Hemolytic anemia is a clinico-hematological symptom complex that occurs as a result of the shortening of the duration of the functioning of red blood cells due to their increased disintegration. This pathology combines a group of diseases of a hereditary and acquired nature, in the pathogenesis of which the hemolysis of erythrocytes predominates without a decrease in hemoglobin in the peripheral blood. According to world statistics, in the structure of morbidity among blood pathologies, hemolytic states account for no less than 5%, of which the hereditary types of hemolytic anemia prevail.
Signs of hemolytic anemia occur only when there is an obvious imbalance between the proliferation of red blood cells and the destruction of erythrocytes in the flow of circulating blood, while the compensatory function of the bone marrow (increased proliferation of reticulocytes) is depleted.
Autoimmune hemolytic anemia
The main provoking factor in the emergence of hemolytic anemia of an autoimmune character 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 a background of any symptomatic disease as a complication (systemic connective tissue diseases, hemoblastosis, chronic aggressive hepatitis, ulcerative colitis , malignant neoplasms) or as an independent nosological unit.
Despite the rapid development of medicine in the field of diagnostic measures of blood diseases, to this day it is not possible to establish a reliable cause of the development of autoimmune hemolytic anemia.
All clinical manifestations of autoimmune hemolytic anemia do not depend on the etiologic factor. Most often, patients experience a slow-progressive course of the disease. The first manifestations of the disease are general weakness, aching joint pain, subfebrile body temperature, abdominal pain. With an objective examination of the patient there is a marked paleness and pastness of the skin, gradually increasing jaundice, an increase in the size of the spleen and liver.
In 50% of cases, patients have 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, numerous complaints of the patient come to the fore in the full absence of changes during an objective examination of the patient. The main complaints that the patient presents are: severe weakness and decreased performance, heart palpitations, a feeling of lack of air, an increase in body temperature to 38-39 degrees Celsius, headache and dizziness , nausea and vomiting unrelated to eating, surrounding aching pain in upper half of the abdomen. External manifestations of hemolysis is only the increasing icterus of the skin in the absence of an increase in the size of the liver and spleen.
Signs of hemolytic anemia of an autoimmune nature in a laboratory blood test are: high reticulocytosis 200-300%, a decrease in the number of red blood cells with a normal color index, a slight leukocytosis, the amount of platelets is not changed or slightly reduced. An absolute indicator of the autoimmune nature of anemia is an increase in ESR to high figures. In some cases, it is possible to identify microspherocytes or fragmented red blood cells. When biochemical blood test is determined by the increase of indirect bilirubin, hypergammaglobulinemia. To determine the presence of antibodies on erythrocytes, a specific Coombs test is performed, which becomes dramatically positive for autoimmune hemolytic anemia.
The prognosis for life and safety of work in autoimmune hemolytic anemia depends on the course, severity and effectiveness of the underlying therapy, which was the cause of hemolysis. As a rule, complete recovery and recovery of work capacity can not be achieved with any method of treatment. Strong remission is observed only after radical splenectomy and a long course of hormone therapy.
Causes of hemolytic anemia
The cause of hemolysis of red blood cells can serve as any somatic disease and in this situation, the acquired hemolytic anemia develops.
When the effect of this or that etiological factor develops a clinic of acute or chronic hemolytic state.
Acute hemolytic anemia often occurs when: massive transfusion is incompatible with the group or the rhesus factor of the blood, the toxic effects of medicinal preparations of certain groups (nitrofurans, sulfonamides, quinidine, antipyretics), prolonged exposure to chemical compounds (benzene, lead), toxins exposure to snake bites , burns to the skin, parasitic diseases.
Chronic course of hemolytic anemia is observed with paroxysmal nocturnal hemoglobinuria, cold hemoglobinuria.
Hemolytic anemia symptoms
Classical symptoms with 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, indicative of the development of anemic condition, directly depends on the rate of erythrocyte destruction and the compensatory response of the bone marrow, as the main blood-forming organ. Signs of anemia develop only in a situation where the life span of red blood cells is reduced to 15 days, instead of 120 days.
With the flow, latent (compensated), chronic (with pronounced anemization), and hemolitic anemia are distinguished. In the course of the disease, a severe general condition of the patient is noted, regardless of the type of hemolysis (intravascular or intracellular).
During the exacerbation, hemolytic anemia manifests itself in the form of severe weakness, decreased efficiency, dizziness, difficulty breathing, increased heart rate, drawing pain in the right and left hypochondrium. A characteristic feature of acute hemolytic anemia is the incidence of skin, mucous membrane of the soft palate and sclera. In an objective examination of the patient, in 70% of cases, an increase in the spleen and protrusion of the liver from beneath the costal arch more than 2 cm.
Due to thickening and stagnation of bile, the formation of concrements in the gallbladder and bile ducts is provoked, therefore patients suffering from hemolytic anemia often make complaints typical of hepatitis, cholecystitis and cholangitis (acute pain in the right hypochondrium, nausea, vomiting, chills, short-term increase in body temperature ).
In the human body, there is a permanent physiological erythrocytic hemolysis in the spleen. During the destruction of hemoglobin, indirect bilirubin is released into the flow of circulating blood, which later undergoes changes in structure and composition in the liver, gallbladder and intestine. The elimination of the formed urobilin and stercobilin occurs together with urine and feces, so that patients often notice darkening of the urine and light feces.
In a situation where there is intravascular destruction of red blood cells, the symptoms of anemic syndrome come to the fore, while jaundice and splenomegaly are very rare. This type of hemolytic anemia is characterized by a crisis course of the disease, which significantly worsens the patient's condition. Characteristic symptoms of the hemolytic crisis are: general weakness, throbbing headache, a feeling of lack of air, increased heart rate, indomitable vomiting, unrelated to food intake, gnawing pains in the upper squares of the abdomen and lumbar region, fever, dark brown urine. In the absence of adequate therapy, a clinic of acute renal failure rapidly develops, which causes death.
Laboratory signs of hemolytic anemia are: normochromicity, hyperregeneration and changes in the shape and size of erythrocytes (crescent, oval, microspherocytes, target). Typical changes in autoimmune hemolytic anemia are leukocytosis with a shift of the leukocyte formula to the left and a sharply increased ESR. With bone marrow puncture, hyperplasia of the red shoot and pronounced erythroblastic reaction are detected.
Hemolytic anemia in children
In childhood, both congenital and acquired forms of hemolytic anemia are observed. All hemolytic anemias have a common clinical symptomatology, but they require an accurate diagnosis indicating the form of anemia, as further tactics of treatment and monitoring of the patient depend on this.
Congenital hemolytic anemia, fortunately, is a rare disease and is no more than 2 cases per 100 000 population, but it should be treated with extreme attention to children suffering from this form of anemia, since the treatment of such patients is extremely difficult.
Hereditary hemolytic anemia of Minkowski-Schoffar is caused by the manifestation of a defective gene, inherited in an autosomal dominant type, causing a change in the shape of red blood cells. The shape changes as a result of the disruption of the cell membrane, and therefore it becomes permeable for the penetration of excess sodium ions, thereby inducing the swelling of the erythrocyte. Excess hemolysis of such altered erythrocytes occurs outside the splenic pulp.
The debut of the disease is observed in early childhood and the first manifestations is the icterity of the mucous membranes and skin. Distinctive features of this form of hemolytic anemia is a combination of pronounced anemic syndrome with developmental anomalies (dolichocephalic shape of the skull, saddle nose, high location of the hard palate).
The main criteria for establishing the diagnosis of hereditary anemia of Minkowski-Shoffar are: normochromic, hyperregeneration of anemia, erythrocyte microspherocytosis, decreased osmotic resistance of erythrocytes, an increase in the index of indirect bilirubin in the blood, an increase in the size of the spleen.
The prognosis for life and health is favorable for this form of anemia, occurs only after the implementation of radical splenectomy.
Another form of hereditary hemolytic anemia occurring in childhood is anemia, caused by a lack of activity of G-6-FDH, which is characterized by an autosomal recessive type of inheritance.
A characteristic feature of this pathology is the occurrence of spontaneous intravascular hemolysis after taking certain groups of drugs (sulfonamides, quinine derivatives, antiplatelet agents, levomycetin, tubazid) or the use of legumes.
Clinical manifestations occur 2-3 days after application of the drug and are manifested in the form of severe weakness, nausea and vomiting, increased heart rate, fever to febrile digits, anuria and acute renal failure. Distinctive features of this form of hereditary hemolytic anemia are hemoglobinuria and hemosiderinuria.
Typical changes in the parameters of peripheral blood are: a decrease in the number of erythrocytes and high reticulocytosis, the presence in the erythrocyte of Heinz bodies with supripital staining, an increase in the osmotic resistance of erythrocytes. In the bone marrow punctate, the hyperplastic red blood of the hematopoiesis is determined.
This type of anemia is characterized by a crisis current, therefore, as a preventive measure, the child must completely eliminate the legumes from the diet, and also prevent the use of drugs from the risk group. Due to the fact that hereditary anemia often occurs with the development of fulminant hemolytic crisis, accompanied by acute renal failure, the prognosis for the life and health of the child is unfavorable in this case.
The most common form of hereditary hemolytic anemia in childhood is thalassemia , in which erythrocyte contains pathologically excessive globin, which promotes accelerated aggregation and destruction of erythrocytes not only in the spleen, but also in the bone marrow.
The first manifestations of thalassemia are observed already in the period of newborns and are manifested by pronounced anemic syndrome, jaundice and splenomegaly combined with developmental anomalies (square skull shape, protruding zygomatic arch, Mongoloid type of face, flattening of nose bridge). In children suffering from thalassemia, there is a lag in not only physical, but also psychomotor development.
Typical laboratory signs of thalassemia in children are: severe anemia (decrease in hemoglobin level less than 30 g / l), hypochromicity (decrease in color index below 0.5), reticulocytosis, target form of erythrocytes when testing a smear, increased osmotic resistance of erythrocytes, high level of indirect bilirubin. Absolute criterion for establishing the diagnosis of "thalassemia" is an elevated level of fetal hemoglobin (more than 30%).
Thalassemia is a constantly progressing pathology, for which the period of remission is not typical, and therefore, the level of mortality in this disease is very high.
Hemolytic anemia treatment
In order to achieve the maximum positive result from the treatment of hemolytic anemia, first of all, every effort should be made to reliably refine the form of the disease, since each treatment regimen must be etiopathogenetically conditioned.
Thus, radical splenectomy is used as a priority method of treatment of hereditary microspherocytic hemolytic anemia. Absolute indications for splenectomy are: the course of the disease with frequent periods of exacerbation, severe degree of anemia and hepatic colic. In most cases, after splenectomy, there is a 100% remission without manifestations of recurrence of the disease, even despite the presence of microspherocytes in the blood. In a situation where hemolysis is accompanied by the appearance of concrements in the gallbladder, it is recommended to combine splenectomy with cholecystectomy.
As a preventive measure, patients are recommended long-term use of cholagogue (Allochol 1 tablet at each meal), spasmolytic (Riabal 1 capsule 2 r./day) drugs, periodic exercise duodenal sounding. In situations where there is a pronounced degree of anemia, it is advisable to use symptomatic replacement transfusion of erythrocyte mass taking into account group affiliation.
In the case of hereditary hemolytic anemia caused by G-6-FDH deficiency, detoxification therapy (200 ml isotonic sodium chloride solution intravenously), as well as preventive measures to prevent DIC syndrome (Heparin 5000 ED subcutaneously 4 r./day), is recommended.
Autoimmune hemolytic anemia responds well to hormone therapy, which is used not only to stop the hemolytic crisis, but also as a long-term use. To determine the optimal dosage of Prednisolone, it is necessary to take into account the general well-being of the patient, as well as the parameters of peripheral blood. An adequate daily dose of Prednisolone in this situation is considered to be 1 mg / kg of weight, but in the absence of effect, an increase in the dose to 2.5 mg / kg is permissible.
In situations where autoimmune hemolytic anemia occurs in severe form, it is advisable to combine detoxification therapy (Neohemodeus 200 ml intravenously) and transfusion of erythrocyte mass, taking into account group affiliation. Radical splenectomy is used only if there is no effect from the use of conservative therapy and should be accompanied by the appointment of cytotoxic drugs (Cyclophosphamide 100 mg 1 r./day, Azathioprine daily dose 200 mg). It should be borne in mind that the absolute contraindication to the use of cytotoxic drugs is child age, since the drugs of this group can cause a mutagenic effect.
Separately it is necessary to stop on such method of treatment, as a transfusion of the thawed or washed up erythrocytes. Transfusion of red blood cells should be justified by the severity of the anemic syndrome and the general condition of the patient and it is necessary to evaluate the patient's response to ongoing blood transfusion. Very often, patients who underwent repeated transfusion of erythrocyte mass, observed posttransfusion reactions, which are the reason for individual blood selection using an indirect Coombs test.
In some cases, hemolytic anemia can be treated with anabolic hormonal medications (Retabolil 25 mg intramuscularly, Nerobol 5 mg 1 dose / day). As symptomatic therapy, it is advisable to use antioxidant drugs (group E vitamins 10 mg intramuscularly), and with concomitant iron deficiency - oral iron-containing drugs (Ferrum-Lek 10 ml 1 r./day).