Hemolytic anemia. Other forms of hemolytic anemia

Immune hemolysis in adults is usually caused by IgG and IgM autoantibodies to self-red blood cell antigens. With the acute onset of autoimmune hemolytic anemia, patients develop weakness, shortness of breath, palpitations, pain in the heart and lower back, the temperature rises, and intense jaundice develops. In the chronic course of the disease, general weakness, jaundice, enlargement of the spleen, and sometimes the liver are detected.

Anemia is normochromic. Macrocytosis and microspherocytosis are detected in the blood, and normoblasts may appear. ESR is increased.

The main method for diagnosing autoimmune hemolytic anemia is the Coombs test, in which antibodies to immunoglobulins (especially IgG) or complement components (C3) agglutinate the patient’s red blood cells (direct Coombs test).

In some cases, it is necessary to detect antibodies in the patient's serum. To do this, the patient's serum is first incubated with normal red blood cells, and then antibodies against them are detected using antiglobulin serum (anti-IgG) - an indirect Coombs test.

IN rare cases Neither IgG nor complement is detected on the surface of red blood cells (immune hemolytic anemia with a negative Coombs test).

Autoimmune hemolytic anemia with warm antibodies

Autoimmune hemolytic anemia with warm antibodies most often develops in adults, especially women. Warm antibodies refer to IgG that react with protein antigens of red blood cells at body temperature. This anemia can be idiopathic and drug-induced and is observed as a complication of hemoblastosis ( chronic lymphocytic leukemia, lymphogranulomatosis, lymphoma), collagenosis, especially SLE, AIDS.

The clinical picture of the disease is manifested by weakness, jaundice, and splenomegaly. With severe hemolysis, patients develop fever, fainting, pain in the chest and hemoglobinuria.

Laboratory findings are characteristic of extravascular hemolysis. Anemia is detected with a decrease in hemoglobin level to 60-90 g/l, the content of reticulocytes increases to 15-30%. The direct Coombs test is positive in more than 98% of cases; IgG is detected in combination with or without SZ. Hemoglobin levels are reduced. In a smear peripheral blood microspherocytosis is found.

Mild hemolysis does not require treatment. For moderate to severe hemolytic anemia, treatment is primarily aimed at the cause of the disease. To quickly stop hemolysis, use normal immunoglobulin G 0.5-1.0 g/kg/day intravenously for 5 days.

Against hemolysis itself, glucocorticoids are prescribed (for example, prednisolone 1 mg/kg/day orally) until hemoglobin levels normalize within 1-2 weeks. After this, the dose of prednisolone is reduced to 20 mg/day, then continued to be reduced for several months and discontinued completely. A positive result is achieved in 80% of patients, but in half of them the disease recurs.

If glucocorticoids are ineffective or intolerant, splenectomy is indicated, which gives a positive result in 60% of patients.

In the absence of effect from glucocorticoids and splenectomy, immunosuppressants are prescribed - azathioprine (125 mg/day) or cyclophosphamide (100 mg/day) in combination with or without prednisolone. The effectiveness of this treatment is 40-50%.

In case of severe hemolysis and severe anemia, blood transfusion is performed. Since warm antibodies react with all red blood cells, the usual selection compatible blood not applicable. First, the antibodies present in the patient’s serum should be adsorbed using his own red blood cells, from the surface of which the antibodies have been removed. After this, the serum is tested for the presence of alloantibodies to antigens of donor red blood cells. Selected red blood cells are slowly transfused to patients under careful monitoring for the possible occurrence of a hemolytic reaction.

Autoimmune hemolytic anemia with cold antibodies

This anemia is characterized by the presence of autoantibodies that react at temperatures below 37 °C. There is an idiopathic form of the disease, accounting for about half of all cases, and an acquired form associated with infections (mycoplasma pneumonia and infectious mononucleosis) and lymphoproliferative conditions.

The main symptom of the disease is increased sensitivity to cold (general hypothermia or ingestion of cold food or drinks), manifested by blueness and whiteness of the fingers and toes, ears, and tip of the nose.

Characteristic disorders peripheral circulation(Raynaud's syndrome, thrombophlebitis, thrombosis, sometimes cold urticaria), resulting from intra- and extravascular hemolysis, leading to the formation of intravascular conglomerates of agglutinated erythrocytes and occlusion of microcirculatory vessels.

Anemia is usually normochromic or hyperchromic. In the blood, reticulocytosis is detected, normal amount leukocytes and platelets, high titer of cold agglutinins, usually IgM and S3 class antibodies. Direct Coombs test reveals only SZ. Agglutination of erythrocytes in vitro at room temperature is often detected, which disappears when heated.

Paroxysmal cold hemoglobinuria

The disease is currently rare and can be either idiopathic or caused by viral infections(measles or mumps in children) or tertiary syphilis. In pathogenesis, the formation of biphasic Donath-Landsteiner hemolysins is of primary importance.

Clinical manifestations develop after exposure to cold. During an attack, chills and fever, pain in the back, legs and abdomen occur, headache and general malaise, hemoglobinemia and hemoglobinuria.

The diagnosis is made after the detection of cold Ig antibodies in a two-phase hemolysis test. The direct Coombs test is either negative or reveals SZ on the surface of red blood cells.

The main thing in the treatment of autoimmune hemolytic anemia with cold autoantibodies is to prevent the possibility of hypothermia. In the chronic course of the disease, prednisolone and immunosuppressants (azathioprine, cyclophosphamide) are used. Splenectomy is usually ineffective.

Autoimmune drug-induced hemolytic anemia

Medicines that cause immune hemolytic anemia pathogenetic mechanism actions are divided into three groups.

The first group includes drugs causing disease, the clinical signs of which are similar to those of autoimmune hemolytic anemia with warm antibodies. In most patients, the cause of the disease is methyldopa. When taking this drug at a dose of 2 g/day, 20% of patients have a positive Coombs test. In 1% of patients, hemolytic anemia develops; microspherocytosis is detected in the blood. IgG is found on erythrocytes. Hemolysis subsides several weeks after discontinuation of methyldopa.

The second group includes drugs that are adsorbed on the surface of erythrocytes, act as haptens and stimulate the formation of antibodies to the drug-erythrocyte complex. Such drugs are penicillin and other antibiotics similar in structure. Hemolysis develops when the drug is prescribed in high doses (10 million units/day or more), but is usually moderate and quickly stops after discontinuation of the drug. The Coombs test for hemolysis is positive.

The third group includes drugs (quinidine, sulfonamides, sulfonylurea derivatives, phenycytin, etc.), causing formation specific antibodies of the IgM complex. The interaction of antibodies with drugs leads to the formation of immune complexes that settle on the surface of red blood cells.

The direct Coombs test is positive only in relation to SZ. Indirect sample Coombs' test is positive only in the presence of a drug. Hemolysis is often intravascular and resolves quickly after discontinuation. medicines.

Mechanical hemolytic anemia

Mechanical damage to red blood cells leading to the development of hemolytic anemia occurs:

• as red blood cells pass through small vessels above the bony prominences, where they are subjected to pressure from the outside ( March hemoglobinuria);
• when overcoming the pressure gradient on the prostheses of the valves of the heart and blood vessels;
• when passing through small vessels with altered walls (microangiopathic hemolytic anemia).

March hemoglobinuria occurs after prolonged walking or running, karate or weightlifting and is manifested by hemoglobinemia and hemoglobinuria.

Hemolytic anemia in patients with prosthetic heart valves and blood vessels is caused by intravascular destruction of red blood cells. Hemolysis develops in approximately 10% of patients with prosthetic aortic valve(stellite valves) or its dysfunction (perivalvular regurgitation). Bioprostheses (pig valves) and artificial mitral valves rarely cause significant hemolysis. Mechanical hemolysis is found in patients with aortofemoral bypass grafts.

Hemoglobin decreases to 60-70 g/l, reticulocytosis and schizocytes (red blood cell fragments) appear, hemoglobin content decreases, hemoglobinemia and hemoglobinuria occur.

Treatment is aimed at reducing oral iron deficiency and limiting physical activity, which reduces the intensity of hemolysis.

Microangiopathic hemolytic anemia

It is a variant of mechanical intravascular hemolysis. The disease occurs with thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, disseminated intravascular coagulation syndrome, pathology vascular wall (hypertensive crises, vasculitis, eclampsia, disseminated malignant tumors).

In the pathogenesis of this anemia, the deposition of fibrin threads on the walls of arterioles, through the interlacing of which red blood cells are destroyed, is of primary importance. Fragmented red blood cells (schizocytes and helmet cells) and thrombocytopenia are detected in the blood. Anemia is usually severe, the hemoglobin level decreases to 40-60 g/l.

The underlying disease is treated, glucocorticoids, fresh frozen plasma, plasmapheresis and hemodialysis are prescribed.

Anemia is a disease characterized by a decrease in the level of hemoglobin and red blood cells in the blood. They have, depending on their origin, several forms. Thus, iron deficiency anemia develops due to iron deficiency.

This form is the most common. After suffering from a serious illness, an infectious disease occurs. And as a result of accelerated destruction of red blood cells, hemolytic anemia develops.

Causespathological process

They are mainly congenital defects of glycolytic enzymes, as well as disturbances in the composition of hemoglobin. They are what make red blood cells less resistant and prone to accelerated destruction. Infections, medications, and poisoning can also be the direct cause of hemolysis. In some cases, an autoimmune process occurs in which antibodies are formed that stick together red blood cells.

Forms of hemolytic anemia

They can be congenital or acquired. Both of them have several varieties.

Congenital hemolytic anemia is inherited. Its symptoms depend on the subspecies. But a common symptom for all hemoglobinoses is icteric staining of visible mucous membranes and skin. For this reason, they are often confused with liver diseases. So, the most common among congenital hemolytic anemias are:

1. Thallasemia. With this disease, embryonic fetal hemoglobin F predominates in red blood cells. It is characterized by progressive anemia, enlargement of the spleen and liver. The bones of the skull (occipital and parietal tubercles) grow disproportionately, as the erythroblastic lineage increases in the bone marrow.

2. Hemoglobinosis C. Manifested by hyperplasia bone marrow, bilirubinemia, moderate jaundice. Pain crises (rheumatoid) are observed.

This type of hemolytic anemia is considered a relatively mild form. It proceeds benignly and does not give serious consequences and complications.

3. Erythrocytopathies. The main symptoms - jaundice, splenomegaly and anemia - are observed in childhood. This form of the disease is severe, accompanied by often recurring hemolytic crises. They arise under the influence of many provoking factors (infections, hypothermia, etc.). Hemolytic crises occur with fever and severe chills. In many patients, enlargement of the liver and spleen is complemented by the development of calculous cholecystitis. Often the skeleton of such patients has the following anomalies: saddle nose, tower skull, high rise of the hard palate. Hemolytic anemia can not only be inherited, but also acquired during life.

Forms of acquired anemia

1. Acquired acute hemolytic anemia. The disease starts with sharp jump temperature up to 40°, weakness, yellowness of the skin and visible to the eye mucous membranes. Sometimes dyspeptic symptoms appear. There are significant disturbances in the functioning of the heart: tachycardia, hypotension, systolic murmur. In some cases this is possible serious condition, life-threatening, like collapse. The liver and spleen are enlarged. Urine becomes dark, almost black, due to the presence of protein and free hemoglobin in it. Rarely, the renal vessels are blocked by pigments and fragments of red blood cells, which leads to severe necrotic changes.

2. Acquired chronic hemolytic anemia. The disease progresses in waves. Periods of clinical improvement are followed by hemolytic crises. They manifest themselves as pain in the abdomen, lower back, and liver area. The mucous membranes and skin are pale and icteric. The temperature often rises. The liver and spleen, as a rule, do not enlarge. At severe course hemolytic crises may cause blockage of the renal canals with subsequent necrosis.

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 there are hereditary and acquired hemolytic anemia, since they have different development mechanisms 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; pyropoykylocytosis

Violation of erythrocyte membrane lipids: acanthocytosis, deficiency of lecithin-cholesterol acyltransferase activity, an increase in the content of lecithin in the erythrocyte membrane, infantile infantile pycnocytosis

B. Fermentopathies:

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 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 clinical blood analysis, 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 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 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 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.

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 locations (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, the analysis of clinical and laboratory data helps to distinguish between intracellular and intravascular hemolysis, to approach the definition of a variant of hemolytic anemia. So, 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 characteristic of the population of Ukraine.

Microspherocytic hemolytic anemia.

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

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 the form of a mesh, through the holes of which many active substances necessary to ensure the stability of the membrane freely enter and exit. In this case, electrolyte metabolism is disturbed, since sodium and water penetrate into the erythrocyte in an increased amount, as a result of which the erythrocyte swells, becomes large, acquires a spherical shape. Subsequently, the size of the erythrocyte decreases during passage (passage) through the sinusoids of the spleen, its membrane is “cut” from the surface, and the erythrocyte decreases in size (microcytosis), while maintaining 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. Skin and visible mucous membranes varying degrees icteric, 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 healthy person decreases to 0.03-0.4%, and in patients with microspherocytic hemolytic anemia - up 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 the 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 residents of the Mediterranean coast, among Sephardic Jews, as well as in Africa and Latin America and in the former malarial areas of 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 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 jaundice 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 various typesß-thalassemias, as well as several types of a-thalassemias (i.e. quantitative hemoglobinopathies). 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.

These include congenital forms of the disease associated with the appearance of spherocytes, which undergo rapid destruction (the osmotic stability of red blood cells is reduced). This same group includes enzymopathic hemolytic anemias.

Anemia can be autoimmune, associated with the appearance of antibodies to blood cells.

All hemolytic anemias are characterized by increased destruction of erythrocytes, as a result of which the level of necrosis in the peripheral blood increases. direct bilirubin.

In autoimmune hemolytic anemia, an enlarged spleen may be detected; a laboratory test reveals a positive Coombs test.

B 12 - folate deficiency anemia is associated with a lack of vitamin B 12 and folic acid. This type of disease develops due to a lack of internal factor Castle or due to helminthic infestation. IN clinical picture Severe macrocytic anemia predominates. The color index is always increased. The size of the red blood cells is normal or increased in diameter. Symptoms of funicular myelosis are often observed (damage to the lateral trunks spinal cord), which manifests itself as parasthesia of the lower extremities. Sometimes this symptom is detected before anemia develops. Bone marrow puncture reveals the megalocytic type of hematopoiesis.

Aplastic anemia is characterized by inhibition (aplasia) of all hematopoietic lineages - erythroid, myeloma and platelet. Therefore, such patients are prone to infections and hemorrhages. In bone marrow aspirate, a decrease in cellularity and a decrease in all hematopoietic sprouts are observed.

Epidemiology. In the Mediterranean basin and equatorial Africa, hereditary hemolytic anemia ranks second, accounting for 20-40% of anemia.

Causes of hemolytic anemia

Hemolytic jaundice, or hemolytic anemia, was isolated from other types of jaundice by Minkowski and Shoffar in 1900. The disease is characterized by prolonged, periodically worsening jaundice, associated not with liver damage, but with increased breakdown of less resistant red blood cells in the presence of increased blood-destructive function of the spleen. Often the disease is observed in several family members, in several generations: changes in red blood cells are also characteristic; the latter are reduced in diameter and have the shape of a ball (and not a disk, as is normal), which is why it is proposed to call the disease “microspherocytic anemia” (Rare cases of sickle cell and oval cell anemia have been described, when red blood cells are also less stable and some patients develop hemolytic jaundice.) . In these. characteristics of red blood cells tended to see congenital anomaly red blood cells However, in Lately the same microspherocytosis was obtained under the influence of long-term exposure to small doses of hemolytic poisons. From this we can conclude that in case of familial hemolytic jaundice, the case is about the long-term action of some kind of poison, which is formed, possibly as a result of persistently disturbed metabolism or entering the patient's body from outside. This allows you to put family hemolytic jaundice on a par with hemolytic anemia of a certain symptomatic origin. Due to changes in the shape of erythrocytes in familial hemolytic anemia, they are less stable, are phagocytosed to a greater extent by active elements of the mesenchyme, especially the spleen, and undergo complete decay. From the hemoglobin of decaying red blood cells, bilirubin is formed, which is contained in the blood of the splenic vein much more than in the splenic artery (as can be seen during the operation of removing the spleen). In the development of the disease, violation of higher nervous activity, as evidenced by the worsening of the disease or its first detection, often after emotional moments. Activities of one of the most active organs hemorrhage - the spleen, as well as the hematopoietic organs, is undoubtedly constantly subject to regulation by the nervous system.

Hemolysis is compensated hard work bone marrow, which produces a large number of young red blood cells (reticulocytes), which for many years prevents the development of severe anemia.

The condition for the normal lifespan of erythrocytes is deformability, the ability to withstand osmotic and mechanical stress, normal restoration potential, as well as adequate energy production. Violation of these properties shortens the life span of erythrocytes, in some cases up to several days (corpuscular hemolytic anemia). General characteristics of these anemias is an increase in the concentration of erythropoietin, which provides compensatory stimulation of erythropoiesis under the created conditions.

Corpuscular hemolytic anemia is usually caused by genetic defects.

One of the forms of diseases in which the membrane is damaged is hereditary spherocytosis(spherocytic anemia). It is caused by a functional abnormality (ankyrin defect) or deficiency of spectrin, which is an essential component of the erythrocyte cytoskeleton and to a large extent determines its stability. The volume of spherocytes is normal, but disruption of the cytoskeleton causes the red blood cells to take on a spherical shape instead of the normal, easily deformable biconcave shape. The osmotic resistance of such cells is reduced, i.e., under continued hypotonic conditions they are hemolyzed. Such red blood cells are prematurely destroyed in the spleen, so splenectomy is effective for this pathology.

Defect of glucose metabolism enzymes in erythrocytes:

1. with a defect in pyruvate kinase, the formation of ATP decreases, the activity of Na + /K + -ATPase decreases, the cells swell, which contributes to their early hemolysis;
2. When glucose-6-phosphate dehydrogenase is defective, the pentose phosphate cycle is disrupted so that oxidized glutathione (GSSG) produced by oxidative stress cannot be adequately regenerated to the reduced form (GSH). As a result, free SH groups of enzymes and membrane proteins, as well as phospholipids, are unprotected from oxidation, which leads to premature hemolysis. Consumption of fava beans (Viciafabamajor, which causes favism) or certain drugs (primaquine or sulfonamides) increases the severity of oxidative stress, thereby exacerbating the situation;
3. a defect in hexokinase results in a deficiency of both ATP and GSH.

Sickle cell anemia and thalassemias also have a hemolytic component.

In (acquired) paroxysmal nocturnal hemoglobinuria, some red blood cells (derived from stem cells with somatic mutations) have increased sensitivity to the action of the complement system. It is caused by a defect in the membrane portion of the anchor (glycosylphosphatidylinositol) protein that protects red blood cells from the action of the complement system (especially decay accelerating factor CD55 or membrane reactive lysis inhibitor). These disorders lead to activation of the complement system with subsequent possible perforation of the erythrocyte membrane.

Extracorpuscular hemolytic anemia can be caused by the following reasons:

• mechanical, such as damage to red blood cells when they hit artificial heart valves or vascular prostheses, especially with increased cardiac output;
• immune, for example, during transfusion of ABO-incompatible blood, or during an Rh conflict between mother and fetus;
• the influence of toxins, such as some snake venoms.

In most hemolytic anemias, red blood cells, as in normal conditions, are phagocytosed and digested in the bone marrow, spleen and liver (extravascular hemolysis), and the released iron is utilized. Small amounts of iron released into the vascular bed bind to haptoglobin. However, with massive acute intravascular hemolysis, the level of haptoglobin increases and is filtered by the kidneys as free hemoglobin. This leads not only to hemoglobinuria (dark urine appears), but also due to tubular occlusion to acute renal failure. In addition, chronic hemoglobinuria is accompanied by the development of iron deficiency anemia, an increase in cardiac output and a further increase in mechanical hemolysis, leading to a vicious circle. Finally, fragments of erythrocytes formed during intravascular hemolysis can cause the formation of blood clots and emboli with subsequent development of ischemia of the brain, myocardium, kidneys and other organs.

Symptoms and signs of hemolytic anemia

Patients complain of weakness, decreased performance, periodic attacks of fever with chills, pain in the spleen and liver, increased weakness and the appearance of obvious jaundice. For years, sometimes from the first years of life, they have mild yellowness of the skin and sclera, usually also an enlarged spleen and anemia.

On examination, the integument is slightly lemon-yellow; in contrast to hepatic jaundice, there are no scratching and itching; developmental anomalies can often be detected - tower skull, saddle nose, widely spaced eye sockets, high sky, sometimes six-fingered.

From the side of the internal organs, the most constant sign - increase spleen, usually moderate, rarely significant splenomegaly; the spleen is painful during crises, when due to muscular protection it can be difficult to feel and respiratory excursions of the chest on the left are limited. The liver is usually not enlarged, although long term disease, the passage of bile saturated with bilirubin causes loss of pigment stones, sharp pain in the liver area (pigmentary colic) and enlargement of the organ itself.

Laboratory data. Port-wine urine due to high content urobilin, does not contain bilirubin and bile acids. The stools are more colored than usual (hypercholic stools), the release of urobilin (stercobilin) ​​reaches 0.5-1.0 per day instead of the normal 0.1-0.3. Serum golden color; the content of hemolytic (indirect) bilirubin was increased to 1-2-3 mg% (instead of 0.4 mg% normally, according to the diazoreagent method), the cholesterol content was slightly reduced.

Characteristic hematological changes in erythrocytes come down primarily to the following triad:

1. decrease in the osmotic stability of erythrocytes;
2. persistent significant reticulocytosis;
3. reduction in erythrocyte diameter.

Decreased osmotic resistance of erythrocytes. While normal erythrocytes are stored not only in saline solution salts (0.9%), but also in slightly less concentrated solutions and begin to hemolyze only with a 0.5% solution; with hemolytic jaundice, hemolysis begins already in a 0.7-0.8% solution. Therefore, if, for example, to a precisely prepared 0.6% solution sodium chloride add a drop of blood from a healthy person, then after centrifugation all the red blood cells will be in the sediment, and the solution will remain colorless; with hemolytic jaundice, the red blood cells in a 0.6% solution are partially hemolyzed, and the liquid turns pink.

To accurately establish the boundaries of hemolysis, take a series of test tubes with solutions table salt, for example, 0.8-0.78-0.76-0.74%, etc. up to 0.26-0.24-0.22-0.2% and mark the first tube with the onset of hemolysis (“ minimal resistance") and that test tube in which all the red blood cells were hemolyzed, and if the solution is drained, only a whitish precipitate of leukocytes and shadows of red blood cells will remain ("maximum resistance"). The normal limits of hemolysis are approximately 0.5 and 0.3% sodium chloride, with hemolytic jaundice usually 0.8-0.6% (onset) and 0.4-0.3% (complete hemolysis).

Reticulocytes are normally no more than 0.5-1.0%, but with hemolytic jaundice - up to 5-10% or more, with fluctuations only within relatively small limits during repeated studies over a number of years. Reticulocytes are counted in a fresh, unfixed smear made on glass with a thin layer of brilliant cresyl blue paint and on short term placed in a humid chamber.

The average diameter of erythrocytes instead of normal 7.5 μ in hemolytic jaundice is reduced to 6-6.5 μ; erythrocytes in the dative preparation do not give, as normally, the phenomenon of coin columns, and do not show retractions when viewed in profile.

The amount of hemoglobin is reduced more often to 60-50%, erythrocytes - up to 4,000,000-3,000,000; the color index fluctuates around 1.0. However, the numbers of red blood, due to enhanced regeneration, despite the increased breakdown of blood, can be almost normal; the number of leukocytes is normal or slightly increased.

Course, complications and prognosis of hemolytic anemia

The onset of the disease is usually gradual during puberty, sometimes the disease is detected already from the first days of life. Often the disease is detected for the first time after an accidental infection, overexertion, injury or surgery, anxiety, which in the future often serves as an impetus for the worsening of the disease, for a hemolytic crisis. Once it occurs, the disease lasts a lifetime. Indeed, in favorable cases, long periods mild or latent course of the disease.

The crisis is accompanied sharp pain in the area of ​​the spleen, then the liver, fever, often with chills (from the breakdown of the blood), a sharp increase in jaundice, severe weakness that confines the patient to bed, a drop in hemoglobin to 30-20% or lower and, accordingly, low numbers of red blood cells.

In case of pigmentary colic with blockage of the common bile duct by a stone, mechanical jaundice may be associated with discolored feces, itchy skin, the presence in the blood, in addition to hemolytic, also of hepatic (direct) bilirubin, icteric urine containing bilirubin, etc., which does not exclude hemolytic jaundice as the main disease. Severe damage to the liver parenchyma, in particular liver cirrhosis, does not develop even with a long-term course of the disease, just as depletion of bone marrow hematopoiesis does not occur.

The spleen may develop infarctions, perisplenitis, for a long time constituting the main complaint of patients or combined with severe anemia and general weakness sick.
Sometimes trophic ulcers develop on the legs, stubbornly resistant to local treatment and pathogenetically associated with increased hemolysis, for these ulcers quickly heal after the removal of the spleen and the cessation of abnormally increased breakdown of blood.

In mild cases, the disease can have the effect of almost only a cosmetic defect (as they say, such “patients are more jaundiced than sick”), in moderate cases the disease leads to loss of ability to work, especially since physical fatigue undoubtedly increases the breakdown of blood in these patients; in rare cases, hemolytic jaundice is immediate cause death - from severe anemia, consequences of splenic infarction, halemia with obstructive jaundice, etc.

Diagnosis and differential diagnosis of hemolytic anemia

You should think more often about familial hemolytic jaundice, since many cases have long been incorrectly interpreted as persistent malaria, malignant anemia, etc.

In malaria, increased blood breakdown accompanies only periods of active infection, when plasmodia are easily detected in the blood, and there is leukopenia with neutropenia; reticulocytosis is also observed periodically, only after febrile paroxysms; osmotic resistance and erythrocyte size are not reduced.

At malignant anemia the increase in blood bilirubin generally lags behind the degree of anemia, the enlargement of the spleen is less constant, patients are usually elderly, there is glossitis, achylia, diarrhea, paresthesia and other signs of funicular myelosis.

Sometimes physiological deposition of fat on the conjunctiva (pinguecula) or individual yellowish skin color in healthy individuals, etc. are mistaken for hemolytic jaundice.

Treatment of hemolytic anemia

Acute hemolytic crisis - discontinuation of the “provoking” medication; forced diuresis; hemodialysis (for acute renal failure).

Therapy for AIHA with warm antibodies is carried out with prednisolone orally for 10-14 days with gradual withdrawal over 3 months. Splenectomy - in case of insufficient effect of prednisolone therapy, relapse of hemolysis. If prednisolone therapy and splenectomy are ineffective, cytostatic therapy is used.

When treating AIHA with cold antibodies, hypothermia should be avoided and immunosuppressive therapy is used.

Of great importance is a gentle regimen with the correct alternation of work and rest, staying in a warm climate, and preventing accidental, even mild infections. Treatment with iron and liver is ineffective. Blood transfusions sometimes lead to severe reactions, but when used with carefully selected single-group fresh blood, they can be usefully used in patients with significant anemia.

In cases with a progressive increase in anemia, significant weakness, frequent hemolytic crises, making patients incapacitated and often bed sick, an operation to remove the spleen is indicated, which quickly leads to the disappearance of jaundice that has lasted for years, an improvement in blood composition, and a clear increase in performance. The operation of splenectomy is, of course, a serious intervention in itself, so the indications for it should be seriously weighed. The operation is complicated by the presence of a large spleen, with extensive adhesions to the diaphragm and other organs.

Only as an exception, after removal of the spleen, increased breakdown of the blood may again occur, and a leukemoid reaction may be observed in the white blood. Reduced osmotic resistance of erythrocytes and microspherocytosis usually remain in splenectomized patients.

Other forms of hemolytic anemia

Hemolytic anemias are observed as a symptom of a number of blood diseases or infections (for example, with malignant anemia, malaria, which are mentioned above in the section differential diagnosis familial hemolytic jaundice).

Rapidly advancing hemolysis is of serious clinical importance, leading to the same clinical picture of hemoglobinemia, hemoglobinuria and kidney complications, in various painful forms. Hemoglobinuria is observed, as an exception, periodically "and with classic familial hemolytic jaundice, and also sometimes with a special form of chronic hemolytic anemia with attacks of nocturnal hemoglobinuria and with severe atypical acute hemolytic anemia accompanied by fever (the so-called acute hemolytic anemia) without microcytosis, with fibrosis spleen and reticulocytosis up to 90-95%.

It is believed that in general, if at least 1/50 of all blood quickly breaks down, then the reticuloendothelium does not have time to completely process hemoglobin and bilirubin and hemoglobinemia and hemoglobinuria occur, along with hemolytic jaundice developing simultaneously.

Acute hemolytic anemia with hemoglobinuria and anuria after transfusion of incompatible blood (due to hemolysis of donor red blood cells) develops as follows.
Already in the process of blood transfusion, the patient complains of pain in the lower back, in the head, with a feeling of swelling, “fullness” of the head, shortness of breath, and tightness in the chest. Nausea, vomiting, stunning chills with increased temperature occur, the face is hyperemic, with a cyanotic tint, bradycardia, followed by a frequent, thread-like pulse with other signs of vascular collapse. Already the first portions of urine the color of black coffee (hemoglobinuria); anuria soon sets in; jaundice develops by the end of the day.

In the coming days, up to a week, a period of latency, or symptomatic improvement, begins: the temperature drops, appetite returns, restful sleep; jaundice disappears in the coming days. However, little urine is excreted or complete anuria continues.

In the second week, fatal uremia develops with high levels of nitrogenous waste in the blood, sometimes even with restored diuresis with impaired renal function.
Such phenomena are observed when transfusion is usually 300-500 ml of incompatible blood; in the most severe cases, death occurs already in the early shock period; with transfusion of less than 300 ml of blood, recovery occurs more often.

Treatment. Repeated transfusion of 200-300 ml of known compatible, better than that one same group, fresh blood (which is believed to eliminate the destructive spasm renal arteries), administration of alkalis and large amounts of liquid to prevent blockage of the renal tubules with hemoglobin detritus, novocaine blockade of perinephric fiber, diathermy of the renal area, liver preparations, calcium salts, symptomatic remedies, general warming of the body.

Other forms of hemoglobinuria are also known, usually occurring in separate paroxysms (attacks):

• malarial hemoglobinuric fever, occurring in patients with malaria after taking quinine in rare cases acquired hypersensitivity to him;
• paroxysmal hemoglobinuria, occurring under the influence of cooling - from special “Cold” autohemolysins; with this disease, blood cooled in a test tube to 5° for 10 minutes and again heated to body temperature undergoes hemolysis, and this is especially easy when adding fresh complement from a guinea pig; before the disease associated with syphilitic infection, which is not justified for most cases of the disease;
• March hemoglobinuria after long treks;
• myohemoglobinuria due to the excretion of myohemoglobin in the urine during traumatic crushing of muscles, for example, limbs;
• toxic hemoglobinuria in case of poisoning with Berthollet salt, sulfonamide and other chemotherapy drugs, morels, snake venom etc.

In milder cases, the case does not reach hemoglobinuria, only toxic anemia and hemolytic jaundice.

Treatment carried out according to the above principles, taking into account the characteristics of each painful form and individual characteristics sick.

Hemolytic anemia is independent disease blood or a pathological condition of the body in which the destruction of red blood cells circulating in the blood occurs through various mechanisms.

At normal functioning The natural breakdown of red blood cells is observed 3–4 months after their birth. With hemolytic anemia, the decay process is significantly accelerated and takes only 12–14 days. In this article we will talk about the causes of this disease and the treatment of this difficult disease.

What is hemolytic anemia

Hemolytic anemia is anemia caused by a disorder life cycle erythrocytes, namely the predominance of the processes of their destruction (erythrocytolysis) over formation and maturation (erythropoiesis). Red blood cells are the most numerous type of human blood cell.

The main function of red blood cells is the transport of oxygen and carbon monoxide. These cells contain hemoglobin, a protein involved in metabolic processes.

Human red blood cells function in the blood for a maximum of 120 days, with an average of 60-90 days. Aging of erythrocytes is associated with a decrease in the formation of ATP in the erythrocyte during the metabolism of glucose in this blood cell

The destruction of red blood cells occurs constantly and is called hemolysis. The released hemoglobin breaks down into heme and globin. Globin is a protein that returns to the red bone marrow and serves as material for the construction of new red blood cells, and iron is separated from heme (also reused) and indirect bilirubin.

The red blood cell count can be determined using a blood test, which is performed during routine medical check-ups.

According to world statistics, in the structure of morbidity among blood pathologies, hemolytic conditions account for at least 5%, of which hereditary types of hemolytic anemia predominate.

Classification

Hemolytic anemias are classified into congenital and acquired.

Congenital (hereditary)

Due to the impact of negative genetic factors hereditary hemolytic anemia develops on red blood cells.

IN currently There are four subtypes of the disease:

• nonspherocytic hemolytic anemia. In this case, the cause of destruction of red blood cells is the defective activity of the enzymes responsible for their life cycle;
• hemolytic anemia of Minkowski-Choffard, or microspherocytic. The disease develops due to mutations in the genes responsible for the formation of proteins that make up the walls of red blood cells.
• erythrocyte membraneopathy - increased breakdown is associated with a genetically determined defect in their membrane;
• thalassemia. This group of hemolytic anemias occurs due to a disruption in the process of hemoglobin production.

Purchased

Occurs at any age. The disease develops gradually, but sometimes begins with an acute hemolytic crisis. Patients' complaints are usually the same as with congenital form and are associated mainly with increasing .

• Jaundice is mostly mild, sometimes only subictericity of the skin and sclera is noted.
• The spleen is enlarged, often dense and painful.
• In some cases, the liver is enlarged.

Unlike hereditary ones, acquired hemolytic anemias develop in a healthy body due to the impact of any external causes on red blood cells:

Hemolytic anemia can be congenital or acquired, and in half of the cases – idiopathic, that is, having an unclear origin when doctors cannot determine exact reason development of the disease.

There are quite a few factors that provoke the development of hemolytic anemia:

In some cases, it is not possible to establish the cause of the development of acquired hemolytic anemia. This hemolytic anemia is called idiopathic.

Symptoms of hemolytic anemia in adults

The symptoms of the disease are quite extensive and largely depend on the cause that caused this or that type of hemolytic anemia. The disease can manifest itself only during periods of crisis, and does not manifest itself in any way outside of exacerbations.

Signs of hemolytic anemia occur only when there is a clear imbalance between proliferation blood cells erythrocyte series and destruction of red blood cells in the circulating blood stream, while the compensatory function of the bone marrow is depleted.

Classic symptoms of hemolytic anemia develop only with intracellular hemolysis of red blood cells and are represented by anemic, icteric syndromes and splenomegaly.

Hemolytic anemias (sickle-shaped, autoimmune, non-spherocytic and others) are characterized by the following symptoms:

• hyperthermia syndrome. More often this symptom manifests itself with the progression of hemolytic anemia in children. Temperatures increase to 38 degrees;
• jaundice syndrome. It is associated with increased breakdown of red blood cells, as a result of which the liver is forced to process an excess amount of indirect bilirubin, which enters the intestines in bound form, which causes an increase in the level of urobilin and stercobilin. Coloring occurs in yellow skin and mucous membranes.
• Anemia syndrome. This is a clinical and hematological syndrome characterized by a decrease in hemoglobin content per unit volume of blood.
• Hepatosplenomegaly is a fairly common syndrome accompanying various diseases and characterized by an increase in the size of the liver and spleen. Find out,

Other symptoms of hemolytic anemia:

• Pain in the abdomen and bones;
• Presence of signs of intrauterine development disorders in children (disproportional characteristics of various body segments, developmental defects);
• Loose stools;
• Pain in the projection of the kidneys;
• Chest pain resembling myocardial infarction.

Signs of hemolytic anemia:

Kinds	Description and symptoms
Nonspherocytic hemolytic anemia	The clinical picture of non-spherocytic hemolytic anemia is close to the clinical picture observed in the hereditary spherocytic form of the disease, i.e., patients have more or less pronounced jaundice, hepatosplenomegaly, and anemia. The majority of patients showed abnormalities in the state of the cardiovascular system. Hemosiderin crystals were often found in the urine, indicating the presence of mixed type hemolysis of erythrocytes, occurring both intracellularly and intravascularly.
Microspherocytic	The disease is congenital and is transmitted in an autosomal dominant manner. The incidence rate is the same among men and women. Another name is Minkowski-Choffard disease or hereditary spherocytosis. Sequence of symptoms: jaundice, splenomegaly, anemia. There may be an enlarged liver, symptoms of cholelithiasis, increased levels of stercobilin and urobilin.
Sickle cell	Sickle cell anemia is a hereditary hemoglobinopathy associated with a disorder in the structure of the hemoglobin protein in which it acquires a special crystalline structure - the so-called hemoglobin S. In a healthy person, it is represented by type A.
Thalassemia	This is not just one, but a whole group of hereditary blood diseases that have recessive inheritance. That is, the child will receive it if both parents pass on the diseased gene to him. In this case, they say that there is homozygous thalassemia. The disease is characterized by disruption of the production of hemoglobin, which plays a major role in the transport of oxygen throughout the body. Some people with thalassemia minor notice minor symptoms. Symptoms: Slow growth and delayed puberty Bone problems Enlarged spleen
Autoimmune	Autoimmune hemolytic anemia includes forms of the disease associated with the formation of antibodies to self-antigens of red blood cells. According to the clinical picture, two forms of the disease are distinguished: acute and chronic. In the first form, patients suddenly experience severe weakness, fever, shortness of breath, palpitations, and jaundice. In the second form, shortness of breath, weakness and palpitations may be absent or mild.
Toxic hemolytic anemia	Belongs to the group of hemolytic anemias caused by the action of chemical or medicinal agents on red blood cells.
Membranopathy	This pathological condition, in which there are defects in the membrane of red blood cells.
Traumatic anemias	Mechanical destruction of particles occurs when red blood cells collide with insurmountable obstacles. This phenomenon is possible when acute glomerulonephritis, bleeding disorders, the presence of foreign bodies in the form artificial valves hearts.

How does hemolytic anemia occur in children?

Hemolytic anemias are groups of different diseases in terms of their nature, but united by a single symptom - hemolysis of red blood cells. Hemolysis (damage) occurs in important organs: liver, spleen and medulla bones.

The first symptoms of anemia are not specific and are often ignored. A child’s rapid fatigue, irritability, and tearfulness are attributed to stress, excessive emotionality, or character traits.

Children diagnosed with hemolytic anemia are prone to infectious diseases, often such children are included in the group of frequently ill people.

With anemia in children, pale skin is observed, which also occurs when there is insufficient blood filling vascular bed, kidney diseases, tuberculosis intoxication.

The main difference between true anemia and pseudoanemia is the color of the mucous membranes: with true anemia, the mucous membranes become pale, with pseudoanemia they remain pink (the color of the conjunctiva is assessed).

The course and prognosis depend on the form and severity of the disease, on the timeliness and correctness of treatment, and on the degree of immunological deficiency.

Complications

Hemolytic anemia can be complicated by anemic coma. Also sometimes added to the overall clinical picture:

• Low blood pressure.
• Decreased amount of urine excreted.
• Cholelithiasis.

In some patients, sharp deterioration cold causes the condition. It is clear that such people are advised to stay warm all the time.

Diagnostics

When weakness, pale skin, heaviness in the right hypochondrium and others appear nonspecific symptoms you need to see a therapist and get tested general analysis blood. Confirmation of the diagnosis of hemolytic anemia and treatment of patients is carried out by a hematologist.

Determining the form of hemolytic anemia based on an analysis of the causes, symptoms and objective data is the responsibility 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.
• Splenoid and confirmed by ultrasound of the liver and spleen.

What tests need to be taken?

• General blood analysis
• Total bilirubin in the blood
• Hemoglobin
• Red blood cells

Comprehensive diagnostics of hemolytic anemias will include next research of the affected organism:

• collecting anamnesis data, studying the complaints of a clinical patient;
• blood test to determine the concentration of red blood cells and hemoglobin;
• determination of unconjugated bilirubin;
• Coombs test, especially if blood transfusion with healthy red blood cells is necessary;
• bone marrow puncture;
• determination of serum iron level by laboratory method;
• Ultrasound of the peritoneal organs;
• study of the shape of red blood cells.

Treatment of hemolytic anemia

Various forms of hemolytic anemia have their own characteristics and approaches to treatment.

The pathology treatment plan usually includes the following activities:

1. prescribing medications containing vitamin B12 and folic acid;
2. blood transfusion of washed red blood cells. This treatment method is used if the concentration of red blood cells decreases to critical levels;
3. transfusion of plasma and human immunoglobulin;
4. for elimination unpleasant symptoms and normalization of the size of the liver and spleen, it is indicated to use glucocorticoid hormones. The dosage of these medications is prescribed only by a doctor based on general condition the patient, as well as the severity of his illness;
5. for autoimmune hemolytic anemia, the treatment plan is supplemented with cytostatics; sometimes doctors resort to operational techniques treatment of the disease. The most common procedure is splenectomy.

The prognosis depends on the cause and severity of the disease.

Any hemolytic anemia, the fight against which was started untimely - complex problem. It is unacceptable to try to deal with it on your own. Her treatment must be comprehensive and prescribed exclusively qualified specialist based thorough examination patient.

Prevention

Prevention of hemolytic anemia is divided into primary and secondary.

1. Primary prevention involves measures to prevent the occurrence of hemolytic anemia;
2. Secondary – reduction clinical manifestations a pre-existing disease.

Only possible way prevent the development of anemia - maintaining a healthy lifestyle, timely treatment and prevention of other diseases.