Autoimmune hemolytic conditions. Can autoimmune hemolytic anemia be cured?

Autoimmune hemolytic anemia (AIHA) is the most common disease among all acquired anemias. The pathogenesis of the disease is associated with a specific disorder in the work of immune processes, in which immune cells (antibodies) begin to recognize erythrocytes (red blood cells) as foreign and fight them. These blood cells are captured and broken down. Their hemolysis occurs in the human liver, spleen, and bone marrow. This is a kind of hypochromic anemia, or rather, its kind.

Why does pathology appear and what are its types?

Like many ailments, autoimmune hemolytic anemia develops against a background of malfunctioning of the immune system. The reasons for this can be damaged parts of DNA or genetic changes. This ailment can also be hereditary. This is due to the ability of DNA to store information in itself and be passed on to the next generation.

The development of the disease can also be associated with the period of bearing a child in the event that an incompatibility of the Rh factors of the blood of a pregnant woman and an embryo occurs.

In practice, there are several types of autoimmune hemolytic anemia:

1. Idiopathic. Characterized by the appearance of autoantibodies unrelated to pathological changes in organism. According to statistics, the number of cases of diseases of the idiopathic form of the disease reaches 50%. Autoantibodies appear due to a violation in the system immune cells, which perceive incorrect information and fight against red blood cells, which leads to the breakdown of the latter.
2. Symptomatic autoimmune anemia appears against the background of existing ailments that, in one way or another, affect the immune system. Most often, an ailment becomes a consequence of such pathological processes as lymphocytic leukemia, a state of acute leukemia, chronic manifestations of arthritis, complex liver diseases.

By the method of studying immunity antibodies human body Autoimmune hemolytic anemias are divided into five subgroups. Each of them has its own characteristics and is manifested by characteristic serological symptoms and clinical course.

The most commonly diagnosed form with incomplete thermal agglutinin, its frequency ranges from 70 to 80% of all anemias of an autoimmune nature.

Such anemias are classified according to clinical picture their course. According to this grading, they can be acute and chronic. The first form is characterized by an abrupt onset. And the chronic course has a more unhurried development of symptoms.

Symptoms

Autoimmune anemia, the symptoms of which differ depending on the course of the disease and its subspecies, can occur with pronounced or less pronounced symptoms:

1. The acute form is characterized by an abrupt onset. The patient complains about sudden weakness, fever. At the same time, his skin acquires a yellowish tint. The patient may have shortness of breath and paroxysmal manifestations of the heartbeat.
2. Chronic autoimmune hemolytic anemia, the symptoms of which often do not appear so dramatically and suddenly, develops slowly. The patient does not notice any changes in his condition, and it is almost impossible to see visually pronounced anemic manifestations. And such a symptom as shortness of breath or palpitations, which is inherent in the acute stage of the disease, is practically not expressed.

The latent course of the chronic form is due to the fact that all processes do not occur so quickly, but the body adapts to changes in the quantitative composition of blood cells, and the state of chronic lack of oxygen becomes normal.

In such patients, during a physical examination, the doctor clearly probes the edges of the enlarged spleen, and sometimes the liver.

Autoimmune anemia, which is associated with allergy to cold, is characterized by the patient's severe rejection of freezing temperatures. In this case, urticaria develops, and the course of the disease itself is characterized by frequent exacerbations. The analyzes show the characteristics of hemoglobinuria, normocytosis, normochromic or hyperchromic anemia. A feature of cold autoimmune anemia is also the adhesion of red blood cells in the analysis, which takes place during warming. The deterioration of the well-being of such patients also occurs during the attachment of viral infections.

Diagnostic features

The disease of hemolytic anemia of an autoimmune nature is diagnosed only if there is a fusion of two symptoms characteristic of the disease:

• symptoms of increased hemolysis;
• detection of antibodies on the surface of red blood cells (erythrocytes).

This analysis is carried out using a direct or indirect Coombs' test. The first study in most cases gives a positive result if the patient has a disease.

And its negative result indicates only the absence of antibodies in the immediate vicinity of red blood cells, but at the same time, it is an indirect test that can indicate the circulation of antibodies in the plasma ( it comes about free cells of the immune system).

A blood test also indicates the development of the disease, and according to its results, this type of anemia can be suspected.

Typical features will be:

• ESR - increased;
• hemoglobin - normal or slightly elevated values;
• a reduced number of red blood cells;
• the presence of reticulocytosis (young erythrocytes with a nucleus).

During biochemistry of biomaterial, bilirubin is increased. This is due to increased destruction of red blood cells.

If the disease is in an acute form, then the number of leukocytes - blood cells in the blood will necessarily increase, which indicates inflammatory processes in organism.

It is important at the time of diagnosis to distinguish hemolytic anemia with an autoimmune onset from ailments that are associated with a lack of enzyme production or microspherocytosis, which is hereditary.

Also, the disease has some similarities with such an ailment as the sickle cell type of hemolytic anemia. Here there is a massive death of erythrocytes, but its development is provoked in most cases by infectious diseases. It is sickle cell HA that can lead to complex complications, especially if this ailment is diagnosed in childhood... Therefore, it is very important to carry out the correct diagnosis and recognize the true cause of the death of red blood cells in the patient's body.

Features of disease therapy

Autoimmune hemolytic anemia, the treatment of which should take place under the strict supervision of a hematologist, in most cases is eliminated by using hormonal drugs from the group of corticosteroids. This is the most commonly used method today. These drugs focus on reducing the body's production of antibodies, which leads to the normalization of the immune response.

The dosage of corticosteroids is selected in accordance with the condition of the patient, and the following basic rules are used for treatment:

• the acute phase is treated with Prednisolone (from 60 to 80 mg per day), the dose can also be increased to 100 mg or more, it is determined strictly by the doctor from an approximate calculation: up to 2 mg / 1 kg of the patient's weight;
• other hormonal drugs from the corticosteroid group can also be used in treatment;
• discontinuation of the drug after stabilization of the patient's condition is not carried out abruptly, but through a gradual decrease in dosage.

Therapy of autoimmune hemolytic anemia is a very difficult and long-term work, after stabilization of the main indicators, it is necessary to keep the patient on maintenance treatment for another two to three months.

Usually for this period, the daily dose of the hormone is no more than 10 mg. Treatment is considered complete when a negative Coombs test is obtained.

In the process of treatment, the following medications are also used:

• Heparin is a direct anticoagulant that has a short effect over 4 to 6 hours. It is used to relieve DIC syndrome, which often develops in the human body as the number of red blood cells in the blood decreases. The drug is injected subcutaneously, every six hours under constant monitoring of blood counts (coagulogram).
• Nadroparin is a drug that is similar in its actions on the human body to Heparin. But its main characteristic is a longer lasting effect, which ranges from 24 to 48 hours. Prescribe a subcutaneous injection of 0.3 ml / day.

• Folic acid is a group of vitamins. She actively participates in the processes of the body, including the processes of formation of erythrocytes. It is often prescribed to activate the internal forces of the body. The initial dose is from 1 mg. If its reception gives a positive effect, then the dosage can be gradually increased to 5 mg.
• Pentoxifylline is considered an additional agent that prevents the development of blood clots and the onset of DIC. In addition to this action, the drug improves blood circulation in the tissues of the patient's systems and organs. The required therapy with this drug is at least three months.
• B12 is a vitamin that takes an active part in the final formation of red blood cells. If the patient has a lack of this substance in the body, then the red blood cells will be larger, and their elastic properties are reduced, which contributes to their faster death.
• Ranitidine - is antihistamine... Its main action is to reduce the functionality of the stomach in the production of hydrochloric acid. Why is it important in the treatment of hemolytic autoimmune anemia? These measures are necessary because they smooth out side effects drugs necessary for therapy (Prednisolone). The recommended dose is 150 mg twice a day.

There are often cases when the patient's body resists the action of the course hormone therapy... In this case, the disease begins to progress with frequent acute clinical manifestations. If it is not possible to receive a positive answer, then it is often appointed surgical intervention, in which the spleen is resected. Such surgery called splenectomy. Due to this removal, it is possible to achieve a decrease in the content of antibodies in the blood, which destroy red blood cells.

The operation is performed under general anesthesia. Depending on the place of access to the organ, the patient is placed on his back or on his side. Through the incision, the blood vessels are ligated and the organ removed. After that, the doctor makes an audit abdominal cavity for the presence of additional spleens in the patient. This anomaly is extremely rare, but it can still be observed, and the surgeon must make sure that it is absent. If the check is not carried out, and the patient will be with such an anomaly, the long-awaited remission of the underlying disease will not be observed, since the destruction of red blood cells will be produced by the residual accessory spleens.

For some patients with signs of autoimmune anemia, a course of immunosuppressants is prescribed.

These drugs include:

• Cyclosporin A - administered intravenously using a dropper, is actively prescribed after splenectomy;
• Azathioprine and Cyclophosphamide - drugs are prescribed at 200 mg per day, the course of therapy is from two to three weeks;
• Vincristine.

Severe crises need to be stopped by infusion therapy (saline solutions), transfusion of a donor mass of erythrocytes.

In severe advanced forms of this autoimmune blood disease, plasma transfusion from a donor, plasmapheresis, or hemodialysis are also used.

Any blood transfusion should be carried out only according to vital signs (soporous complication). At the same time, it is important to select donor transfusions with mandatory testing for Coombs' test.

Forecast and prevention

It should be noted that it is almost impossible to predict the development of such an autoimmune blood disease, so there is no need to talk about any targeted preventive measures. The basis here remains healthy image life and proper nutrition person.

Nevertheless, medical science identifies a number of preventive measures aimed at preventing autoimmune anemia.

They are classified as primary and secondary:

1. The main effect of primary prevention is to ensure the prevention of an autoimmune pathological process in the body.
2. And the secondary is focused on alleviating the condition of those patients in whom the disease has arisen and progressed.

In the case of idiopathic autoimmune anemia, there are no primary preventive measures, since the patient does not have the reasons for its occurrence. Symptomatic secondary anemias are characterized by a number of preventive measures. Their main function is to prevent the development of diseases that are potentially dangerous and can develop autoimmune processes in the body.

TO preventive measures can be attributed to the avoidance of the influence of natural factors that contribute to the development of anemia. These include avoiding low ambient temperatures (for cold anemias) and, conversely, high temperatures (for a disease with warm antibodies).

After the therapy, which is accompanied by complete or partial remission of the general ailment, the patient is recommended to undergo control laboratory tests for at least two years to prevent the recurrence of autoimmune anemia.

The frequency of such laboratory tests is determined by the doctor, they are recommended to be carried out once every three months.

If the results indicate an exacerbation of the pathological process, the doctor decides on re-holding all the necessary diagnostic methods, and according to their indicators, the need for further therapy is determined. Such control helps to identify the onset of relapse in time and stop it in the early stages.

Unfortunately, modern medicine does not always give a positive prognosis. Whether or not an autoimmune disease can be cured depends largely on its form. But it should be noted that for last years therapeutic methods against the disease are bearing positive results, and many doctors and patients are achieving positive results.

Statistics also speak of such indicators:

• if the therapy of primary idiopathic anemia of an autoimmune nature is carried out with hormonal drugs, then recovery occurs in 10% of cases;
• with splenectomy, this percentage of effectiveness increases to 80%;
• more high performance can be achieved by immunosuppressive therapy (up to 95%).

If we talk about secondary symptomatic anemias, then the effectiveness in this case directly depends on how the disease that caused such pathological processes is treated.

The term "hemolytic anemia" means a group of hereditary or acquired diseases, which are characterized by increased intravascular or intracellular destruction of red blood cells. Hemolytic anemia can be immune, idiopathic, and autoimmune. But most often it is autoimmune hemolytic anemia (AGA) that occurs - 1 case per 75 thousand population.

All autoimmune hemolytic anemias include diseases characterized by the formation of antibodies to erythrocyte self-antigens.

Causes of autoimmune hemolytic anemias

Like any autoimmune disease, autoimmune anemia is the result of a malfunctioning immune system. The cause of such a failure can be gene mutation and damage to the DNA chain under the influence of various harmful factors.

As you know, DNA is a molecule that provides storage and transmission of information, and therefore anemia can be inherited. That is why the prevention and successful treatment of autoimmune hemolytic anemia primarily consists in optimizing the functioning of the immune system.

Classification of autoimmune hemolytic anemias

Depending on the cause of the development, autoimmune hemolytic anemia can be symptomatic and idiopathic. In the first case, it develops as a complication of some other disease. In the second case, there is no obvious reason for the development of the disease.

Depending on the antibodies that attack the red blood cells, this disease is classified into 4 subspecies. So, there is autoimmune hemolytic anemia:

• With incomplete thermal agglutinins: when red blood cells attack immunoglobulins A and G - protein molecules. The disease usually develops rapidly and acutely. The main symptoms: fever, general weakness, shortness of breath, back pain. The destruction of blood occurs mainly in the spleen;
• With thermal hemolysins: destruction of red blood cells occurs under the action of hemolysins (cells that damage blood cells) in blood vessels... Against the background of this type of disease, blood clotting increases, as a result of which microthrombi form in the patient, acute renal failure often develops;
• With complete cold antibodies: poor cold tolerance - main feature this form of the disease. Also, patients complain of rapid fatigue, weakness, shortness of breath. In summer, the disease may not make itself felt at all, but worsens in the cold season. Elderly people are most often affected;
• With biphasic hemolysin antibodies - very rare view anemia, which is characterized by the fixation of biphasic hemolysin on the surface of the erythrocyte. This process possible only in cold conditions, therefore hemolysis is always preceded by hypothermia.

The chronic form of autoimmune hemolytic anemia is usually almost asymptomatic, periodically exacerbating. Against the background of remission on palpation, an increase in the spleen and liver is determined, sometimes jaundice occurs.

A detailed blood test in patients with AGA shows an increase in ESR, normal level platelets, increased or normal hemoglobin. With an exacerbation of chronic anemia or with an acute illness, the number of leukocytes increases (in the stage of remission, this indicator is normal).

It is rather difficult to diagnose autoimmune hemolytic anemia; for this, a number of specific diagnostic studies are carried out.

Treatment of autoimmune hemolytic anemia

Treatment of autoimmune hemolytic anemia is carried out with glucocorticosteroid drugs, most often prednisolone. It is prescribed in a daily dose of 40-60 mg for three weeks. If this course does not lead to remission, the dosage of the medication is doubled. Signs of remission include an increase in the content of reticulocytes in the blood, after which either the hematocrit level also rises, or at least a tendency towards positive dynamics is outlined. Resistance to this treatment regimen is considered a poor prognostic sign.

Since a direct antiglobulin test can remain positive for a long period, even despite clear signs of improvement, patients are advised to carry out an indirect antiglobulin test - it is sensitive to the effectiveness of therapy.

In the stage of remission of the disease, as well as in order to prevent relapses, the daily dose of corticosteroids is gradually reduced by 2.5-5 mg per day and until complete cancellation.

In the absence of the desired effect of therapy with drugs of this group, as well as with increased resistance to hormonal drugs, patients whose course of the disease is practically not amenable to drug correction and is accompanied by frequent relapses, recommend splenectomy - surgery to remove the spleen. Such a radical measure can significantly improve the quality of their lives.

If there is no result from the use of corticosteroids, patients can also be prescribed immunosuppressive drugs, for example, 6-mercantopurine (at the rate of 2 mg per 1 kg of body weight per day) or azathioprine (1.5-3.0 mg per kg / day).

In severe hemolytic crises that threaten human life, it is shown infusion therapy: hemodesis, individually selected erythrocyte mass. In some cases, blood plasma, frozen or washed erythrocytes are transfused. Sometimes, with autoimmune hemolytic anemia, they resort to the method of plasmapheresis and hemodialysis.

It should be noted that corticosteroid drugs show little therapeutic efficacy in the treatment of hemolytic anemias caused by cold antibodies. For this reason, the prevention of hypothermia of the body is the basis for the prevention of this form of the disease. In severe cases of the disease, immunosuppressive drugs are prescribed (chlorbutin, cyclophosphamide, etc.).

Treatment of autoimmune hemolytic anemia in chronic stage carry out prednisolone in a daily dosage of 20-25 mg. As the blood counts improve, the dose is gradually reduced to a maintenance dose of 5-10 mg / day.

Despite the rather high level development of modern medicine, treatment of all types of hemolytic anemias is a complex process, and the diagnosis, unfortunately, is often unfavorable.

Various pathological processes that take place in the immune system can inevitably lead to serious disorders. An autoimmune disorder is characterized by the fact that the body begins to consider its own cells "enemy" and begins to fight with them. Autoimmune hemolytic anemia belongs to a group of rare diseases in which the formation of antibodies to its own erythrocytes is observed. The consequences of this phenomenon are quite serious, since violations of the circulatory system affect the work of the whole organism.

All autoimmune pathological disorders appear as a result of malfunctions of the immune system. Also, a hereditary factor is not excluded, which predisposes to the appearance immune diseases... In newborns, incompatibility with the mother's Rh is diagnosed. Another reason for the appearance of this disorder can be damage to the DNA chain or due to gene mutations.

Acquired autoimmune hemolytic anemias are classified according to the factor that triggered the progression of the disease. In the case when it is impossible to associate the formation of a provoking factor due to which rejection of erythrocytes appears, it is customary to diagnose idiopathic anemia. Unspecified anemia accounts for almost half of all cases of the disease.

Symptoms of autoimmune anemia

The manifestations of the disease directly depend on the form, of which there are only two - acute and chronic. The acute form is characterized by the following manifestations:

1. The appearance of rapidly progressive painful sensations.
2. Shortness of breath even with light exertion.
3. Painful discomfort in the region of the heart.
4. There is an increase in body temperature, vomiting.
5. The appearance of yellowness of the skin.

The chronic form outwardly manifests itself in a relatively satisfied state of the patient, even if the disease has long been neglected. Often, yellowness of the skin appears, an enlargement of the spleen is diagnosed with ultrasound. Periods of exacerbation alternate with a calm course of the disease. Autoimmune hemolytic anemia code for the ICD 10 directory stands for D59.

With cold autoimmune anemic disease, poor tolerance to low temperatures may occur. In the cold, patients show characteristic signs of the disorder: urticaria and Raynaud's syndrome. Raynaud's syndrome is characterized by numbness and pain in the limbs of the hands, the appearance of a bluish tinge of the skin, the tip of the nose, tongue and ears also suffer. At infectious diseases possible exacerbation of anemic syndrome.

Autoimmune hemolytic anemia in children

Young children are often diagnosed with a rather rare form of autoimmune hemolytic anemia - anemia with biphasic hemolysin. Also has a second name - cold anemia. The characteristic signs of the disorder are the following manifestations: chills, fever, abdominal pain, nausea and bouts of vomiting, with hypothermia, a black tint of urine appears. During an exacerbation, ultrasound reveals an increase in the size of the spleen, an icteric tint of the skin appears.

Diagnostics

Clinical and hematological signs provide a basis for the diagnosis of autoimmune hemolytic anemia. Also, for diagnosis, a Coombs test is carried out, which reliably reflects the patient's condition. According to the blood picture, the presence of microspherocytes, normoblasts, normochromic anemia is determined. ESR level often significantly increased, and also increased the level of bilirubin in the blood.

Treatment of autoimmune hemolytic anemia

For the treatment of autoimmune anemia, you need to see a hematologist. Autoimmune anemia often occurs with pronounced clinical manifestations, and therefore the specialist prescribes, first of all, medications with a potent effect. Such drugs are aimed at suppressing the immune system.

All therapeutic measures are carried out for almost three months. A negative Coombs test is considered a productive result. Only after that, the therapeutic therapy is stopped. In some cases, autoimmune anemic pathology does not respond to treatment. Then only surgical intervention is prescribed - removal of the spleen.

In the acute course of the disease, a blood transfusion may be required. Also, prednisolone is prescribed for cold or chronic anemia. The disease is difficult to treat. Despite all modern therapeutic therapies, the prognosis for autoimmune anemia is often poor.

Prophylaxis

It is not possible to prevent or anticipate the appearance of such a disease, and therefore there are no practical preventive methods. It should be added that the most effective and effective way a warning against any disease advocates a healthy lifestyle.

Autoimmune hemolytic anemia is understood as a form of anemia in which antibodies are produced against their own unchanged antigen. In these cases, the immune system perceives its own antigen as foreign and produces antibodies against it.

Depending on what is the object of destruction - erythrocytes peripheral blood or erntrokaryocytes of the bone marrow, there are two groups of autoimmune hemolytic anemias - with antibodies against antigens of erythrocytes of peripheral blood and with antibodies against antigens of erythrokaryocytes.

All autoimmune hemolytic anemias, regardless of the cellular orientation of antibodies, can be divided into idiopathic and symptomatic.

Symptomatic anemias include anemias in which antibodies are produced in response to some other disease - hemoblastosis (especially lymphoproliferative diseases such as chronic lymphocytic leukemia, Waldenstrom's disease, multiple myeloma, lymphosarcoma), systemic lupus erythematosus, ulcerative colitis, rheumatoid arthritis active hepatitis, malignant tumor different localization, immunodeficiency state.

In cases where autoimmune hemolytic anemias occur for no apparent reason, they should be classified as idiopathic. So, AIHA, arising after influenza, tonsillitis and other acute infections, during pregnancy or after childbirth, are symptomatic, since these factors are not etiological, but provoking clinical manifestations of a latent disease.

Autoimmune hemolytic anemias with antibodies to antigens of erythrocytes of peripheral blood are divided into four types based on the serological characteristics of antibodies:

1. with incomplete thermal agglutinins;
2. with thermal hemolysins;
3. with full cold agglutinins;
4. with biphasic cold hemolysins.

AIHA with involuntary thermal agglutinins is most often detected. This form of anemia occurs at any age. AIHA with complete cold agglutinins is observed mainly in the elderly. AIHA with biphasic hemolysins is the rarest form; occurs mainly in young children. With symptomatic forms of the disease, the age of patients can be different.

Autoimmune hemolytic anemia with antibodies against peripheral blood erythrocyte antigens

Anemia Associated with Incomplete Thermal Agglutinins

Clinical manifestations

Clinical manifestations do not depend on whether the patient has an idiopathic or symptomatic form of anemia. The onset of the disease can be different. Sometimes it is acute: against the background of complete well-being, a sharp weakness suddenly appears, sometimes pain in the lower back, in the region of the heart, shortness of breath, palpitations, fever is often noted. Jaundice develops very quickly, which most often serves as the basis for a misdiagnosis of infectious hepatitis.

In other cases, a more gradual disease is observed. There are precursors of the disease - arthralgia, abdominal pain, low-grade fever.

Often, the disease develops gradually. The patients feel well. Shortness of breath, palpitations are absent in them, despite even severe anemization, which is associated with the patient's gradual adaptation to anemic hypoxia.

Laboratory indicators

In acute hemolytic crises, there is a decrease hemoglobin to extremely small numbers (less than 3.1 mmol / l, or 50 g / l). However, in most cases, the hemoglobin content does not decrease so sharply (3.72-4.34 mmol / l, or 60-70 g / l). In a number of patients with a chronic course of autoimmune hemolytic anemia, a slight decrease in hemoglobin is observed (up to 5.59 mmol / l, or 90 g / l). Anemia is most often normochromic or moderately hyperchromic.

The content of reticulocytes in the majority of patients it is increased, sometimes to a large extent (up to 87%). In the symptomatic form of the disease, the reticulocyte count is lower than in the idiopathic one. With an exacerbation of the disease, the content of reticulocytes sometimes decreases to 0.1-0.3%. Macrocytosis may occur, but microspherocytosis is most commonly found. The number of microspherocytes is the same as in hereditary microspherocytosis. This symptom is not pathognomonic for this disease. In severe cases of the disease, schizocytes are found.

In the bone marrow, in most cases, the red sprout is hyperplastic, however, a decrease in the number of erythrokaryocytes is possible. Probably, these crises are associated with a very large number of antibodies, as a result of which not only the erythrocytes of the peripheral blood are destroyed, but also the erythrokaryocytes. However, it cannot be ruled out that the cause of crises, as well as with microspherocytosis, and with sickle cell anemia, is infection with parvovirus.

Leukocyte count depends on the disease that underlies AIHA. In the idiopathic form of AIHA, there are significant fluctuations in the number of leukocytes: acute forms diseases - up to 50-70 G in 1 liter with a shift to the left to promyelocytes; in chronic forms - a slight increase or a normal amount. Severe leukopenia is sometimes observed.

Platelet count in most patients, normal or slightly reduced. There is, however, a category of patients who have a combination of autoimmune hemolytic anemia with severe autoimmune thrombocytopenia or simultaneous autoimmune damage to all three hematopoietic germs. In some cases, autoimmune hemolytic anemia begins simultaneously with autoimmune thrombocytopenia, in others, thrombocytopenia joins anemia only after several months or years. In some patients, at the onset of the disease, thrombocytopenia is detected and anemia develops only after a certain time. In this case, thrombocytopenia may no longer be observed. Therefore, there is no serious reason for the isolation of the disease or Fisher-Evans syndrome, characterized, as is commonly believed, a combination of autoimmune hemolytic anemia and thrombocytopenia.

Osmotic resistance of erythrocytes in AIHA with thermal agglutinins, it is reduced in most cases. There was a parallelism between the degree of microspherocytosis and changes in osmotic resistance. The change in osmotic resistance is especially pronounced after daily incubation of erythrocytes.

Acid resistance of erythrocytes increases, as a rule, parallel to the degree of intensity of hemolysis and the degree of hyperreticulocytosis. The maximum shifts towards resistant cells until the 6th, 7th or 8th minute of hemolysis, the height of the curve remains normal. The left branch of the curve becomes flatter than normal. The total time of hemolysis remains normal or slightly increases.

Bilirubin content in autoimmune hemolytic anemia most often it is increased to 25-45 µmol / l, in some patients - up to 60 µmol / l. In patients with the idiopathic form of AIHA, an increase in the level of bilirubin is observed more often than in the symptomatic form. The increase in the bilirubin content occurs mainly due to the indirect fraction not associated with glucuronic acid. It should be noted that normal bilirubin levels do not exclude the diagnosis of autoimmune hemolytic anemia. An increase in the content of direct, or associated with glucuronic acid, bilirubin may indicate concomitant hepatitis or obstruction.

In urine, the content of urobilin is sometimes increased, but this increase is unstable and is not a sign of hemolytic anemia. In the feces of patients, as a rule, a significant amount of stercobilin is found.

Plasma hemoglobin content may increase due to the presence of small intravascular hemolysis in these patients, but most often it is normal. Sometimes, with autoimmune hemolytic anemia with incomplete thermal agglutinins, severe hemosiderinuria is observed, rarely hemoglobinuria. Changes in the composition of protein fractions, increased ESR are often detected.

In a number of patients, the content of globulins is increased, most often due to immunoglobulins. In some cases, with autoimmune hemolytic anemia with incomplete thermal agglutinins, electrophoresis reveals a homogeneous fraction - the M-gradient. Sometimes with AIHA there is a positive Wasserman reaction.

In some patients, immune hemolytic anemias, having begun acutely, can give, with adequate therapy, a rapid remission, and after a while a new exacerbation may occur. In some patients, autoimmune hemolytic anemia after an acute onset turns into a typical chronic form... In rare cases, the disease is extremely unfavorable and, despite intensive therapy, can be fatal.

Thermal hemolysin anemia

Clinical manifestations

This form of autoimmune hemolytic anemia can begin as acutely as the agglutinin form, but more often it is characterized by a calmer, milder onset. The hemoglobin content decreases to 2.48-3.72 mmol / l (40-60 g / l). There may be slight yellowness of the sclera and skin, but with this form of anemia it is less pronounced than with agglutinin forms of anemia. A slight increase in the spleen and liver is observed in almost half of patients.

A characteristic feature of the hemolysin form of autoimmune hemolytic anemia is the discharge of black urine. During this period, a large amount of protein is found in it, a positive benzidine test is observed (with urine!). Hemoglobinuria is observed relatively rarely and not in all patients, however, in a number of patients, hemosiderinuria is constantly detected. Bilirubin levels are either normal or slightly elevated.

Sometimes the hemolysin form of the disease is complicated by peripheral vein thrombosis. Attacks of abdominal pain associated with thrombosis of small mesenteric vessels may occur.

Laboratory indicators

The blood picture is basically the same as in agglutinin forms of autoimmune hemolytic anemia. A large number of microspherocytes are often found. The number of leukocytes in most patients is increased, in many cases there is a shift in the leukogram to myelocytes. The platelet count is normal.

Differential diagnosis of the hemolysin form of AIHA performed primarily with paroxysmal nocturnal hemoglobinuria (Markiafava-Micheli disease).

Anemia associated with total cold agglutinins

Clinical manifestations

This form of AIHA is characterized by a gradual slow onset. Patients complain of weakness, malaise, decreased performance, cold intolerance. In most patients, after exposure to cold, blue discoloration and then whitening of fingers, toes, ears, and the tip of the nose are noted. There is a sharp pain in the limbs. After prolonged exposure to cold, gangrene of the fingers or toes may develop. However, Raynaud's syndrome is not an obligatory sign of the disease; in some patients, urticaria appears after cooling. The liver and spleen may enlarge.

Laboratory indicators

The hemoglobin level in most patients ranges from 4.96-6.21 mmol / l (80-100 g / l), but it can be lower. The content of leukocytes and platelets usually does not decrease.

Characteristic feature of the cold form of autoimmune hemolytic anemia- autoagglutination of erythrocytes, which is observed immediately during blood sampling. This often interferes with the determination of the number of erythrocytes and ESR. Autoagglutination in the smear is often observed. If blood is stored at room temperature (and even more so in a refrigerator), it agglutinates in a test tube. This agglutination is reversible and disappears completely when heated. The bilirubin content is normal or slightly elevated. When studying protein fractions of blood in a number of patients, a separate protein fraction (M-gradient) is found, which is cold antibodies.

In the urine of some patients, protein is found due to free hemoglobin. However, hemoglobinuria is not a common symptom of the disease.

The combination of moderate anemia with signs of increased hemolysis, a sharp increase in ESR, Raynaud's syndrome, changes in blood protein fractions, as well as the inability to determine the blood group and counting erythrocytes should serve as a basis for suspicion of cold hemagglutinin disease and the study of complete cold agglutinins.

The course of the disease is chronic... Clinical manifestations are more pronounced in winter and almost completely absent in summer. In most patients, crises are not observed. Recovering from the idiopathic form practically does not occur, but the disease is extremely rarely fatal.

Sometimes the cold form of immune hemolytic anemia is observed as an episode during the period viral infection(influenza, infectious monoculeosis) or immediately with a decrease in body temperature after an infection. In these cases, clinical signs of the disease may also appear (Raynaud's syndrome, an enlarged spleen, a decrease in hemoglobin levels, a sharp increased ESR, the impossibility of determining the blood group), however, they completely disappear after 1-2 months. This is evidence in favor of a heteroimmune rather than an autoimmune form of anemia.

Anemia associated with biphasic cold hemolysins

Anemia associated with biphasic cold hemolysins (paroxysmal cold hemoglobinuria) is the rarest form of autoimmune hemolytic anemia. It is characterized by attacks of chills, fever, abdominal pain, nausea, vomiting and the appearance of black urine a few hours after hypothermia. Sometimes, as well as with cold agglutinin disease, Raynaud's syndrome is expressed. Soon after cooling, the precursors of the disease may appear: back pain and lower limbs, headache, malaise, and then chills appear and at various intervals (from several minutes to several hours) there is a discharge of dark (almost black) urine. Body temperature lasts for several hours. Black urine can be shed for 1 to 2 days. During a crisis, an increase in the size of the spleen is sometimes noted, and yellowness appears.

Serological diagnosis of autoimmune hemolytic anemias

Diagnosis of AIHA with incomplete thermal agglutinins

The diagnosis of autoimmune hemolytic anemias is confirmed by a positive direct test (reaction) of Coombs, which usually allows detecting incomplete antibodies fixed on the surface of erythrocytes.

Previously, it was assumed that incomplete antibodies have the same valence and therefore cannot combine two red blood cells. It is now known that incomplete thermal agglutinins fixed on erythrocytes have two valences. The absence of agglutination of erythrocytes in a saline medium is explained by the existence of an ion cloud around the erythrocyte and the so-called 2-potential. The repulsion of negatively charged erythrocytes counteracts their slight attraction caused by incomplete antibodies. Therefore, in most cases, incomplete warm antibodies do not lead to the phenomenon of autoagglutination. Sometimes in severe forms of anemia in patients with warm antibodies, the phenomenon of autoagglutination is observed, which can lead to an error in determining the blood group.

The addition of a protein (albumin, gelatin) to erythrocytes leads to dispersion of the ion cloud and agglutination of erythrocytes, on which antibodies are fixed. This is the basis of the method for determining Rh-affiliation. Sometimes the addition of a gelatin solution leads to agglutination of red blood cells, on which autoimmune antibodies are fixed. However, the use of gelatin for the detection of antibodies is not recommended, since only a small proportion of patients with autoimmune hemolytic anemia can be detected. Nevertheless, this phenomenon should be taken into account, since underestimation of it often leads to the diagnosis of a false-positive Rh-affiliation.

The main method for detecting incomplete antibodies fixed on erythrocytes is direct antiglobulin Coombs test... The antiserum obtained by immunizing rabbits with human serum globulin does not cause agglutination of washed normal erythrocytes. The attachment of antiglobulin serum to incomplete antibodies, immunoglobulins fixed on erythrocytes, leads to an increase in the protein sitting on erythrocytes and to agglutination.

A positive direct Coombs' test is observed in most cases of autoimmune hemolytic anemia. However, a negative Coombs test does not exclude the diagnosis of autoimmune hemolytic anemia. It can be observed during the period of the greatest severity of the disease due to the fact that during this period all erythrocytes are destroyed, on which a sufficiently large number of antibodies are fixed. Several patients have a negative Coombs' test during the period of a sharp exacerbation of hemolysis and sharply positive - against the background of massive steroid therapy. A negative Coombs' test may be due to an insufficient amount of antibodies with a mild chronic course diseases.

The sensitivity of the Coombs test can be increased by using aggregate hemagglutination method... For research using this method, test erythrocytes coated with proteins of immune serum aggregated with glutar aldehyde are used. This allows the multiplication effect to be realized: the probability of meeting through the antibody of any two studied erythrocytes increases, which is explained by the huge mass of the test erythrocyte, loaded with a large number of antibodies, in comparison with a single molecule of specific antiglobulin. Aggregation of immune serum proteins with glutaraldehyde allows such aggregates to be planted on the active centers of antibodies at a considerable distance from the surface of erythrocytes, which increases the availability of the active center of antibodies for determinants of immunoglobulins located on the surface of the patient's erythrocyte.

The first stage of the aggregate hemagglutination method is an almost common antiglobulin direct Coombs reaction with rabbit antiserum against human gamma globulin. In the case of a negative sample, erythrocytes are washed from unbound antibodies and then test erythrocytes loaded with aggregated antiserum obtained from another animal (for example, a donkey or ram) immunized with rabbit gamma globulin are added to them.

With the help of a direct Coombs' test, antibodies in autoimmune hemolytic anemia are detected in 65% of patients, in the rest they can be detected only by aggregate hemagglutination.

Both false positive and false negative Coombs' tests can be due to poor quality of the antiserum. This also applies to the aggregate hemagglutination method. Insufficient sorption of heteroantibodies leads to false positive results, and a low titer of antibodies gives a false negative Coombs' test. This study requires the presence of donor erythrocytes for negative control and checking at least once every 3 weeks for the quality of the antiserum for the positive control (donor Rh-positive erythrocytes sensitized with a small amount of anti-Rh antibodies).

Regardless of the method for detecting antibodies in most patients, they belonged to the IgG class, and only in some patients, using the aggregate hemagglutination method, IgA was detected on the surface of erythrocytes.

Indirect Coombs test in the case of autoimmune hemolytic anemia, it has no diagnostic value.

When carrying out this reaction, the donor's erythrocytes are incubated with the patient's serum, washed, and then, as with a direct sample, it is determined whether there are incomplete warm antibodies on the surface of the donor erythrocytes. Antibodies in the patient's serum can be either auto- or isoantibodies. It is possible to talk about autoantibodies only if they are directed against the same antigen as the antibodies found on the surface of the patient's erythrocytes. The indirect Coombs test is used only for the individual selection of erythrocytes.

Diagnostics of AIHA with thermal hemolysins

Diagnosis of AIHA with thermal hemolysins is based on their determination in the blood serum of patients. Direct Coombs test often turns out to be negative. The patient's blood serum in a weakly acidic environment causes hemolysis of the donor's erythrocytes in the presence of complement.

Sucrose test, which is considered characteristic of paroxysmal nocturnal hemoglobinuria, may be positive in the hemolysin form of autoimmune hemolytic anemia. This test is based on the destruction of red blood cells by complement. In paroxysmal nocturnal hemoglobinuria, sucrose and complement destroy erythrocytes with a pathologically altered membrane by producing defective cells. In the hemolysin form of autoimmune hemolytic anemia, the destruction of cells occurs due to antibodies fixed on the surface of erythrocytes. The sugar sample can be supplied in two additional versions. In the first, the patient's blood serum is mixed with the donor's erythrocytes and the presence of hemolysis of the donor's erythrocytes by the patient's blood serum is investigated in the presence of sucrose (crossover); in the second variant, the patient's blood serum is incubated with his own erythrocytes.

With paroxysmal nocturnal hemoglobinuria, the direct, main, variant of the test is positive, the cross variant is negative and the third variant is positive, but the hemolysis is weaker than in the first variant. With the hemolysin form of autoimmune hemolytic anemia, hemolysis is most pronounced in the third variant, since the patient's blood serum contains antibodies that are best fixed on the surface of his own erythrocytes. To a lesser extent, hemolysis is noted in the first, direct, variant and sometimes in the cross. Often gives positive results aggregate hemagglutination method.

Diagnosis of AIHA with complete cold agglutinins

Diagnosis of AIHA with complete cold agglutinins is based on the determination of their titer in blood serum. For this, the serum of patients, taken in the heat, is titrated in a saline medium, donor erythrocytes are added to it, and the mixture is placed in different temperature conditions. Normally, there are cold antibodies in the blood serum, which can cause agglutination of donor erythrocytes in a titer of 1: 4 at a temperature of 4 ° C. In the presence of pathological cold antibodies in the blood serum, their titer is very high.

Agglutination occurs when the patient's blood serum is diluted many thousands of times. In milder forms of the disease, agglutination in a large titer is observed only at low ambient temperatures, and at a temperature of 20 ° C, and even more so 37 ° C, it does not occur. In more severe forms of the disease, agglutination can also occur at a temperature of 20 ° C. To enhance the sensitivity of the reaction, it is advisable to treat the donor's erythrocytes with papain.

Cold antibodies are inherently IgM. With electrophoresis, in most cases, an M-gradient is found, as in Waldenstrom's disease. There are several descriptions of autoimmune hemolytic anemia with cold antibodies belonging to the IgA class.

Diagnosis of AIHA with biphasic hemolysins

Biphasic hemolysins are characteristic of paroxysmal cold hemoglobinuria. Belong to the IgG class.

Their peculiarity is that in the first phase of the study, when the blood serum of a patient with donor's or patient's erythrocytes is placed in a refrigerator, hemolysins are fixed on the surface of the erythrocytes. Then the erythrocytes are placed in a thermostat (second phase), where their hemolysis occurs. Sometimes with paroxysmal cold hemoglobinuria, a positive direct Coombs' test is observed due to the detection of both 1 IgG and complement on the surface of erythrocytes.

For the sera of different patients, in the first phase of the reaction, a different degree of cooling is required - from 0 ° to 25 ° C. Those forms of the disease in which a lower degree of cooling is required in the first phase are more difficult. The second phase of the reaction proceeds best at 32 ° C in a neutral environment.

Antibody specificity

At different forms AIHA antibodies are directed against various antigens. So, in autoimmune hemolytic anemia with incomplete warm agglutinins, antibodies are directed in most cases against an antigen belonging to the Rh system (Rh null). However, it is not a common antigen of the Rh system and is found in almost all people, regardless of their Rh origin. This antigen is associated with a section of the erythrocyte membrane on which the Rh antigens are attached.

In autoimmune hemolytic anemia with complete cold agglutinins, antibodies against system Ii antigens are found in most cases. Antigen I is found in adults and in very small amounts in newborns, antigen i is found in newborns and in very small amounts in adults.

In paroxysmal cold hemoglobinuria, antibodies are directed against the p.

The study of the specificity of antibodies often helps to make the correct diagnosis, recommend treatment, and sometimes determine the prognosis of the disease in advance. This applies, for example, to autoimmune hemolytic anemia with cold agglutinins.

In cases where antibodies are directed against antigen I, the disease is much more severe than when they are directed against antigen i.

Antigen I is present on the erythrocytes of adults in large quantities, and antigen i is present in small quantities. Therefore, the degree of agglutinability of erythrocytes in the presence of antibodies to antigen i is small. Despite a sharp increase in ESR up to 70-80 mm / h, a high titer of antibodies, the prognosis with such specificity of antibodies is good.

Also, determining the specificity of cold agglutinins can help diagnose the underlying disease, which was complicated by the cold form of autoimmune hemolytic anemia. So, in the idiopathic form of cold hemagglutination, antibodies are most often directed against antigen I, and in lymphosarcoma, macroglobulinemia - against antigen i. These antibodies differ not only in their specificity, but also in structure. So, in the idiopathic form of the disease, antibodies most often have light ᴂ-chains, and in lymphosarcoma, light λ-chains.

In infections, antibodies are most often polyclonal, have both types of light chains, and are directed against antigen i. Cold antibodies react not only with erythrocytes, but also with lymphocytes. Antibodies directed against antigen i react predominantly with B lymphocytes, and antibodies directed against antigen I with T lymphocytes, although a small amount of antigen i is present on B lymphocytes and antigen I on T lymphocytes.

In some cases of autoimmune hemolytic anemia with cold agglutinins, antibodies are directed against the Pr antigen, which is destroyed by papain and neuramininase. Such antibodies most often belong to the IgA class.

The type of hemolysis is usually extravascular. Direct antiglobulin bodies (Coombs' test) allows a diagnosis to be made and a cause to be suggested. Treatment depends on the cause and may include the use of corticosteroids, intravenous immunoglobulins, immunosuppressants, splenectomy, refusal of blood transfusions, and withdrawal of certain drugs are also required.

Causes of autoimmune hemolytic anemia

Hemolysis occurs mainly in the spleen. It is often severe and can be fatal. Most of heat autoantibodies refers to IgG. They are panagglutinins and most often have limited specificity.

Cold agglutinin disease is caused by autoantibodies that react at temperatures<37 °С. Иногда они образуются при инфекционных заболеваниях, лимфопролиферативных состояниях; около 1/2 всех случаев (в основном у пожилых) относятся к идиопатическим. При инфекционном генезе существует тенденция к острому течению, в то время как для идиопатического заболевания характерно хроническое течение. Наблюдается преимущественно вне-сосудистый гемолиз, который осуществляется мононуклеарной фагоцитарной системой печени. Анемия, как правило, не достигает тяжелой степени (Нb >7.5 g / dl). Cold autoagglutinins are usually IgM.

Paroxysmal cold hemoglobinuria refers to a rare type of cold agglutinin disease. Hemolysis occurs when exposed to cold, even local (drinking cold drinks, washing hands in cold water). It is observed in some patients with congenital or acquired syphilis. The severity of anemia and the rate of its development varies, fulminant course may be observed.

Symptoms and signs of autoimmune hemolytic anemia

In severe cases, fever, chest pain, fainting, and heart failure may occur. Mild splenomegaly is characteristic.

Cold agglutinin disease manifests itself as acute or chronic hemolytic anemia. Other manifestations of increased cold sensitivity (acrocyanosis, Raynaud's syndrome, occlusive lesions associated with cold) may be present. Hepatosplenomegaly may be present.

Diagnostics of the autoimmune hemolytic anemia

• The range of studies for the detection of hemolytic anemia.
• Direct antiglobulin test.

AIHA should be suspected in patients with hemolytic anemia, especially those with severe disease or other characteristic symptoms... Routine laboratory test results indicate the presence of extravascular hemolysis (no hemosiderinuria; haptoglobin levels close to normal), except in cases of severe acute or UGS-related symptoms. The presence of spherocytosis and an increase in MCHS are typical.

The diagnosis of AIHA is based on an antiglobulin test. Antiglobulin serum is added to the washed erythrocytes of the patient; agglutination indicates the presence of immunoglobulins or complement (C) associated with erythrocytes. As a rule, hemolytic anemia with warm antibodies is characterized by the presence of IgG, while cold antibody disease is characterized by the presence of C3. This test has<98% чувствительность в отношении диагностики АИГА. Как правило, положительный непрямой антиглобулиновый тест в сочетании с отрицательным прямым тестом означает наличие аллоантител, обусловленных беременностью, предшествующими гемотрансфузиями, перекрестной лектиновой активностью, а не иммунным гемолизом.

After the diagnosis of AIHA with the Coombs test is made, further testing is required.

There are three options:

• The reaction is positive for anti-IgG and negative for anti-SZ. This variant occurs with idiopathic and drug a (in response to the use of α-methyldopa) AIHA, and it is also usually characteristic of hemolytic anemia due to the presence of warm antibodies.
• The reaction is positive for anti-IgG and anti-C3. This variant occurs in SLE and idiopathic AIHA. This option is not observed in drug-induced anemia.
• The reaction is positive for anti-C3 and negative for anti-lgG. This option is observed with cold agglutinin disease. However, it is rare in idiopathic LIGA, hemolytic anemia due to the presence of warm antibodies (low affinity IgG), some drug-induced cases of the disease, and UGH.

There are other studies that suggest a cause for AIHA, but they are not diagnostically significant. In cold agglutinin disease, erythrocytes are located in the peripheral blood smear in the form of clusters. Related to this is the fact that automatic cell counts often reveal an increase in MCV and an apparent decrease in hemoglobin levels; when the vessel is heated with hands and the subsequent calculation of the indicators, their significant approximation to the norm is observed.

Treatment of autoimmune hemolytic anemia

Corticosteroids are the therapy of choice for warm antibody-mediated idiopathic AIHA. In extremely severe hemolysis, an introductory dose of 100-200 mg is recommended. With the stabilization of the number of red blood cells, corticosteroids are gradually canceled. If corticosteroid therapy is ineffective or relapses after discontinuation, splenectomy is performed. In approximately V 3 -V 2 cases, a sustained response to treatment is observed after splenectomy. For fulminant hemolysis, plasmapheresis is used. In less severe but uncontrolled hemolysis, temporary improvement may be provided by immunoglobulin infusions. If corticosteroid therapy and splenectomy are ineffective, long-term use of immunosuppressants (including cyclosporine) is required.

Cold agglutinin disease. In the acute course of the disease, treatment is mainly supportive, since anemia can be self-limiting. In chronic cases, anemia is often controlled by treating the underlying disorder. However, in idiopathic chronic disease, mild anemia (Hb 9-10 g / dL) may persist throughout life. Avoiding exposure to cold also results in significant improvement. Splenectomy is ineffective. The effectiveness of immunosuppressants is moderate. Blood transfusions should be performed carefully, with blood preheating. Since autologous erythrocytes already have resistance to autoantibodies, their lifespan is longer than donor cells, which limits the effectiveness of blood transfusion.

A prerequisite for UGS therapy is strict avoidance of exposure to cold. Splenectomy does not improve. Immunosuppressants can be effective, but their use should be limited in patients with advanced or idiopathic illness. Simultaneous anti-syphilitic treatment can help cure UGS.