Hemolysis is the physiological destruction of blood cells, namely cells of the erythrocyte series, which reflects the natural process of their aging. Direct destruction of blood cells of the erythrocyte series occurs under the action of hemolysin, in the role of which most often acts as bacterial toxins.
Causes of hemolysis
Depending on the origin, all variants of the course of the hemolytic reaction can be attributed to one of two main variants: natural or pathological. Natural hemolysis is a continuous chain of chemical processes, as a result of which a "physiological renewal" of the erythrocyte composition takes place, under the condition of the normal functioning of the structures of the reticuloendothelial system.
The variants of hemolytic reactions that are observed in laboratory conditions include temperature and osmotic hemolysis. In the first type of hemolysis, the chain of hemolytic reactions is triggered by the action of critical low temperatures on the components of the blood. With osmotic hemolysis, the destruction of erythrocytes occurs when blood enters the hypotonic environment. For healthy people, the minimum osmotic resistance of erythrocytes, which is in the range of 0.48% NaCl, is typical, while the total destruction of the bulk of erythrocytes is observed at a NaCl concentration of 0.30%.
In a situation where the patient has endotoxemia due to the action of infectious microorganisms, conditions are created for the development of biological hemolysis. A similar hemolytic reaction is also observed during transfusion of incompatible whole blood or its components.
Another variant of the hemolytic reaction is the mechanical type of hemolysis, the appearance of which is facilitated by the mechanical effect on the blood (for example, shaking a tube containing blood). This variant of the hemolytic reaction is characteristic for patients who underwent prosthetic valvular apparatus of the heart.
There is a whole spectrum of substances with active hemolyzing properties, among which snake venoms and poison of insects are the most active. The development of hemolysis is promoted by the influence of a number of chemicals of the chloroform group, gasoline and even alcohol.
A rare and at the same time the most severe for the patient etiopathogenetic form of the hemolytic reaction is autoimmune hemolysis, the emergence of which is possible if the patient's body produces antibodies to its own blood cells of the erythrocyte series. This pathology is accompanied by severe anemia of the body and the release of hemoglobin in the urine at a critically high concentration.
Symptoms and signs of hemolysis
In a situation where a person does not show signs of pathological hemolysis, and the destruction of red blood cells occurs in a planned manner with the participation of the structures of the reticuloendothelial system by intracellular type, no external manifestations of hemolysis will be felt by a person.
The clinical picture of hemolysis is observed only in the case of its pathological course and includes several periods: a hemolytic crisis or acute hemolysis, a subcompensated phase of hemolysis and a period of remission.
The development of acute hemolysis, which is characterized by a fulminant course, significantly worsening the patient's health, is most often observed with transfusion of incompatible blood components, severe infectious damage to the body and toxic effects, such as medication. The danger of this condition is that the hemolytic reaction is so intense that the body lacks compensatory possibilities for the production of a sufficient number of red blood cells. In this regard, the clinical symptomatology of hemolytic crisis consists of manifestations of bilirubin intoxication and severe form of anemic syndrome. Specific signs of acute hemolytic crisis arising intraoperatively are the appearance of unmotivated excessive bleeding of the wound surface, as well as the release of dark urine through the catheter.
The manifestation of bilirubin intoxication is a change in the coloration of the skin in the form of icterism, which is diffuse intensive. In addition, the patient is concerned about severe nausea and multiple vomiting, which has no connection with food intake, a pronounced pain syndrome in the abdominal cavity region that does not have a clear localization. In severe hemolytic crisis, the patient develops a convulsive syndrome with lightning speed and various degrees of impaired consciousness.
Symptoms that are a reflection of anemic syndrome are marked weakness and inability to perform normal physical activity, visual pallor of the skin, respiratory disorders as a form of dyspnea, and with an objective examination of the patient systolic murmur is often detected in the projection of auscultation of the apex of the heart. Pathognomonic symptom of intracellular pathological hemolysis is an increase in the size of the spleen and liver, and intravascular hemolysis is characterized by a change in urine in the form of its darkening.
A specific manifestation of acute hemolysis is the appearance of specific changes in blood and urine analysis in the form of severe bilirubinemia and hemoglobinemia, thrombocytopenia and a decrease in fibrinolysis factors, hemoglobinuria and a significant increase in the creatinine and urea score.
The danger of hemolysis occurring in acute form is the possible development of complications in the form of acute cardiovascular insufficiency , DVS-syndrome , aregenerative crisis and acute renal failure.
In the subcompensatory phase of hemolysis, the processes of the generation of blood cells by the erythroid bone marrow are activated, so the severity of clinical manifestations is reduced, but skin manifestations and hepatosplenomegaly persist. Anemic syndrome in this stage of hemolysis is practically not observed, and in the clinical study of blood there is an increased number of reticulocytes, reflecting the regenerative process in the blood.
A special form of hemolytic reaction is hemolytic disease, which is observed in children during the newborn period. Even in the prenatal period, the fetus has hemolytic manifestations, caused by the incompatibility of the blood indicators of the mother and fetus. The intensity of development of the hemolysis reaction has a clear correlation dependence on the rise in the titer of antibodies in the blood of a pregnant woman.
The clinical display of hemolysis in newborns can proceed according to three classical options. The most unfavorable for the recovery of the child is a swollen version, in which the risk of stillbirth is significantly increased. In addition to the expressed puffiness of soft tissues, there is an excessive accumulation of fluid in the natural cavities (pleural, pericardium, abdominal cavity).
The icteric syndrome manifests itself in a change in the coloration of the skin, amniotic fluid and original grease. There are signs that the child has signs of toxic damage to the structures of the central nervous system in the form of increased convulsive readiness, rigidity and opisthotonus, oculomotor disorders and the "setting sun" symptom. The appearance of these symptoms can be fatal.
Anemia syndrome in a newborn child, as a rule, is not accompanied by pronounced clinical manifestations and consists only in changes in laboratory analysis. The duration of the anemic syndrome with favorable hemolysis in a newborn child, as a rule, does not exceed three months.
Types of hemolysis
Under the condition of normal functioning of all organs and systems of the human body, the processes of formation of erythrocytes and their destruction are in balance. The preferential localization of the process of destruction of erythrocyte blood cells is the structures of the reticuloendothelial system, the main representatives of which are the spleen and liver, in which fragmentation of the erythrocyte and its subsequent lysis is observed. As you age, red blood cells lose elasticity and the ability to change their own form, which makes it difficult for them to pass through the splenic sinuses. The result of this process is the retention of erythrocytes in the spleen and their further sequestration.
In fact, not all red blood cells circulating in the blood stream undergo passage through the splenic sinuses, but only 10% of their total mass. Due to the fact that the fenestra of vascular sinuses have a much lower lumen than the diameter of the standard blood cell of the erythrocyte series, old cells that differ in the rigidity of the envelope are retained in sinusoids. Subsequently, red blood cells undergo metabolic disorders due to low acidity and low glucose concentration in the region of splenic sinuses. Elimination of the delayed in the erythrocyte sinuses occurs with the help of macrophage cells, which are constantly present in the spleen. Thus, intracellular hemolysis is the direct destruction of the blood cells of the erythrocyte series by the macrophages of the reticuloendothelial system.
Depending on the primary localization of the process of erythrocyte destruction, two main forms are distinguished: intracellular and intravascular hemolysis.
Extravascular hemolysis destroys up to 90% of erythrocytes under the condition of normal functioning of the structures of the reticuloendothelial system. The destruction of hemoglobin consists in the primary cleavage of iron and globin molecules and the formation of biliverdin under the influence of hemoxygenase. Later, a chain of enzymatic reactions is launched, the final product of which is the formation of bilirubin and its entry into the total blood flow. At this stage, activation of hepatocytes takes place, the function of which is directed to the absorption of bilirubin from the blood plasma. In a situation where the patient has a significant increase in the concentration of bilirubin in the blood, some of it does not bind to albumin and is filtered in the kidneys.
Adsorption of bilirubin from the plasma occurs in the liver parenchyma by activation of transport system structures, after which it is conjugated to glucuronic acid. This chemical transformation occurs with the participation of a large number of enzymatic catalysts, the activity of which directly depends on the state of hepatocytes. The newborn child has a low enzymatic activity of the liver, and therefore, excessive hemolysis in children is due precisely to the inability of the liver to conjugate bilirubin rather quickly.
Further transformation of conjugated hemoglobin consists in its isolation by hepatocytes together with bile, which also contains other complexes (phospholipids, cholesterol, bile salts). In the lumen of the bile ducts, bilirubin undergoes a chain of changes under the influence of the enzyme dehydrogenase and the formation of urobilinogen, which is absorbed by the structures of the duodenum and subjected to further oxidation in the liver. Part of bilirubin, which is not absorbed in the small intestine, enters the small intestine, where a new form of it, the sterocilibinogen, is formed.
Most of the sterocilinogen is excreted with caloric masses, and the rest is excreted in the urine in the form of urobilin. Thus, intensive hemolysis of erythrocytes can be monitored by the method of determining the concentration of sterolibulin. At the same time, to assess the intensity of hemolysis, an increase in the concentration of urobilinogen should not be considered, which increases not only in the situation when there is increased hemolysis, but also in the morphological and functional damage of the mass of hepatocytes.
The main diagnostic criteria reflecting the process of increased intracellular hemolysis is an increase in the concentration of the conjugated fraction of bilirubin, as well as a sharp increase in the release of stercobilin and urobilin with natural biological fluids. Development of pathological intracellular hemolysis is facilitated by the hereditary inferiority of the erythrocyte membrane in the patient, a violation of hemoglobin production, and an excessive number of blood cells of the erythrocyte series, which occurs with physiological jaundice.
With physiological intravascular hemolysis, the destruction of blood cells of the erythrocyte series occurs directly in the flow of circulating blood, and the constituent of this type of hemolytic reaction does not exceed 10% of the total mass of degrading erythrocytes. A normal intravascular hemolysis reaction is accompanied by the release of hemoglobin and binding of the latter to plasma globulins. The resulting complex enters the structures of the reticuloendothelial system and undergoes further transformations.
Massive intravascular hemolysis is accompanied by a decreased hemoglobin binding capacity of plasma globulins, which is reflected in the form of the release of a large amount of hemoglobin through the structures of the urinary tract. Entering the kidneys, hemoglobin causes in its structures a change in the form of hemosiderin deposition on the surface of the epithelium of the renal tubules, which causes a decrease in tubular reabsorption and the release of free hemoglobin along with the urine.
It should be taken into account that there is no clear correlation between the degree of manifestation of hemoglobinemia and the intensity of release of free hemoglobin in the urine. Thus, the reduced hemoglobin-binding capacity of plasma is accompanied by the development of hemoglobinuria even with a slight increase in the concentration of hemoglobin in the blood. Thus, the main markers of the increased intravascular variant of hemolysis flow are an increase in the concentration of free bilirubin in the urine and in the blood, as well as concomitant hemosiderinuria.
Development of pathological variant of intravascular hemolysis is promoted by various pathological states of toxic, autoimmune, parasitic genesis.
Treatment of hemolysis
In view of the fact that the acute hemolytic crisis belongs to the category of urgent conditions, specialists developed a single algorithm for providing emergency care for this category of patients, including a medicamentous and non-medicamentous component. Kupirovanie signs of a hemolytic crisis in an acute period should be carried out only in a hospital setting of the hematologic profile on the beds of the resuscitation department.
In a situation where hemolysis is accompanied by a critical reduction in hemoglobin, the only effective method of treatment is transfusion of erythrocyte mass in a calculated daily volume of 10 ml per 1 kg of the patient's body weight. In the case of available signs of an arrhythmic crisis, transfusion therapy is recommended to be supplemented with anabolic steroids (Retabolil 25 mg once every 2 weeks).
The presence of signs of acute autoimmune hemolysis in the patient is the basis for the use of glucocorticosteroid drugs. The initial daily dose for Prednisolone is 60 mg, but in some situations the dose may increase to 150 mg. After cupping the crisis, it is advisable to gradually reduce the dosage (no more than 5 mg per day) to the level of 30 mg. A further reduction in dosage involves taking the drug with a smaller 2.5 mg dose every fifth day until complete withdrawal.
In a situation where the therapy with glucocorticosteroid drugs does not have the proper effect in the form of remission periods of 7 months or more, it is recommended that the patient be provided with an operative aid for the removal of the spleen.
Refractory forms of autoimmune hemolysis imply the simultaneous use of glucocorticosteroid drugs and immunosuppressive drugs (Imuran in the calculated daily dose of 1.5 mg per 1 kg of the patient's weight).
The deep stage of the hemolytic crisis should be cured by transfusion of erythrocyte mass after the Coombs test. In order to arrest hemodynamic disorders that often accompany the course of acute hemolysis, intravenous administration of Reogluman is recommended at a calculated dose of 15 ml per 1 kg of the patient's weight.
The presence of signs of urea and creatinine growth in the patient is the basis for hemodialysis. It should be borne in mind that a violation of the technique and changing the composition of the dialysing fluid can in itself provoke the development of an enhanced hemolytic reaction.
In order to prevent the development of renal failure, patients with hemolysis should be prescribed sodium bicarbonate at a dose of 5 g with a simultaneous oral intake of Diacarb in a dose of 0.25 g.
Medicamentous treatment of hemolysis in children of the newborn period is the first replacement of the transfusion of Rh-negative blood. Calculation of the required amount of injected blood is 150 ml / kg of weight. Blood transfusion should be combined with adequate glucocorticosteroid therapy (an intramuscular Cortisone dose of 8 mg in a short course). Signs of damage to the structures of the central nervous system are leveled after applying Glutamic acid in a dose of 0.1 g orally.
To non-medicamentous methods of preventing recurrence of hemolysis in newborns is the rejection of breastfeeding.
? Hemolysis - which doctor should I contact ? If there is or suspected hemolysis, you should immediately seek advice from such doctors as a hematologist or transfusiologist.