Acquired hemolytic anemia. Hereditary hemolytic anemias
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 . If the properties of an erythrocyte are disrupted or its environment changes, it is prematurely destroyed in the bloodstream or in the reticulohistiocytic system various organs, especially the spleen.
Classification of hemolytic anemias
Usually, hereditary and acquired hemolytic anemias are distinguished, since they have different mechanisms of development and differ in their 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 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 necessary elements 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, scleral hysteria appears and skin. 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 metabolism 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 disease development
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 cholelithiasis diagnosed in the patient or his relatives at a young age (hyperbilirubinemia can contribute to 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 medical history, physical and laboratory results 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, 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.
Hemolytic anemia– this is a clinical and hematological symptom complex that arises as a result of a shortening of the duration of functioning of red blood cells, due to their increased breakdown. This pathology combines a group of hereditary and acquired diseases, the pathogenesis of which is dominated by signs of hemolysis of erythrocytes without a decrease in hemoglobin in the peripheral blood. 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.
Signs of hemolytic anemia occur only when there is a clear imbalance between the proliferation of red blood cells and the destruction of red blood cells in the circulating blood stream, while the compensatory function of the bone marrow (increased proliferation of reticulocytes) is depleted.
Autoimmune hemolytic anemia
The main provoking factor in the occurrence of autoimmune hemolytic anemia is the synthesis of antibodies to its own red blood cells, which the body perceives as foreign antigens. The manifestation of autoimmune hemolytic anemia occurs against the background of any symptomatic disease as a complication ( systemic diseases connective tissue, hemoblastosis, chronic aggressive hepatitis, nonspecific ulcerative, malignant neoplasms) or as an independent nosological unit.
Despite the rapid development of medicine in the field of diagnostic measures for blood diseases, to this day it is not possible to establish a reliable cause for the development of autoimmune hemolytic anemia.
All clinical manifestations of autoimmune hemolytic anemia do not depend on the etiological factor. Most often, patients experience a slowly progressive course of the disease. The first manifestations of the disease are general weakness, aching pain in the joints, low-grade body temperature, and abdominal pain. An objective examination of the patient reveals marked pallor and pastiness of the skin, gradually increasing jaundice, and an increase in the size of the spleen and liver.
In 50% of cases, patients experience acute hemolytic anemia of an autoimmune nature, which is characterized by a sudden onset of the disease and a violent clinical picture. In this situation, the patient’s numerous complaints come to the fore in the absence of any changes during an objective examination of the patient. The main complaints that the patient presents are: severe weakness and reduced performance, rapid heartbeat, a feeling of lack of air, an increase in body temperature to 38-39 degrees Celsius, and nausea and vomiting not associated with food intake, girdle aching pain in the upper abdomen . External manifestations hemolysis is only an increasing yellowness of the skin in the absence of an increase in the size of the liver and spleen.
Signs of autoimmune hemolytic anemia in laboratory research blood are: high reticulocytosis 200-300%, decreased number of red blood cells with a normal color index, slight leukocytosis, platelet count is not changed or slightly reduced. An absolute indicator of the autoimmune nature of anemia is an increase in ESR to high numbers. In some cases, it is possible to identify microspherocytes or fragmented red blood cells. A biochemical blood test reveals an increase indirect bilirubin, hypergammaglobulinemia. To determine the presence of antibodies on red blood cells, a specific Coombs test is performed, which becomes sharply positive in autoimmune hemolytic anemia.
The prognosis for life and performance in autoimmune hemolytic anemia depends on the course, severity and effectiveness of therapy for the underlying disease that caused the development of hemolysis. As a rule, complete recovery and restoration of working capacity cannot be achieved with any treatment method. Persistent remission is observed only after radical splenectomy and a long course of hormonal therapy.
Causes of hemolytic anemia
The cause of hemolysis of red blood cells can be any somatic disease and in such a situation acquired hemolytic anemia develops.
When exposed to one or another etiological factor, a clinical picture of an acute or chronic hemolytic condition develops.
The chronic course of hemolytic anemia is observed with paroxysmal nocturnal hemoglobinuria and cold hemoglobinuria.
Hemolytic anemia symptoms
Classic symptoms of hemolytic anemia develop only with intracellular hemolysis of red blood cells and are represented by anemic, icteric syndromes and splenomegaly.
The degree of manifestation of clinical symptoms, indicating the development of an anemic condition, directly depends on the rate of destruction of red blood cells and the compensatory reaction of the bone marrow, as the main hematopoietic organ. Signs of anemia develop only in a situation when the lifespan of red blood cells is reduced to 15 days, instead of 120 days.
According to the course, latent (compensated), chronic (with pronounced anemization) and crisis hemolytic anemia are distinguished. During a crisis course of the disease, the patient’s general condition is severe, regardless of the type of hemolysis (intravascular or intracellular).
During an exacerbation, hemolytic anemia manifests itself in the form of severe weakness, decreased performance, dizziness, difficulty breathing, increased heart rate, nagging pain in the right and left hypochondrium. A characteristic feature Acute hemolytic anemia is considered to be icterus of the skin, mucous membrane of the soft palate and sclera. Upon objective examination of the patient, in 70% of cases there is an enlargement of the spleen and protrusion of the liver from under the costal arch by more than 2 cm.
Due to thickening and stagnation of bile, the formation of stones in the gallbladder is provoked and bile ducts, therefore, patients suffering from hemolytic anemia often present with complaints characteristic of hepatitis, cholecystitis and cholangitis ( sharp pain in the right hypochondrium, nausea, vomiting, chills, short-term increase in body temperature).
In the human body, physiological erythrocyte hemolysis constantly occurs in the spleen. During the destruction of hemoglobin, indirect bilirubin is released into the circulating blood stream, which subsequently undergoes changes in structure and composition in the liver, gall bladder and intestines. The excretion of the resulting urobilin and stercobilin occurs together with urine and feces, as a result of which patients often note darkening of urine and light feces.
In a situation where intravascular destruction of red blood cells occurs, the symptoms of anemic syndrome come to the fore, while jaundice and splenomegaly are extremely rare. This type of hemolytic anemia is characterized by a crisis course of the disease, significantly worsening the patient’s condition. Characteristic symptoms of a hemolytic crisis are: general weakness, throbbing headache, feeling of lack of air, increased heart rate, uncontrollable vomiting not associated with food intake, shingles. aching pain in the upper quadrants of the abdomen and lumbar region, fever, dark brown urine. In the absence of adequate therapy, the acute clinical picture develops rapidly. renal failure, which causes death.
Laboratory signs of hemolytic anemia are: normochromic, hyperregenerative and changes in the shape and size of red blood cells (sickle-shaped, oval, microspherocytes, target-shaped). Characteristic changes in autoimmune hemolytic anemia are leukocytosis with shift leukocyte formula to the left and sharply increased ESR. Bone marrow puncture reveals hyperplasia of the red line and a pronounced erythroblastic reaction.
Hemolytic anemia in children
In childhood, both congenital and acquired forms of hemolytic anemia are observed. All hemolytic anemias have common clinical symptoms, but require identification accurate diagnosis indicating the form of anemia, since further treatment tactics and monitoring of the patient depend on this.
Congenital hemolytic anemia, fortunately, is a rare disease and accounts for no more than 2 cases per 100,000 population, however, children suffering from this form of anemia should be treated with extreme caution, since treatment of such patients is extremely difficult.
Hereditary hemolytic anemia of Minkowski-Choffard is caused by the manifestation of a defective gene, inherited in an autosomal dominant manner, causing changes in the shape of red blood cells. The shape changes as a result of disruption of the cell membrane, due to which it becomes permeable to the penetration of excess sodium ions, thereby causing swelling of the red blood cell. Excessive hemolysis of such altered red blood cells occurs outside the splenic pulp.
The onset of the disease is observed in early childhood and the first manifestations are icterus of the mucous membranes and skin. The distinctive features of this form of hemolytic anemia are the combination of severe anemic syndrome with developmental anomalies (dolichocephalic skull shape, saddle nose, high location of the hard palate).
The main criteria for establishing a diagnosis of “hereditary Minkowski-Choffard anemia” are: normochromic, hyperregenerative anemia, erythrocyte microspherocytosis, decreased osmotic resistance of erythrocytes, increased indirect bilirubin in the blood, increased size of the spleen.
The prognosis for life and health is favorable with this form of anemia and occurs only after radical splenectomy.
Another form of hereditary hemolytic anemia that occurs in childhood is anemia caused by a lack of G-6-FDG activity, which is characterized by an autosomal recessive mode of inheritance.
A characteristic sign of this pathology is the occurrence of spontaneous intravascular hemolysis after taking certain groups medicines(sulfonamides, quinine derivatives, antiplatelet agents, chloramphenicol, tubazide) or consumption of legumes.
Clinical manifestations occur 2-3 days after using the drug and manifest themselves in the form of severe weakness, nausea and vomiting, increased heart rate, febrile fever, anuria and acute renal failure. The distinctive features of this form of hereditary hemolytic anemia are hemoglobinuria and hemosiderinuria.
Characteristic changes in peripheral blood parameters are: a decrease in the number of erythrocytes and high reticulocytosis, the presence of Heinz bodies in the erythrocyte during supravital staining, an increase in the osmotic resistance of erythrocytes. In the bone marrow punctate, a hyperplastic red germ of hematopoiesis is determined.
This type of anemia is characterized by a crisis course, therefore, as preventive measures, the child must completely exclude legumes from the diet, and also avoid the use of risk group medications. Due to the fact that hereditary anemia often occurs with the development of a fulminant hemolytic crisis, accompanied by acute renal failure, the prognosis for the life and health of the child in this case is unfavorable.
The most common form of hereditary hemolytic anemia in childhood is in which the red blood cell contains pathologically excess globin, which promotes accelerated aggregation and destruction of red blood cells not only in the spleen, but also in the bone marrow.
The first manifestations of thalassemia are observed already in the neonatal period and are manifested by severe anemic syndrome, jaundice and splenomegaly in combination with developmental anomalies (square shape of the skull, protruding zygomatic arch, Mongoloid type of face, flattening of the bridge of the nose). Children suffering from thalassemia experience delays not only in physical but also in psychomotor development.
Characteristic laboratory signs thalassemia in children are: severe anemia (decrease in hemoglobin level less than 30 g/l), hypochromia (decrease in color index below 0.5), reticulocytosis, target-shaped erythrocytes when examining a smear, increased osmotic resistance of erythrocytes, high level of indirect bilirubin. The absolute criterion for diagnosing thalassemia is increased level fetal hemoglobin (more than 30%).
Thalassemia is a constantly progressive pathology, which is not characterized by periods of remission, and therefore the mortality rate for this disease is very high.
Hemolytic anemia treatment
In order to achieve maximum positive result from the treatment of hemolytic anemia, first of all, every effort must be made to reliably clarify the form of this disease, since each treatment regimen must be etiopathogenetically determined.
Thus, radical splenectomy is used as a priority treatment method for hereditary microspherocytic hemolytic anemia. Absolute indications for splenectomy are considered: a crisis course of the disease with frequent periods of exacerbation, a pronounced degree of anemia and hepatic colic. In most cases, after splenectomy, 100% remission is observed without relapses of the disease, even despite the presence of microspherocytes in the blood. In a situation where hemolysis is accompanied by the appearance of stones in the gallbladder, it is recommended to combine splenectomy with cholecystectomy.
As preventive measures, patients are recommended to take long-term choleretic (Allochol 1 tablet with each meal), antispasmodic (Riabal 1 capsule 2 times a day), and periodic duodenal intubation. In situations where there is a pronounced degree of anemia, it is advisable to use symptomatic exchange transfusion of red blood cells, taking into account the group affiliation.
In cases of hereditary hemolytic anemia caused by a G-6-FDG defect, detoxification therapy (200 ml of isotonic sodium chloride solution intravenously) is recommended, as well as preventive measures to prevent DIC syndrome (Heparin 5000 IU subcutaneously 4 times a day).
Autoimmune hemolytic anemia responds well to treatment with hormonal drugs, which are used not only to relieve a hemolytic crisis, but also as a long-term treatment. To determine the optimal dosage of Prednisolone, it is necessary to take into account general health patient, as well as peripheral blood parameters. An adequate daily dose of Prednisolone in this situation is considered to be 1 mg/kg of body weight, but if there is no effect, it is permissible to increase the dose to 2.5 mg/kg.
In situations where autoimmune hemolytic anemia occurs in severe form, it is advisable to combine detoxification therapy (Neohemodez 200 ml intravenous drip) with red blood cell transfusion, taking into account the group affiliation. Radical splenectomy is used only if there is no effect from the use of conservative therapy and should be accompanied by a prescription cytostatic drugs(Cyclophosphamide 100 mg once a day, Azathioprine daily dose 200 mg). It should be taken into account that an absolute contraindication to the use of cytostatic drugs is childhood, since drugs in this group can cause a mutagenic effect.
Separately, we should dwell on such a treatment method as transfusion of thawed or washed red blood cells. Red blood cell transfusion should be justified by the severity of the anemic syndrome and general condition patient and it is imperative to evaluate the patient’s response to the blood transfusion. Very often, patients who have undergone repeated red blood cell transfusions experience post-transfusion reactions, which are the reason for individual blood selection using an indirect Coombs test.
In some cases, hemolytic anemia responds well to treatment with the use of anabolic hormonal drugs (Retabolil 25 mg intramuscularly, Nerobol 5 mg once a day). As symptomatic therapy appropriate use antioxidant drugs(vitamins E 10 mg intramuscularly), and with concomitant iron deficiency - oral iron-containing drugs (Ferrum-Lek 10 ml 1 time / day).
It is a disease of the blood system, which can have various forms. The most dangerous of them include hemolytic anemia. The cause of this disease is the short life cycle of red blood cells. The pathological process can have several types, according to which treatment is selected.
What is hemolytic anemia?
The hemolytic form of the disease occurs against the background of a disorder life cycle red blood cells The incidence of this disease in people directly depends on their age and the continent on which they live. According to research, it can be concluded that the pathological process develops in only one percent of people.The disease may be hereditary or acquired. The first type of disease is more common. The appearance of the first signs of pathology is observed only when there is a clear imbalance between the death and formation of new blood cells.
Types of disease
The disease can have hereditary and acquired forms. Both groups can be divided into several varieties. Among the hereditary forms there are:- Thalassemia. The occurrence of this disease is diagnosed when the production of hemoglobin is impaired.
- Non-spherocytic anemia. The destruction of red blood cells occurs against the background of defective activity of enzymes that are responsible for their life cycle.
- Microspherocytic anemia. The disease occurs due to the transmission of mutated genes that must synthesize the proteins of the molecules that form the walls of red blood cells. During the course of this form of the disease, there is a decrease in activity and resistance to the loss of its shape by red blood cells.
- . The disease appears when there is a mutation in the genes that encode the sequence of amino acids responsible for the production of hemoglobin. During the course of the pathological condition, red blood cells are deformed into a sickle shape. When cells are damaged, it is impossible for them to change their shape, which leads to their increased destruction.
- Autoimmune anemia. When antibodies form and accumulate on the membranes of erythrocytes, their hemolysis is observed. As a result of this, red blood cells are marked and perceived by macrophages as foreign. During the course of this disease, independent destruction of red blood cells by the immune system is observed.
- Traumatic anemia. Most often the pathological process occurs when. If the patient's capillary structure changes, this leads to the onset of the disease. Enough common cause pathology is the installation of vascular prostheses.
- Rh conflict anemia. In most cases, pathology is diagnosed if the rhesus of the mother and fetus does not match. In a woman’s body, there is a gradual production of antibodies to red blood cells, which are characterized by the presence of the Rh antigen. This leads to the formation of immune complexes and the breakdown of red blood cells.
- Acute paroxysmal nocturnal hemoglobulinemia.
- Hemolysis of red blood cells. The occurrence of this disease can be influenced by endogenous and exogenous factors.
Causes of the disease
There are many causes of hemolytic anemia. Hereditary forms diseases quite often occur in the presence of various genetic defects in the membranes of red blood cells. If the structure of hemoglobin changes, this can lead to pathological process. In the presence of these provoking factors, morpho-functional inferiority of erythrocytes is quite often observed. This is why they break down too quickly.Acquired anemia can occur with negative impact environmental factors among or during the course of various diseases. Quite often, the pathological process develops after preventive vaccination. The cause of the disease may be a post-transfusion reaction. With hemolytic disease of the fetus, this pathological condition also develops.
The onset of the disease is diagnosed with long-term use medications, which include:
- analgesics;
- sulfonamides;
- antimalarial drugs;
- derivatives of the nitrofuran series.
Intravascular hemolysis can develop due to poisoning with substances such as heavy metals, arsenic compounds, mushroom poisons, alcoholic beverages, acetic acid etc. Reason mechanical damage and damage to the corpuscles is often caused by excessive physical exertion. Pathology can develop during the course of malaria. Patients who develop malignant arterial hypertension are at risk. Sepsis and extensive burns quite often lead to the onset of the disease.
Hemolytic anemia is a rather severe pathological process that develops under the influence of a number of factors.
Symptoms and signs of the disease in adults and children
In newborns, symptoms of hemolytic anemia are observed almost immediately after their birth. This allows you to timely identify the disease and prescribe rational treatment.Most often, signs of a pathological process appear in the form jaundice syndrome. In this case, the child's skin becomes lemon yellow. The baby also experiences dark urine. In this case, no change in the color of feces is observed. When this syndrome appears, adult patients complain of itching of the skin.
Against the background of disruption of the normal structure of the mucous membranes, their pallor is observed not only in adults, but also in children . The disease is often accompanied by oxygen deprivation syndrome. Patients complain of general weakness and shortness of breath. During the examination of the patient, an increase in heart rate is observed. Muscle strength in people during the course of the pathological process is significantly reduced. During the examination of patients, it is observed enlargement of the spleen and liver. Against this background, there is heaviness in the right side.
In young patients, quite often during the course of the pathology, the body temperature suddenly rises to 38 degrees. This is explained by the maximum destruction of red blood cells. Some patients with hemolytic anemia complain of pain in the bones and abdomen. If the pathology occurs in a child even before birth, then it is accompanied by signs of disturbances in intrauterine development. Pain in the kidney area and chest quite often accompany pathology. The disease is often accompanied by loose stools.
Hemolytic anemia has a number of symptoms, and if they appear, you should contact medical Center to prescribe adequate treatment.
Diagnosis of the disease
In order to determine hemolytic anemia, it is necessary to carry out a number of diagnostic measures. Most often, a clinical blood test is performed to determine this disease. It provides information about the quality and quantity of red blood cells. With its help, you can find out about a decrease in hemoglobin concentration, acceleration of ESR, and deformation of red blood cells.Patients may be given a urine test to confirm the preliminary test. In some cases, a red bone marrow puncture is performed. Patients may also be prescribed blood biochemistry.
Diagnosis of the disease makes it possible to prescribe rational therapy to patients, which will contribute to their recovery. More information about tests for anemia and their interpretation -.
Treatment of hemolytic anemia
The disease is quite difficult to treat and requires an integrated approach. Most often, therapy for the pathological process is carried out using medications.Patients must take folic acid. Vitamin B12 is also quite effective in treating the pathological process.
Patients are prescribed blood transfusions of washed red blood cells. This procedure is carried out if red blood counts drop to a critical level.
Treatment of the pathology should be carried out with glucocorticosteroid hormones. Most often patients are prescribed:
- Dexamethasone
- Cortinefa
- Prednisolone
- Methylprednisolone
The choice of treatment method for a disease directly depends on its type, degree of development, and individual characteristics sick. That is why this procedure should be carried out by a doctor based on the diagnostic results.
Prevention of occurrence
To avoid the appearance of hemolytic anemia, it is necessary to carry out its prevention in a timely manner, which can be primary and secondary.When primary prevention the patient is advised to do everything possible to exclude the possibility of the influence of provoking factors. In this case, it is recommended to avoid places where toxic substances are contained in excessive quantities. During the course of infectious diseases, the patient must be provided with high-quality and timely treatment.
To avoid the development of hemolysis, patients are not recommended to take sulfonamides, anti-tuberculosis drugs, antimalarial drugs, antipyretics, antibacterial and painkillers.
Carrying out secondary prevention diseases is also recommended for patients. For this purpose, it is necessary to promptly treat and prevent infectious processes, against the background of which hemolytic anemia can develop. The patient also needs to undergo regular preventive examinations and undergo the necessary tests.
Hemolytic anemia is a rather complex disease that can develop in several forms. There are various provoking factors against which pathology can develop. When the first symptoms of the disease appear, a person needs to undergo diagnostics, which will make it possible to prescribe the correct treatment.
Under the name “hemolytic anemia” is a group of blood diseases characterized by a shortening of the life cycle of red blood cells - erythrocytes. For many years, the medical community has discussed the issue of the legality of using the term “anemia” in relation to similar diseases: After all, the hemoglobin level in such patients is normal. However, this name is currently used in disease classifiers.
Types and causes of hemolytic anemia
There are hereditary and acquired hemolytic anemias.
Hereditary hemolytic anemia
The first group includes anemia caused by genetically determined abnormalities: structural disorders of erythrocyte membranes (membranopathy), decreased activity of enzymes important for the viability of erythrocytes (enzymopathies), and disturbances in the structure of hemoglobin (hemoglobinopathies).
The most common hereditary hemolytic anemias are sickle cell, associated with the synthesis of “incorrect” hemoglobin, which gives the red blood cell a sickle shape, and thalassemia, which manifests itself in a slowdown in the development of hemoglobin.
Acquired hemolytic anemia
What substances can have a detrimental effect on red blood cells that cause hemolysis? Here are some of them:
- arsine (arsenous hydrogen). It is formed under industrial production conditions and enters the body by air;
- phenylhydrazine. Used in pharmaceutical production;
- toluenediamine. These compounds can be poisoned at a factory for the production of dyes and a number of polymer compounds;
- cumene hydroperoxide (hyperiz). Used in the production of fiberglass, rubber, acetone, phenol, polyester and epoxy resins.
Autoimmune hemolytic anemia occurs when the mother’s blood and fetal blood are incompatible by group and Rh factor (hemolytic anemia of newborns), as well as after blood transfusion, when the immune system’s resistance to its own red blood cells is disrupted, which it begins to perceive as antigens.
Symptoms of hemolytic anemia
Hemolytic anemia is a group of diseases in which the lifespan of red blood cells is reduced. A characteristic symptom of all hemolytic anemias is jaundice, i.e. acquisition of a yellowish color by the skin and mucous membranes. Why is this happening? During hemolysis (destruction of red blood cells), large amounts of bilirubin are released into the blood, which causes such a striking symptom. And here are the others general signs hemolytic anemias:- an increase in the size of the liver and spleen;
- increased bilirubin in the blood;
- darkening of feces and urine (urine has a characteristic “meat slop” color);
- increased body temperature, feverish conditions;
- chills.
All anemias caused by chemical poisoning are generally very similar. At first, weakness, nausea, and possible chills are noted. At this stage, rarely does anyone end up in a hospital, unless it was a mass poisoning. Then all these symptoms increase, plus pain appears in the right hypochondrium and in the pit of the stomach, fever, and purple urine. On days 2-3, jaundice and kidney failure appear.
Thalassemia
Thalassemia, which is a severe hereditary disease: deformed skull and bones, narrow eye shape, mental and physical underdevelopment, greenish tint to the skin.
Hemolytic anemia of a newborn “brings” to its involuntary owner such symptoms as ascites (accumulation of fluid in abdominal cavity), swelling, high levels of immature red blood cells and a sharp, high-pitched cry.
Diagnosis of hemolytic anemia
The main thing in the diagnosis of hemolytic anemia is the blood picture. There is a decrease (moderate) in red blood cells and hemoglobin, microspherocytosis (decreased diameter and thickening of red blood cells), reticulocytosis (appearance of immature red blood cells), decreased osmotic resistance of red blood cells, and bilirubinemia. At x-ray examination pathways spinal cord(myelography) there is an increase in hematopoiesis. Another important one diagnostic sign- enlarged spleen.
Treatment of hemolytic anemias
Hemolytic anemia (especially hereditary) is effectively treated only by splenectomy - removal of the spleen. Other treatment methods bring only temporary improvement and do not protect against relapse of the disease. Surgical intervention is recommended during the period of weakening of the disease. Complications after surgery are possible (thrombosis portal system), but are not required.
Sickle cell anemia, thalassemia
For hemolytic anemia (sickle cell, thalassemia), transfusions of red blood cells and blood substitutes are used. It is important for the patient not to provoke a hemolytic crisis by being in conditions favorable to hypoxia (thin air, low amounts of oxygen).
Autoimmune hemolytic anemia
In the treatment of autoimmune anemia, it is important to determine the factor leading to this very autoimmunization of the body. Unfortunately, this is very rarely possible, and therefore the use of drugs that would inhibit the production of antibodies and, consequently, prevent the destruction of red blood cells comes to the fore. This is (hydrocortisone, prednisolone, cortisone), adrenocorticotropic hormone, i.e. those substances that suppress the production of antibodies in the spleen. And, of course, splenectomy, which is performed if conservative treatment is ineffective. But even this does not always protect against relapses, so after surgery it is sometimes necessary to use hormonal agents.Hemolytic anemia of the newborn
As for hemolytic anemia of the newborn, in order to prevent it, careful monitoring of the presence of antibodies in the mother is carried out. All pregnant women who are Rh negative should have regular blood tests. If antibodies are detected, the woman is admitted to a hospital, where she is given anti-Rhesus immunoglobulins.
HEREDITARY HEMOLYTIC ANEMIA ASSOCIATED WITH DISORDERS IN THE STRUCTURE OF THE RED CELL MEMBRANE
Microspherocytic hemolytic anemia (Minkowski-Choffard disease)
It is inherited in an autosomal dominant manner; the heterozygous form is more common. Distributed almost everywhere, in all racial groups. Most often, the disease manifests itself at the age of 3-15 years, but often Clinical signs are detected in the neonatal period. Sporadic forms of microspherocytic anemia may occur.
Pathogenesis. In microspherocytosis, various defects in the composition or function of red blood cell membrane proteins have been described. A hereditary defect in the erythrocyte membrane increases its permeability to sodium and water ions, which ultimately changes the volume of the cell. The most common autosomal dominant form is associated with a defect in the interaction of spectrin with ankyrin and protein 4.2, or a deficiency of protein 4.2, or a combined deficiency of ankyrin and spectrin.
Weak interaction of transmembrane proteins can lead to membrane fragmentation, a decrease in membrane surface area, an increase in its permeability, and an increase in osmotically active substances. Thus, hereditary spherocytosis is the result of a defect in any protein involved in the formation of the vertical interaction of the internal cytoskeleton, formed on spectrin, with transmembrane proteins.
Violation of the cytoskeleton leads to partial loss of the membrane, a decrease in the surface area of the erythrocyte, which is accompanied by a decrease in the size of the erythrocyte and transformation of the cell into a microspherocyte. Circulating microspherocytes have a low life expectancy (up to 12-14 days), reduced osmotic and mechanical resistance. After 2-3 passages through the spleen, the spherocyte undergoes phagocytosis by macrophages (intracellular hemolysis). Secondary splenomegaly develops, which aggravates the hemolytic process.
After splenectomy, the residence time of spherocytes in the blood increases significantly.
Clinical picture. The main symptom of the disease is hemolytic syndrome, which is manifested by jaundice, splenomegaly and anemia. Depending on the form of inheritance of the pathology (homo- or heterozygous transmission), the disease can be detected in early childhood or in later periods of life. When the disease occurs in childhood, the normal development of the body is disrupted, as a result, pronounced clinical signs are observed: skeletal deformation (especially of the skull), early enlargement of the spleen, general developmental retardation (splenogenic infantilism). In the heterozygous form of the disease, clinical signs are mild, but characteristic morphological changes in erythrocytes (microspherocytosis) occur. Hemolytic crisis occurs under the influence of provoking factors (infection, hypothermia, overwork, pregnancy, etc.).
Microspherocytic hemolytic anemia has chronic course, is accompanied by periodic hemolytic crises and remissions.
During a crisis, the temperature may rise, jaundice appears, the size of the spleen increases, and anemia increases. During the period of remission, signs of the disease are minor. High hemolysis and frequent hemolytic crises contribute to a rapid increase in the size of the spleen, a constant increase in the concentration of unconjugated bilirubin in the blood, and icterus of the sclera. Conditions are created for stagnation of bile in the liver, which sometimes leads to complications of hemolytic disease: the formation of pigment stones in the gall bladder (cholelithiasis), angiocholecystitis, etc. Sometimes trophic ulcers of the legs develop, healing of which is possible only after splenectomy.
Changes in the bone marrow. Bone marrow is hypercellular. Extramedullary foci of hematopoiesis develop in the spleen and other organs. Erythroblasts predominate, the number of which is 60-70% of bone marrow cells, the leukocyte/erythrocyte ratio is 1:3 or more. The maturation of erythroblasts and the release of red blood cells to the periphery proceed at an accelerated pace. With intense hematopoiesis after a severe hemolytic crisis, megaloblasts can be observed in the bone marrow, apparently as a consequence of vitamin B12 deficiency or increased consumption of folic acid. Very rarely, erythroblastopenia is detected in sternal puncture - the so-called aregenerative crisis, which is reversible.
With severe uncompensated hemolysis, the anemia is normochromic. However, anemia for a long time may be absent, but polychromatophilia and reticulocytosis are detected in the peripheral blood - signs of active bone marrow erythropoiesis. Red blood cells (microspherocytes) are characterized by a small diameter (on average 5 microns), increased thickness and normal volume. The average thickness is increased to 2.5-3.0 microns. The spherical index - the ratio of the diameter (d) of an erythrocyte to its thickness (T) - is reduced to an average of 2.7 (with the norm being 3.4-3.9). The hemoglobin content in erythrocytes is within normal limits or slightly higher. The number of microspherocytes during the period of remission and during the latent form of the disease is not high, while during the period of crisis, hemolysis can be accompanied by an increase of up to 30% or more. Microspherocytes in blood smears are small, hyperchromic, without central clearing. The erythrocyte histogram shows a deviation to the left, towards microcytes, RDW is normal or slightly increased. A feature of microspherocytic hemolytic anemia is constantly increased hemolysis, which is accompanied by reticulocytosis. During the period of hemolytic crisis, the number of reticulocytes reaches 50-80% or more, during the period of remission - does not exceed 2-4%. Reticulocytes have a large diameter with normal thickness. Erythrokaryocytes may appear. The hemolytic crisis is accompanied by a slight neutrophilic leukocytosis. The platelet germ, as a rule, is not changed. The erythrocyte sedimentation rate during a crisis is increased.
One of the characteristic signs of the disease is a decrease in the osmotic stability of red blood cells. Among patients with microspherocytic hemolytic anemia, there are patients in whom, despite obvious spherocytosis, the osmotic resistance of erythrocytes is normal. In these cases, it is necessary to study the resistance of erythrocytes to hypotonic saline solutions after preliminary incubation for two days. Splenectomy does not eliminate the reduced osmotic and mechanical stability of red blood cells.
The development of splenomegaly with hypersplenism syndrome is accompanied by leukopenia, neutropenia and often mild thrombocytopenia. There is a decrease in haptoglobin. Consequences of high hemolysis: bilirubinemia with a predominance of unconjugated bilirubin, the content of urobilinogen in the urine is increased, it has a brown-red tint, feces are sharply colored due to the large amount of stercobilinogen.
Ovalocytic hemolytic anemia(oval cell, hereditary ovalocytosis, liptocytosis)
A rare form of the disease, common in Western Africa (2%), inherited in an autosomal dominant manner. Depending on hetero- or homozygous transmission, various clinical and hematological manifestations of the disease are possible.
Pathogenesis. The disease is based on pathology of the erythrocyte membrane. It usually occurs due to a molecular defect in the membrane cytoskeletal proteins. The mechanical basis for the decrease in membrane stability is the weakening of lateral bonds between spectrin molecules (dimerdimer interaction) or a defect in the spectrin-actin-protein 4.1 complex. The most common cause (65% of cases) of hereditary ovalocytosis is a mutation leading to the replacement of amino acids in the amino-terminal part of a-spectrin. Mutations of the genes responsible for the synthesis of b-spectrin occur in approximately 30% of cases; heterozygous carriage of mutations is accompanied by diversity clinical manifestations. The lifespan of ovalocytes in the body is shortened. The disease is characterized by intracellular hemolysis with predominant destruction of red blood cells in the spleen.
Clinical picture. As an anomaly, ovalocytosis in most cases is an asymptomatic carriage without clinical manifestations, however, anemia develops in approximately 10% of patients moderate severity or even heavy. In the homozygous form, the clinical signs of ovalocytic anemia are practically no different from microspherocytosis. The disease is characterized by a chronic, mild course with hemolytic crises, accompanied by compensated or decompensated hemolysis, jaundice and anemia, the level of which depends on the compensatory capabilities of erythropoiesis. Patients are characterized by splenomegaly, constitutional changes in the skeleton (skull), possible trophic ulcers of the leg and other symptoms that can be observed with microspherocytic hemolytic anemia.
Changes in the bone marrow. Bone marrow is characterized by a regenerative or hyperregenerative type of hematopoiesis with a predominance of erythroblasts. The leukocyte/erythrocyte ratio is 1:3 or more (thanks to erythroblasts), depending on the activity of hemolysis and bone marrow hematopoiesis.
Changes in peripheral blood. The anemia is normochromic in nature with high reticulocytosis. Ovalocytes have normal average volume and hemoglobin content. The largest diameter of erythrocytes reaches 12 microns, the smallest - 2 microns. Ovalocytosis of erythrocytes can range from 10 to 40-50% of cells in heterozygous carriage and up to 96% of erythrocytes in homozygous carriage of abnormal genes. The osmotic resistance of ovalocytes is reduced, autohemolysis is increased, and the erythrocyte sedimentation rate is increased.
Ovalocytosis as a symptomatic form (with a small number of ovalocytes) can occur in various pathological conditions, mainly for hemolytic anemia, liver diseases, myelodysplastic syndrome. A combination of ovalocytosis with sickle cell anemia, thalassemia, and pernicious anemia is known. In such cases, ovalocytosis is temporary and disappears with effective therapy underlying disease. That is why only those cases in which at least 10% of red blood cells have oval shape and the pathology is hereditary.
Dental hemolytic anemia(stomatocytosis)
A rare form of the disease, inherited in an autosomal dominant manner.
Pathogenesis. The disease is based on a violation of the structural proteins of the erythrocyte membrane, leading to disruption of the regulation of cell volume. The deformability of an erythrocyte depends on the ratio of surface area and cell volume. The discoid cell has the ability to change shape and overcome the narrow spaces of capillaries, which also facilitates the exchange of oxygen in the capillaries of the lungs and peripheral tissues. A spherical cell is practically unable to change shape; it has a reduced ability to exchange oxygen with tissues. A normal red blood cell has a surface area of about 140 µm2, a volume of about 90 fl, and a hemoglobin concentration of about 330 g/l. Large membrane proteins play a decisive role in the cationic transmembrane exchange of erythrocytes and thereby regulate cell volume. These proteins include transmembrane Na\K+, Cl1-co-transporters, Na+, Cl- co-transporters, ion exchange protein-3, Na\K+-co-transporters, Na\K+-ATPase, Ca+2-ATPase etc. Impaired functioning of these proteins with the accumulation of cations inside the erythrocyte leads to the accumulation of water in it and the acquisition of cell sphericity. The anomaly of red blood cells is accompanied by increased destruction, mainly in the spleen due to intracellular hemolysis.
Clinical picture. Maybe with various manifestations- from complete compensation in carriers of the pathological gene to severe hemolytic anemia, reminiscent of microspherocytosis. Intracellular hemolysis of red blood cells is accompanied by an enlarged spleen, jaundice, a tendency to form gallstones and skeletal changes.
Changes in the bone marrow. The bone marrow is hypercellular due to the expanded red line. Indicators of bone marrow hematopoiesis depend on the severity of hemolysis and the activity of erythropoiesis. Remission may not be accompanied by anemia; during a crisis, anemia is usually of a regenerative or hyperregenerative nature.
Changes in peripheral blood. The morphological feature of the disease is stomatocytosis, which is characterized by the presence in the center of the cell of an uncolored area in the form of an elongated light stripe resembling the shape of a mouth, or a rounded shape. The volume of erythrocytes and the concentration of hemoglobin do not differ from the norm, the resistance of erythrocytes may be reduced. During severe hemolytic crises, low hemoglobin levels and a decrease in the number of red blood cells are observed. Anemia is accompanied increased content reticulocytes and unconjugated bilirubin.
Hereditary hemolytic anemia caused by a violation of the lipid structure of the erythrocyte membrane(acanthocytosis)
A rare disease, inherited in an autosomal recessive manner. Hereditary acanthocytosis is detected in abetalipoproteinemia. A decrease in the content of cholesterol, triglycerides, and phospholipids in the blood is reflected in the lipid composition of the erythrocyte membrane: the concentration of lecithin and phosphatidylcholine is reduced in them, the content of sphingomyelin is increased, the cholesterol level is normal or increased, the phospholipid content is normal or reduced. All these disturbances in the erythrocyte membrane contribute to a decrease in the fluidity of the membrane and a change in their shape. The red blood cells acquire a jagged outline similar to acanthus leaves, which is why they are called acanthocytes. Abnormal red blood cells are destroyed mainly in the spleen by intracellular hemolysis.
Clinical picture. There are signs of anemia, hemolysis of red blood cells, symptoms of lipid metabolism disorders: retinitis pigmentosa, eye nystagmus, hand tremor, ataxia.
Changes in the bone marrow. Hyperplasia of cellular elements of erythropoiesis.
Changes in peripheral blood. Normochromic normocytic anemia is observed. The main morphological feature of this form of hemolytic anemia is erythrocytes with a jagged outline (acanthocytes), which can account for up to 40-80% of erythrocytes. Reticulocytosis is noted. The osmotic resistance of red blood cells is normal or reduced. The number of leukocytes and platelets is within normal limits.
HEREDITARY HEMOLYTIC ANEMIA CAUSED BY ERYTHROCYTE ENZYME DEFICIENCY
Hemolytic anemias caused by a deficiency of erythrocyte enzymes (non-spherocytic hemolytic anemias) have a recessive type of inheritance. Clinical and hematological manifestations of the disease depend on the location of the hereditary enzyme defect in erythrocytes. Erythrocyte enzymopathies are associated with deficiency of enzymes of glycolysis (pyruvate kinase, hexokinase, glucose phosphate isomerase, triose phosphate isomerase), pentose phosphate pathway or glutathione metabolism (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and glutathione reductase). Most often, enzymopathies are associated with defects in glucose-6-phosphate dehydrogenase, pyruvate kinase or glutathione reductase. Enzymopathies with defects in other metabolic pathways are rare and have no practical significance in the occurrence of hemolytic anemia. Laboratory confirmation erythrocyte enzymopathies is based on the biochemical determination of enzyme activity in the hemolysate.
Glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase (G-6-PD) is the only enzyme of the pentose phosphate pathway, the primary deficiency of which leads to hemolytic anemia. This is the most common erythrocyte fermentopathy: about 200 million people in the world have this pathology. It prevails among the inhabitants of the Mediterranean basin, South-East Asia, India. The gene for G-6-PD synthesis is linked to the X chromosome, so the disease manifests itself much more often in men. Hemolytic anemia associated with G-6-PD deficiency is more often found in residents of Azerbaijan, Dagestan, less often in Central Asia; among Russians it is about 2%.
Provoking factors for a hemolytic crisis can be infectious diseases (influenza, salmonellosis, viral hepatitis), eating faba beans (favism), inhalation pollen. The latter is usually accompanied by a milder hemolytic crisis, but occurs within a few minutes after contact with pollen. Features of favism are acute hemolysis, which occurs faster than that caused by taking medications, and dyspeptic disorders. Hemolytic crisis can be triggered by taking certain medicines, most often antimalarial, sulfonamide, nitrofuran, anthelmintic and other drugs. Clinical symptoms may occur on the 2-3rd day from the start of taking the drug. The first symptoms are usually icterus of the sclera and dark urine. Stopping the medication prevents the development of a severe hemolytic crisis. Otherwise, on the 4-5th day a hemolytic crisis occurs with the release of black or brown urine as a result of intravascular hemolysis of red blood cells.
In severe cases of the disease, the temperature rises, headache, vomiting, and sometimes diarrhea appear. Shortness of breath and enlarged spleen occur. Intravascular hemolysis provokes activation of blood coagulation, which can lead to blockade of microcirculation in the kidneys and acute renal failure. In the bone marrow there is a sharp stimulation of erythropoiesis. There is anemia in the blood; during a crisis, the amount of hemoglobin decreases to 20-30 g/l, the number of reticulocytes and leukocytes increases with a shift in the leukocyte formula to the left to myelocytes. The platelet count usually does not change. In severe hemolytic crisis, a large number of Heinz-Ehrlich bodies may be detected as a result of precipitation of globin chains and erythrocyte membrane proteins. Anisocytosis, poikilocytosis, polychromatophilia, basophilic punctation, and Jolly bodies are noted. The content of free hemoglobin in the blood serum increases (intravascular hemolysis), the concentration of unconjugated bilirubin often increases, and hypohaptoglobinemia is observed. In the urine - hemoglobinuria, hemosiderinuria. Diagnosis is based on determining the level of the G-6-PD enzyme.
Pyruvate kinase deficiency
Pyruvate kinase at the final stage of glycolysis catalyzes the formation of adenosine triphosphate. Deficiency of pyruvate kinase can lead to a decrease in adenosine triphosphate in red blood cells and the accumulation of intermediate products of glycolysis that are formed at previous stages. Content final products glycolysis (pyruvate and lactate) decreases. A deficiency of adenosine triphosphate is accompanied by dysfunction of the erythrocyte adenosine triphosphatase pump and loss of potassium ions. A decrease in monovalent ions in the erythrocyte leads to dehydration and shrinkage of the cell, which makes it difficult for oxygenation and oxygen release by hemoglobin. At the same time, the accumulation of intermediate products of glycolysis, in particular 2,3-diphospho-glycerate, which reduces the affinity of hemoglobin for oxygen, facilitates the release of oxygen to tissues.
Clinical symptoms of the disease are observed in homozygous carriers. The disease is characterized by moderate to severe hemolytic anemia with intracellular hemolysis. Increased hemolysis is detected from birth, accompanied by frequent and severe hemolytic crises. The appearance of signs of the disease at the age of 17-30 is characterized by scant clinical symptoms in the form of icterus of the sclera and skin. Splenomegaly is observed almost constantly, sometimes in heterozygous carriers, although they usually do not have anemia. Hemolytic crisis is provoked by infection, heavy physical activity, pregnancy, hemolysis intensifies during menstruation.
In the bone marrow punctate there is pronounced erythrokaryocytosis. The most important diagnostic criterion is deficiency of pyruvate kinase activity. Pronounced clinical effects are observed in cases where the residual enzyme activity is below 30% of normal.
In the blood, in most cases, normochromic nonspherocytic anemia with slight anisocytosis and poikilocytosis occurs. The amount of hemoglobin and erythrocytes can be normal, reduced, severe anemia is also possible (Hb - 40-60 g/l), erythrocyte indices are approaching normal. Smears often reveal polychromatophilia and erythrocytes with basophilic punctation, sometimes target-like erythrocytes, erythrokaryocytes. Reticulocytosis during a crisis can reach 70%. White blood cell and platelet counts are usually normal, although in rare cases There is a combined enzyme defect of erythrocytes, leukocytes and platelets. The erythrocyte sedimentation rate during the absence of severe anemia is within normal limits. The osmotic resistance of erythrocytes does not correlate with the form of enzyme deficiency and, even with the same erythrocyte defect, can be different. In the blood serum during a hemolytic crisis, unconjugated (indirect) bilirubin is increased.
HEMOLYTIC ANEMIA ASSOCIATED WITH IMPAIRED GLOBIN SYNTHESIS (HEMOGLOBINOPATHY)
There are quantitative and qualitative hemoglobinopathies. In quantitative hemoglobinopathies, the ratio of normal globin chains is disrupted. Qualitative hemoglobinopathies are diseases in which a genetic abnormality leads to the synthesis of hemoglobin with an altered globin structure. The basis for laboratory diagnosis of qualitative and quantitative hemoglobinopathies is hemoglobin electrophoresis on cellulose acetate.
Thalassemia
A heterogeneous group of hereditary diseases, which are based on a violation of the synthesis of one of the polypeptide chains of globin, which leads to an increase in the production of other chains and the development of an imbalance between them. Thalassemias are classified as quantitative hemoglobinopathies, since the structure of hemoglobin chains is not changed. β-thalassemias are more common. Chains synthesized in excess accumulate and are deposited in bone marrow erythrocytes and peripheral blood erythrocytes, causing damage to the cell membrane and premature cell death. Erythrokaryocytes die in the spleen and bone marrow. Anemia is accompanied by a slight increase in reticulocytes. An imbalance in the synthesis of globin chains causes ineffective erythropoiesis, intracellular hemolysis of peripheral blood red blood cells - splenomegaly and hypochromic anemia varying degrees of severity.
B-Thalassemia is a heterogeneous disease. Currently, more than 100 mutations are known to cause p-thalassemia. Typically, the defect consists of the formation of defective b-globin mRNA. The variety of molecular defects leads to the fact that the so-called homozygous p-thalassemia often represents a double heterozygous state for various defects p-globin synthesis. A distinction is made between p-thalassemia, when homozygotes completely lack the synthesis of globin p-chains, and P+-thalassemia, when the synthesis of b-chains is partially preserved. Among p+ thalassemias, there are two main forms: the severe Mediterranean form, in which about 10% of the normal chain is synthesized (thalassemia major, Cooley's anemia), and the lighter, black form, when about 50% of the synthesis of the normal p-chain is preserved. The group of p-thalassemias also includes 8p-thalassemia and Hb Lepore. As a result, there are significant differences in clinical picture various forms of thalassemia, but all β-thalassemias have common features: intracellular hemolysis of red blood cells, ineffective erythropoiesis in the bone marrow and splenomegaly.
Thalassemia major (Cooley's anemia, thalassemia major). It is considered a homozygous form of thalassemia, although in many cases the disease is a double heterozygous condition for various forms p-thalassemia. Clinically, the disease manifests itself by the end of 1-2 years of a child’s life with splenomegaly, jaundice, pallor of the skin, bone changes (square skull, flattened bridge of the nose, protruding cheekbones, narrowing of the palpebral fissures). Children are physically poorly developed.
In the bone marrow, hyperplasia of the red line is observed, and a significant number of sideroblasts are detected. In the blood - hypochromic microcytic anemia, severe anisocytosis, there are erythrocytes with basophilic punctation, erythrokaryocytes, poikilocytosis, target-like erythrocytes, schizocytes. Even with severe anemia, the reticulocyte count is not high, since ineffective erythropoiesis is expressed in the bone marrow. There is an increase in the osmotic resistance of erythrocytes. Leukopenia with relative lymphocytosis is characteristic; during a hemolytic crisis - neutrophilic leukocytosis with a shift in the leukocyte formula to the left. In the blood serum there is hyperbilirubinemia due to unconjugated bilirubin, the content is increased serum iron. Excessive iron deposition leads to organ siderosis. A characteristic sign of thalassemia major is a marked increase in the concentration of fetal hemoglobin. The amount of HbA varies depending on the type of thalassemia. In homozygotes with p-thalassemia, HbA is practically absent. With p+ thalassemia (Mediterranean type), HbA varies from 10 to 25%; with p+ thalassemia of the Negro type, the HbA content is much higher. However, the severity of the disease does not always correlate with the amount of fetal hemoglobin. The HbA2 content may be different, often increased, but the HbA2/HbA ratio is always less than 1:40. The diagnosis is confirmed by hemoglobin electrophoresis (HbF level - up to 70%).
Thalassemia minor is a heterozygous form of p-thalassemia. Clinically, thalassemia minor is characterized by less pronounced symptoms than thalassemia major and can be practically asymptomatic.
In the bone marrow there is hyperplasia of the erythroid lineage, the number of sideroblasts is increased or normal. Moderate hypochromic microcytic anemia is observed in the blood: a moderate decrease in hemoglobin with normal and sometimes increased quantity erythrocytes, decreased MCV, MCH, MSHC indices. Blood smears show anisocytosis, poikilocytosis, target-like erythrocytes, there may be basophilic punctuation of erythrocytes, and reticulocytosis is detected. Unconjugated bilirubin is moderately elevated in the blood serum, and iron levels are usually normal or elevated.
The diagnosis is established based on the results of determining small fractions of hemoglobin HbA2 and HbF. Patients with the heterozygous form of p-thalassemia are characterized by an increase in the content of the HbA2 fraction to 3.5-8% and in approximately half of the patients - HbF to 2.5-7%.
A-Thalassemia occurs when there is a mutation in genes located in the 11th pair of chromosomes, encoding the synthesis of a-chains. With a deficiency of a-chains, tetramers accumulate in the blood of newborns, and HbH (P4) accumulates in the postnatal period (and in adults). There are 4 forms of a-thalassemia.
Homozygous a-thalassemia develops as a result of complete blockade of a-chain synthesis and is characterized by the absence normal hemoglobins(70-100% is Hb Bart's). Hb Bart's is not able to carry oxygen due to an abnormally increased affinity for it, as a result of which tissue anoxia occurs, leading to dropsy and intrauterine fetal death.
H-hemoglobinopathy is caused by a significant inhibition of a-chain production due to the absence of 3 out of 4 genes. Excessive synthesis of b-chains leads to their accumulation and the formation of tetramers. In newborns, 20-40% is accounted for by Hb Bart's, which later changes to HbH. HbH is functionally defective, since it has a very high affinity for oxygen, does not bind to haptoglobin, is unstable, unstable, easily oxidized and precipitated in the cell as it ages. This disease occurs. advanced education MetHb. HbH aggregation changes the elasticity of the erythrocyte membrane, disrupts cell metabolism, which is accompanied by hemolysis.
Clinically, H-hemoglobinopathy occurs in the form of thalassemia intermedia. The disease usually manifests itself towards the end of the first year of life as chronic hemolytic anemia moderate degree severity, occasionally observed asymptomatic. The disease is characterized by a relatively mild clinical course, hepatosplenomegaly, icterus, and anemia. Skeletal changes are minor. In the bone marrow there is moderate hyperplasia of the erythroid germ, slight ineffective erythropoiesis. In the blood - pronounced hypochromia and target-like erythrocytes, slight reticulocytosis. After incubation of blood with cresyl blue at 55 °C, unstable HbH precipitates in the form of many small violet-blue inclusions in the red blood cells, which distinguishes it from other forms of α-thalassemia. After splenectomy, inclusion of HbH appearance begin to resemble Heinz-Ehrlich bodies. However, in chemical structure they differ from Heinz-Ehrlich bodies in that they consist of precipitated b-chains, while Heinz-Ehrlich bodies are precipitated HbA molecules and some other unstable hemoglobins. During electrophoresis of blood serum in an alkaline buffer, an additional fraction is observed moving ahead of HbA (fast-moving fraction). In adults, HbH values are 5-30%, up to 18% may be Hb Bart's, HbA2 is reduced (1-2%), HbF is normal or slightly increased (0.3-3%).
α-thalassemia minor (a-tht) - heterozygous condition for the α-thr gene. Synthesis of α-chains is moderately reduced. Found in peripheral blood mild degree anemia with morphological changes in erythrocytes characteristic of thalassemia. In newborns who are carriers of this gene, the content of Hb Bart's in the umbilical cord blood does not exceed 5-6%. The life expectancy of erythrocytes is at the lower limit of normal.
Sickle cell anemia
Sickle cell anemia (hemoglobinopathy S) is a qualitative hemoglobinopathy. An abnormality in the structure of hemoglobin in sickle cell anemia is the replacement of the b-chain of glutamic acid with valine at position 6, which leads to increased binding of one hemoglobin molecule to another. Hemoglobinopathy S most often develops in people living in countries where malaria is common (Mediterranean, Africa, India, Central Asia). The replacement of one amino acid with another is accompanied by severe physicochemical changes in hemoglobin and leads to depolymerization of HbS. Deoxygenation causes the deposition of abnormal hemoglobin molecules in the form of monofilaments, which aggregate into oblong-shaped crystals, thereby changing the membrane and the sickle shape of red blood cells. Average duration The lifespan of red blood cells in anemia homozygous for hemoglobin S is about 17 days. At the same time, such an anomaly makes these red blood cells unsuitable for the life of plasmodia; carriers of hemoglobin S do not suffer from malaria, which, through natural selection, has led to the spread of this hemoglobinopathy in the countries of the “malarial belt”.
The homozygous form clinically manifests itself several months after birth. Characterized by severe pain in the joints, swelling of the hands, feet, legs, associated with vascular thrombosis, bone changes (tall, curved spine, tower skull, altered teeth). Aseptic necrosis of the heads of the femur and humerus, pulmonary infarction, occlusions are common cerebral vessels. Children develop hepatomegaly and splenomegaly. The disease is characterized by hemolytic crises with intravascular hemolysis, therefore a common complication There are thromboses of small and large vessels of various organs. In the blood - unexpressed normochromic anemia. During a hemolytic crisis - sharp drop hemoglobin and hematocrit, reticulocytosis, normoblastosis, Jolly bodies, sickle erythrocytes, basophilic punctation, target erythrocytes, poikilocytosis, leukocytosis, thrombocytosis, increased erythrocyte sedimentation rate, unconjugated bilirubin. Urine is black due to hemoglobinuria, hemosiderin is detected. The addition of infections can be accompanied by aplastic crisis - erythrocytopenia, reticulocytopenia, thrombo- and leukocytopenia. Sickling can be detected in a test with sodium metabisulfite or when a tourniquet is applied to the base of the finger (reduced oxygen availability). The final diagnosis is established after blood electrophoresis, where 90% HbS, 2-10% HbF, and no HbA are observed.
The heterozygous form (carriage of the sickle cell trait) is characterized by a benign course of the disease. In some patients, the only symptom may be spontaneous hematuria associated with small infarctions of the renal vessels.
Severe hypoxia develops at high altitudes. In these cases, there may be thrombotic complications. During a crisis, low levels of hemoglobin, sickle-shaped erythrocytes, and erythrokaryocytes are observed in the blood.
Hemolytic anemia caused by the carriage of abnormal stable hemoglobins C, D, E
Common forms of stable hemoglobins are C, D, E. In HbC, glutamic acid at position 6 is replaced by lysine, which leads to its crystallization; in HbE, glutamic acid at position 26 is replaced by lysine; in HbD, glutamic acid at position 121 is replaced by glutamine. Heterozygous forms occur without clinical manifestations.
In homozygotes clinical symptoms caused by anemia: mild hemolytic anemia, jaundice, splenomegaly are characteristic. The anemia is normocytic in nature; there are many target cells in the blood. There is a tendency for hemoglobin molecules to crystallize. The combination of all 3 types of hemoglobinopathies with thalassemia gives a severe clinical picture.
Hemolytic anemia caused by carriage of abnormal unstable hemoglobins
Substitution of amino acids in HbA in the a- or b-chains causes the appearance of abnormal unstable hemoglobin. Displacement at the heme attachment site causes molecular instability leading to denaturation and precipitation of hemoglobin within the red blood cell. Precipitated hemoglobin attaches to the erythrocyte membrane, which leads to the destruction of the erythrocyte, the appearance of Heinz-Ehrlich bodies, and the elasticity and permeability of the cell membrane is impaired. As red blood cells pass through the spleen, they lose part of their membrane and are then destroyed.
Clinical picture. Hemolytic anemia has been observed since childhood. Crises can be caused medicinal substances or infection. The blood shows low hemoglobin, target-shaped red blood cells, basophilic punctation, polychromasia, reticulocytosis, Heinz-Ehrlich bodies, and an increased content of erythrokaryocytes. The osmotic resistance of red blood cells is normal or slightly increased. The study of the primary structure of pathological hemoglobin allows us to determine the type of unstable hemoglobin. Abnormal hemoglobin accounts for 30-40% of the total hemoglobin.
