, oval-, ellipto-, stomato-, acantho-, pyropycnocytosis, target-like erythrocytes, which gives reason to assume one of the variants of membranopathy, and the target-shaped erythrocytes are characteristic of thalassemia. If there are Heinz-Ehrlich bodies in erythrocytes against the background of anisopoikilocytosis, one of the variants of hereditary fermentopathy can be assumed. For sickle cell hemolytic anemia, a metabisulfite test or a test with a sealed drop of blood is performed, which increases the number of sickle red blood cells and thereby facilitates diagnosis. Intravascular hemolysis is manifested by the presence of fragmented red blood cells, the number of which sometimes reaches 100%, which is observed in disseminated intravascular coagulation syndrome, which accompanies many serious diseases, as well as in case of poisoning with hemolytic poisons, marching hemolysis and with an artificial heart valve. Thus, the altered morphology of erythrocytes, characteristic of certain variants of hemolytic anemia, allows us to justify further diagnostic search.

Already at the first acquaintance with a patient with anemia, it is advisable to find out his belonging to one or another ethnic group, since it is known that Azerbaijanis, residents of Dagestan, Georgians and Mountain Jews are more likely to suffer from hereditary hemolytic anemia. You should ask the patient if there are any patients with anemia among his blood relatives, when the first symptoms of anemia appeared, when anemia was first diagnosed. The hereditary nature of hemolytic anemia is sometimes indicated by the presence of cholelithiasis diagnosed in the patient or his relatives in at a young age(hyperbilirubinemia can promote stone formation in the gallbladder and ducts).

At physical examination In patients with hereditary hemolytic anemia, in some cases changes in the bone skeleton and skull structure are detected. The combination of anamnesis data, results of physical and laboratory tests allows us to determine the hemolytic nature of anemia. Further research is aimed at clarifying the main pathogenetic link of hemolytic anemia.

There are clinical and laboratory differences between intravascular and intracellular hemolysis. Thus, when red blood cells are destroyed in the spleen, liver, and bone marrow, heme catabolism occurs in macrophages: under the influence of the enzyme heme oxygenase, verdohemoglobin is formed, iron is cleaved off, then biliverdin is formed, which, under the influence of biliverdin reductase, is converted into bilirubin. Once in the general bloodstream, bilirubin binds to albumin; in the liver, albumin is cleaved off, and bilirubin combines with glucuronic acid, forming bilirubin mono- and diglucuronide, which enter the bile and are released into the intestines. There, under the influence of microflora, it turns into urobilinogen, and then into stercobilin. This process is similar to the physiological one: approximately 1% of red blood cells die daily, mainly in the reticulohistiocytic system of the spleen, liver, and bone marrow. But with hemolytic anemia, hemolysis increases sharply, therefore, the content of free bilirubin in the blood increases, its excretion into bile increases, disrupting its colloidal stability, and preconditions are created for the development of cholelithiasis.

– pathology of erythrocytes, hallmark which is the accelerated destruction of red blood cells with the release increased amount indirect bilirubin. For this group of diseases, a typical combination of anemic syndrome, jaundice and an increase in the size of the spleen is typical. During the diagnostic process, a general blood test, bilirubin level, stool and urine analysis, and ultrasound of the abdominal organs are examined; A bone marrow biopsy and immunological studies are performed. Treatment methods include medications and blood transfusion therapy; In case of hypersplenism, splenectomy is indicated.

ICD-10

D59 D58

General information

Hemolytic anemia (HA) is anemia caused by a disorder life cycle erythrocytes, namely the predominance of the processes of their destruction (erythrocytolysis) over formation and maturation (erythropoiesis). This group Anemia is very widespread. Their prevalence varies across different latitudes and age cohorts; On average, the pathology occurs in 1% of the population. Among other types of anemia, hemolytic ones account for 11%. The pathology is characterized by a shortening of the life cycle of red blood cells and their breakdown (hemolysis) ahead of time (after 14-21 days instead of 100-120 days normally). In this case, the destruction of red blood cells can occur directly in the vascular bed (intravascular hemolysis) or in the spleen, liver, bone marrow (extravascular hemolysis).

Causes

The etiopathogenetic basis of hereditary hemolytic syndromes is genetic defects membranes of erythrocytes, their enzyme systems or the structure of hemoglobin. These prerequisites determine the morphofunctional inferiority of erythrocytes and their increased destruction. Hemolysis of red blood cells in acquired anemia occurs under the influence of internal or environmental factors, including:

Autoimmune processes. The formation of antibodies that agglutinate red blood cells is possible in hemoblastoses (acute leukemia, chronic lymphocytic leukemia, lymphogranulomatosis), autoimmune pathology (SLE, nonspecific ulcerative colitis), infectious diseases (infectious mononucleosis, toxoplasmosis, syphilis, viral pneumonia). The development of immune hemolytic anemia can be facilitated by post-transfusion reactions, preventive vaccination, and hemolytic disease of the fetus.
Toxic effect on red blood cells. In some cases, acute intravascular hemolysis is preceded by poisoning with arsenic compounds, heavy metals, acetic acid, mushroom poisons, alcohol, etc. Taking certain medications (antimalarials, sulfonamides, nitrofuran derivatives, analgesics) can cause destruction of blood cells.
Mechanical damage to red blood cells. Hemolysis of red blood cells may occur in severe physical activity(long walking, running, skiing), with disseminated intravascular coagulation syndrome, malaria, malignant arterial hypertension, prosthetic heart valves and blood vessels, hyperbaric oxygen therapy, sepsis, extensive burns. In these cases, under the influence of certain factors, traumatization and rupture of the membranes of initially full-fledged red blood cells occurs.

Pathogenesis

The central link in the pathogenesis of HA is the increased destruction of red blood cells in the organs of the reticuloendothelial system (spleen, liver, bone marrow, lymph nodes) or directly in the vascular bed. With the autoimmune mechanism of anemia, the formation of anti-erythrocyte antibodies (heat, cold) occurs, which cause enzymatic lysis of the erythrocyte membrane. Toxic substances, being strong oxidizing agents, destroy red blood cells due to the development of metabolic, functional and morphological changes in the membrane and stroma of red blood cells. Mechanical factors have a direct impact on cell membrane. Under the influence of these mechanisms, potassium and phosphorus ions leave the erythrocytes, and sodium ions enter inside. The cell swells when critical increase its volume, hemolysis occurs. The breakdown of red blood cells is accompanied by the development of anemic and icteric syndromes (the so-called “pale jaundice”). Possible intense staining of feces and urine, enlargement of the spleen and liver.

Classification

In hematology, hemolytic anemias are divided into two large groups: congenital (hereditary) and acquired. Hereditary GAs include the following forms:

erythrocyte membranopathies(microspherocytosis - Minkowski-Choffard disease, ovalocytosis, acanthocytosis) - anemia caused by structural abnormalities of erythrocyte membranes
fermentopenia(enzymopenia) – anemia caused by a deficiency of certain enzymes (glucose-6-phosphate dehydrogenase, pyruvate kinase, etc.)
hemoglobinopathies- anemia associated with qualitative disturbances in the structure of hemoglobin or changes in the ratio of its normal forms (thalassemia, sickle cell anemia).

Acquired GAs are divided into:

acquired membranopathy(paroxysmal nocturnal hemoglobinuria - Marchiafava-Micheli disease, spur cell anemia)
immune (auto- and isoimmune)– caused by the influence of antibodies
toxic– anemia caused by exposure chemical substances, biological poisons, bacterial toxins
mechanical- anemia caused by mechanical damage to the structure of erythrocytes (thrombocytopenic purpura, march hemoglobinuria)

Symptoms

Hereditary membranopathies, enzymopenias and hemoglobinopathies

The most common form of this group of anemias is microspherocytosis, or Minkowski-Choffard disease. Inherited in an autosomal dominant manner; usually traced to several members of the family. The defectiveness of erythrocytes is caused by a deficiency of actomyosin-like protein and lipids in the membrane, which leads to a change in the shape and diameter of erythrocytes, their massive and premature hemolysis in the spleen. Manifestation of microspherocytic HA is possible at any age (in infancy, adolescence, old age), but usually manifestations occur in older children and adolescents. The severity of the disease varies from sub clinical course to severe forms, characterized by frequently recurring hemolytic crises. At the moment of crisis, body temperature, dizziness, and weakness increase; Abdominal pain and vomiting occur.

The main symptom of microspherocytic hemolytic anemia is jaundice of varying degrees of intensity. Due to high content stercobilin stool becomes intensely colored dark brown color. Patients with Minkowski-Choffard disease have a tendency to form stones in the gall bladder, therefore, signs of exacerbation of calculous cholecystitis often develop, attacks of biliary colic occur, and when the common bile duct is blocked by a stone, obstructive jaundice occurs. With microspherocytosis, in all cases the spleen is enlarged, and in half of the patients the liver is also enlarged. In addition to hereditary microspherocytic anemia, children often experience other congenital dysplasia: tower skull, strabismus, saddle nose deformation, malocclusion, gothic palate, polydactyly or bradydactyly, etc. Middle-aged and elderly patients suffer from trophic ulcers of the leg, which arise as a result of hemolysis of red blood cells in the capillaries of the extremities and are difficult to treat.

Enzymopenic anemia is associated with a deficiency of certain red blood cell enzymes (usually G-6-PD, glutathione-dependent enzymes, pyruvate kinase, etc.). Hemolytic anemia may first manifest itself after suffering an intercurrent illness or taking medications (salicylates, sulfonamides, nitrofurans). Usually the disease has a smooth course; “pale jaundice”, moderate hepatosplenomegaly, and heart murmurs are typical. In severe cases, a pronounced picture of a hemolytic crisis develops (weakness, vomiting, shortness of breath, palpitations, collapsing state). Due to intravascular hemolysis of erythrocytes and the release of hemosiderin in the urine, the latter acquires a dark (sometimes black) color. Independent reviews are devoted to the features of the clinical course of hemoglobinopathies - thalassemia and sickle cell anemia.

Acquired hemolytic anemia

Among the various acquired variants, autoimmune anemia is the most common. For them, a common trigger is the formation of antibodies to antigens of their own red blood cells. Hemolysis of erythrocytes can be both intravascular and intracellular in nature. Hemolytic crisis in autoimmune anemia develops acutely and suddenly. It occurs with fever, severe weakness, dizziness, palpitations, shortness of breath, pain in the epigastrium and lower back. Sometimes acute manifestations are preceded by precursors in the form of low-grade fever and arthralgia. During a crisis, jaundice rapidly increases, not accompanied by itching, and the liver and spleen enlarge. In some forms of autoimmune anemia, patients do not tolerate cold well; in low temperatures they may develop Raynaud's syndrome, urticaria, and hemoglobinuria. Due to circulatory failure in small vessels, complications such as gangrene of the toes and hands are possible.

Toxic anemia occurs with progressive weakness, pain in the right hypochondrium and lumbar region, vomiting, hemoglobinuria, high body temperature. From 2-3 days jaundice and bilirubinemia develop; on days 3-5, liver and kidney failure occurs, signs of which are hepatomegaly, fermentemia, azotemia, and anuria. Certain types of acquired hemolytic anemia are discussed in the relevant articles: “Hemoglobinuria” and “Thrombocytopenic purpura”, “Hemolytic disease of the fetus”.

Complications

Each type of GA has its own specific complications: for example, cholelithiasis - with microspherocytosis, liver failure– for toxic forms, etc. To the number general complications include hemolytic crises, which can be provoked by infections, stress, and childbirth in women. In acute massive hemolysis, the development of hemolytic coma is possible, characterized by collapse, confusion, oliguria, and increased jaundice. The patient's life is threatened by disseminated intravascular coagulation syndrome, splenic infarction, or spontaneous organ rupture. Acute cardiovascular and renal failure require emergency medical care.

Diagnostics

Determining the form of HA based on an analysis of causes, symptoms and objective data falls within the competence of a hematologist. During the initial conversation, family history, frequency and severity of hemolytic crises are clarified. During the examination, the color of the skin, sclera and visible mucous membranes is assessed, and the abdomen is palpated to assess the size of the liver and spleen. Spleno- and hepatomegaly are confirmed by ultrasound of the liver and spleen. Laboratory diagnostic complex includes:

Blood test. Changes in the hemogram are characterized by normo- or hypochromic anemia, leukopenia, thrombocytopenia, reticulocytosis, and accelerated ESR. Biochemical blood samples reveal hyperbilirubinemia (increased indirect bilirubin fraction) and increased lactate dehydrogenase activity. In autoimmune anemia, a large diagnostic value has a positive Coombs test.
Urine and stool tests. Urine examination reveals proteinuria, urobilinuria, hemosiderinuria, hemoglobinuria. The coprogram has an increased content of stercobilin.
Myelogram. For cytological confirmation, a sternal puncture is performed. Examination of bone marrow puncture reveals hyperplasia of the erythroid lineage.

In the process of differential diagnosis, hepatitis, liver cirrhosis, portal hypertension, hepatolienal syndrome, porphyria, and hemoblastosis are excluded. The patient is consulted by a gastroenterologist, clinical pharmacologist, infectious disease specialist and other specialists.

Treatment

Different forms of GA have their own characteristics and approaches to treatment. For all types of acquired hemolytic anemia, care must be taken to eliminate the influence of hemolyzing factors. During hemolytic crises, patients need infusions of solutions and blood plasma; vitamin therapy, and, if necessary, hormone and antibiotic therapy. For microspherocytosis, the only effective method leading to 100% cessation of hemolysis is splenectomy.

For autoimmune anemia, therapy with glucocorticoid hormones (prednisolone), which reduces or stops hemolysis, is indicated. In some cases, the required effect is achieved by prescribing immunosuppressants (azathioprine, 6-mercaptopurine, chlorambucil), antimalarial drugs (chloroquine). For forms of autoimmune anemia resistant to drug therapy, splenectomy is performed. Treatment of hemoglobinuria involves transfusion of washed red blood cells, plasma substitutes, and the prescription of anticoagulants and antiplatelet agents. The development of toxic hemolytic anemia dictates the need for intensive care: detoxification, forced diuresis, hemodialysis, according to indications - administration of antidotes.

Prognosis and prevention

The course and outcome depend on the type of anemia, the severity of the crises, completeness pathogenetic therapy. With many acquired variants, elimination of the causes and full treatment leads to complete recovery. A cure for congenital anemia cannot be achieved, but long-term remission can be achieved. With the development of renal failure and other fatal complications, the prognosis is unfavorable. The development of HA can be prevented by the prevention of acute infectious diseases, intoxication, poisoning. Uncontrolled independent use medications. It is necessary to carefully prepare patients for blood transfusions and vaccinations with the full range of necessary examinations.