Autoimmune hemolytic anemia treatment. Hemolytic anemia

When a large production of antibodies begins in the body, the destruction of red blood cells occurs. In my own words, my own body destroys its own cells. This is due to a decrease in hemoglobin levels. The danger lies in the fact that as a result of these antibodies, red blood cells cease to function, and sticking together, form a blockage of the vessels of the entire circulatory system.

There are two types of autoimmune hemolytic anemia:

There are two forms of this hemolytic anemia;

Reasons for development

How to diagnose the disease

How to prevent illness

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

Why does pathology appear and what are its types?

Like many ailments, autoimmune hemolytic anemia is formed against the background of improper functioning of the immune system. The reasons for this may be damaged sections of DNA or genetic changes. This disease can also be hereditary. This is due to the ability of DNA to retain information in itself and be passed on to the next generation.

The development of the disease may also be associated with the period of bearing a child if there is an incompatibility of the Rh factors in the blood of a pregnant woman and the fetus.

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

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

According to the method of studying the antibodies of the immunity of the 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 form with incomplete thermal agglutinin is most often diagnosed, its frequency ranges from 70 to 80% of all autoimmune anemias.

Such anemias are also classified according to the clinical picture of their course. According to this gradation, they can be acute and chronic. The first form is characterized by an abrupt onset. A 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 severe or mild symptoms:

1. The acute form is characterized by a sharp onset. The patient complains of sudden weakness, fever. As a result, his skin takes on a yellowish tint. The patient may notice shortness of breath and paroxysmal manifestations of the heartbeat.
2. Chronic autoimmune hemolytic anemia, whose symptoms often do not appear so sharply 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 sign 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 feels the edges of the enlarged spleen, and sometimes the liver.

Autoimmune anemia, which is associated with an allergy to cold, is characterized by the patient's severe non-perception of sub-zero temperatures. At the same time, urticaria develops, and the course of the disease itself is characterized by frequent exacerbations. In the analyzes, characteristics of hemoglobinuria, normocytosis, normochromic or hyperchromic anemia are observed. A feature of cold autoimmune anemia is also the gluing of red blood cells in the analysis, which disappears when warmed. The deterioration of the well-being of such patients also occurs during the addition of viral infections.

Features of diagnosis

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).

Such an 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 only indicates the absence of antibodies in close proximity to red blood cells, but at the same time it is an indirect test that can indicate the circulation of antibodies in the plasma (we are talking about free immune cells).

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

Characteristic features will be:

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

During the biochemistry of the 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 - will necessarily increase in the blood, which indicates inflammatory processes in the body.

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

Also, the disease has some similarities with such an ailment as sickle cell type of hemolytic anemia. Massive death of erythrocytes is noted here, 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 disease is diagnosed in childhood. Therefore, it is very important to conduct a correct diagnosis and recognize the true cause of the death of red blood cells in the patient's body.

Features of the treatment of the disease

Autoimmune hemolytic anemia, the treatment of which should be under the strict supervision of a hematologist, in most cases is eliminated by the use of hormonal drugs from the group of corticosteroids. This is the most commonly used method today. The action of these drugs is focused on reducing the body's production of antibodies, which leads to a normalization of the immune response.

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

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

The therapy of autoimmune hemolytic anemia is a very complex and lengthy work, after stabilization of the main indicators, it is necessary to leave the patient on maintenance treatment for another two to three months.

Usually for this period the daily dose of the hormone is not 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 of 4 to 6 hours. It is used to relieve DIC, which often develops in the human body as the number of red blood cells in the blood decreases. The drug is administered subcutaneously, every six hours under constant monitoring of blood counts (coagulogram).
• Nadroparin is a drug that is similar in its actions to the human body with Heparin. But its main characteristic is a longer effect, which ranges from 24 to 48 hours. Assign subcutaneous injection of 0.3 ml / day.

• Folic acid is a group of vitamins. It is actively involved in the processes of the body, among which are the processes of formation of red blood cells. 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 the process of blood clots and the onset of DIC. In addition to this action, the drug improves blood circulation in the tissues of the systems and organs of the patient. The required therapy with this medicine is at least three months.
• B12 is a vitamin that takes an active part in the final formation of an erythrocyte. 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 an antihistamine drug. Its main action is to reduce the functionality of the stomach in the production of hydrochloric acid. Why is this important in the treatment of hemolytic autoimmune anemia? These measures are necessary because they smooth out the side effects of the drugs needed for therapy (Prednisolone). The recommended dose is 150 mg twice daily.

It is not uncommon for the patient's body to resist the action of a course of hormone therapy. In this case, the disease begins to progress with frequent acute clinical manifestations. If a positive response cannot be obtained, then surgery is often prescribed, in which the spleen is resected. This operation is called a splenectomy. Due to this removal, it is possible to achieve a decrease in the content of antibodies in the blood that 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 channels are ligated and the organ is removed. After that, the doctor makes an audit of the 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 does not exist. If a check is not carried out, and the patient ends up 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 carried out by residual additional spleens.

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

These drugs include:

• Cyclosporine A - administered intravenously using a dropper, 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 must be stopped by infusion therapy (saline solutions), transfusion of the 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 for vital signs (soporous complication). At the same time, it is important to select donor transfusions with a mandatory Coombs test.

Forecast and prevention

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

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

They are divided into primary and secondary:

1. The main impact 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 who have developed and progressed the disease.

In the case of idiopathic autoimmune anemia, there are no primary preventive measures, since the patient does not have the causes that cause its appearance. 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.

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

After the therapy, which is accompanied by a 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 to repeat all the necessary diagnostic methods, and the need for further therapy is determined by their indicators. Such control helps to detect the onset of relapse in time and stop it in the early stages.

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

Statistical data also speaks 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 efficiency increases to 80%;
• higher rates can be achieved by immunosuppressive therapy (up to 95%).

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

Acquired hemolytic anemia, in which increased destruction of erythrocytes is the result of the destructive effect of autoantibodies directed against unchanged antigens of the membrane of the patient's own erythrocytes, are called autoimmune.

It is assumed that, as in other autoimmune diseases, the causes of the production of anti-erythrocyte autoantibodies lie in a violation of the body's immune system, in particular, in a violation of the ability of the suppressor T cell to control autoimmune or "forbidden" B-lymphocyte clones capable of producing antibodies. against self antigens.

The frequency of AIHA is 1:80,000 of the population, women are more often ill.

The course and prognosis of AIHA is largely determined by the type of autoantierythrocyte antibodies circulating in the patient's blood.

Autoimmune antibodies have the structure more often than IgG, less often - IgM and IgA. They may be most active at high body temperature (warm antibodies) or at low temperatures (cold antibodies), or be fixed on erythrocytes at low temperature, and have a damaging effect at body temperature ( biphasic Donat-Landsteiner antibodies).

According to the mechanism of damaging action, anti-erythrocyte antibodies are divided into:

agglutinins causing gluing (agglutination) of erythrocytes;

hemolysins , causing the destruction (lysis) of erythrocytes with the participation of the activated complement system;

opsonins that promote phagocytosis of erythrocytes.

Depending on the serological characteristics, two main types of agglutinins are distinguished: complete and incomplete.

Complete agglutinins cause agglutination of erythrocytes in any medium: water-salt or colloidal. Most complete agglutinins are IgM. Due to the large size of the IgM autoantibodies molecules, they are able to overcome the negative electrostatic interaction between erythrocytes, therefore, even in a saline environment, serum containing complete IgM agglutinins causes erythrocytes to stick together if antigens are present on their surface, against which these IgM autoantibodies are directed.

Incomplete antibodies more often have the structure of IgG or IgA and are unable to cause erythrocyte agglutination in a water-salt environment. Bonding of erythrocytes by incomplete antibodies can occur only in a colloidal medium, in cases where they manage to change the electrostatic forces that cause the repulsion of erythrocytes. In patients with autoimmune hemolytic anemia caused by incomplete agglutinins, antibodies are fixed on the surface of erythrocytes to the corresponding antigen (more often the Rh system), causing their sensitization, but not the process of intravascular gluing (agglutination).

Hemolysins are less common than agglutinins. Depending on the temperature optimum, there are thermal,cold and two-phase hemolysins. Most hemolysins belong to the IgG type, less often - to IgM and IgA. Being fixed on the surface of erythrocytes that have the corresponding antigen against which antibodies are directed, hemolysins cause the destruction of erythrocytes, mainly through the activation of the complement system, the components of which have a proteolytic effect.

Opsonins called antibodies that promote phagocytosis of erythrocytes by monocytes and macrophages. Opsonins are usually detected simultaneously with cold hemolysins. Opsonins are detected by erythrophagocytosis, which occurs after incubation of the test blood with the patient's serum.

AIHAs are subdivided into distinct variants depending on the serologic features or the type of autoantibodies that cause them. In addition, in each serological variant, idiopathic and symptomatic forms are distinguished, which occur in patients who already have other diseases.

AIGA classification.

AIHA with incomplete heat agglutinins:

idiopathic;

symptomatic in patients with lymphoproliferative diseases (chronic lymphocytic leukemia, lymphomas), SLE, RA, periarteritis nodosa, ovarian tumors, thyroid disease.

AIHA with thermal hemolysins:

idiopathic;

symptomatic in patients with myelofibrosis and chronic lymphocytic leukemia.

AIHA with complete cold agglutinins:

idiopathic;

symptomatic in patients after viral pneumonia, infectious mononucleosis, in patients with lymphoproliferative diseases, Waldenström's macroglobulinemia, monoclonal gammopathy and in patients with chronic hepatitis.

AIHA with biphasic cold hemolysins of the Donat-Landsteiner type:

idiopathic;

symptomatic in patients with advanced forms of syphilis, with viral infections (cytomegalovirus).

AIHA with incomplete thermal agglutinins.

AIHA with incomplete heat agglutinins is the most common form (80-85%) of this type of hemolytic anemia. AIHA with incomplete heat agglutinins (HTA) occurs in all age groups, but is more common in middle-aged people, with a frequency of 1:80,000 of the population. Among patients there is a certain predominance of women (55-60%). Idiopathic and symptomatic forms occur with equal frequency.

Clinic.

AIHA with NTA, as a rule, begins gradually and is characterized by slowly progressive pallor, yellowness of the skin and mucous membranes, and sometimes subfebrile temperature. In connection with the gradual adaptation of the patient to a slow decrease in the level of hemoglobin, the general condition of the patient suffers slightly. Less common is an acute and subacute onset of the disease with a decrease in hematocrit by 5% or more every 24 hours, while jaundice quickly increases, general weakness, cyanosis, shortness of breath, tachycardia and other signs of cardiovascular insufficiency appear. In the future, the disease, as a rule, acquires a chronic course, in which episodes of increased hemolysis are replaced by a state of clinical and hematological compensation. Recurrent hemolysis can be triggered by infections, surgery, and pregnancy.

A slight increase in the liver is observed in 1/2-1/3 of patients, and a moderate increase in the spleen - in more than ½ of patients.

The mechanism of hemolysis in AIHA with NTA is intracellular in nature, i.e. the destruction of erythrocytes is carried out by macrophages with receptors for Ig. Since autoantibodies have their own Ig structure, macrophages phagocytize those erythrocytes on the surface of which antibodies are fixed, more often of the IgG type. Whole erythrocytes (erythrophagocytosis) or their fragments can be subjected to phagocytosis. In the latter case, erythrocytes decrease in size and take the form of microcytes.

The most intense intracellular hemolysis occurs in the spleen, where in the sinuses there is a physiological slowdown in blood flow and, consequently, the duration of contact between sensitized erythrocytes and macrophages lining the walls of the sinuses is lengthened.

A similar type of intracellular hemolysis occurs in AIHA with NTA in the liver, bone marrow, and other organs rich in macrophages.

Laboratory data.

Anemia in AIHA with NTA is normochromic and slightly macrocytic (due to the increased content of reticulocytes, which are larger in size than normocytes). When viewing a blood smear, there is a noticeable polychromasia and anisocytosis, the presence of microspherocytes and normoblasts (especially in patients with active hemolysis). The phenomenon of autoagglutination is rarely observed. The content of reticulocytes is increased. The lifespan of erythrocytes is shortened.

Osmotic resistance due to changes in the properties of the membrane by fixed autoantibodies is usually reduced, which also explains the spherocytosis of erythrocytes.

The number of leukocytes is most often slightly increased during hemolytic crises. The platelet count is normal or slightly reduced. In the presence, in addition to anti-erythrocyte, also platelet antibodies ( Fisher-Ivens syndrome) develops concomitant deep thrombocytopenia, severe to cause severe hemorrhagic complications.

In the bone marrow, pronounced hyperplasia of the red hematopoietic germ is found, sometimes with megaloblastic features, due to the relative insufficiency of folates, the consumption of which by actively proliferating normoblasts is significantly increased.

In plasma, hyperbilirubinemia is determined due to the non-conjugated (indirect) fraction; in the feces, the amount of stercobilin increases, and in the urine - urobilin.

Diagnosis and differential diagnosis.

The diagnosis of AIHA with NTA is based on the detection of clinical and laboratory signs of acquired intracellular hemolysis and positive results of the direct antiglobulin Coombs test.

The Coombs test detects antibodies fixed on erythrocytes using an antiglobulin antiserum obtained by immunizing animals with the globulin fraction of human plasma. Animal antiglobulin antiserum contains antibodies (such as total agglutinins) directed against human globulins. Since autoantibodies in AIHA with NTA, which are fixed on the surface of erythrocytes in their structure, are globulins, under the action of antiglobulin serum in a saline medium, agglutination of sensitized erythrocytes occurs, which confirms the presence of autoantibodies on their surface and the diagnosis of AIHA with NTA.

A negative direct Coombs test, however, does not exclude the presence of AIHA with NTA, but may also indicate a low density of autoantibodies on the erythrocyte surface (less than 200 molecules). In these cases, more sensitive tests are used to confirm the diagnosis: a trypsin or papain-Coombs test and an aggregate-hemaglutination test, the resolution of which is more than 100 times higher than that of a standard direct Coombs test.

Differentiate AIHA with NTA is sometimes associated with drug-induced immune hemolytic anemias (LIHA), in which a direct Coombs test may also be positive. LIGA is based on a change in the antigenic structure of the erythrocyte membrane under the influence of a drug - hapten, which results in the appearance of a new antigen on the erythrocyte and, as a result, the production of antibodies to it. Among the drugs that can cause immune hemolysis, we should mention α-methyldopa, cephalosporins, rifampicin, analgin, quinidine, paracetamol, etc. Therefore, in all patients with a positive direct Coombs test, collecting an anamnesis, it is necessary to exclude long-term use of drugs, the abolition of which is usually leads to the cessation of hemolysis and makes the Coombs test negative.

Treatment.

The main treatment for AIHA with NTA is the administration of corticosteroids (prednisolone or its analogues). On average, 1 mg of prednisolone is used per kg of the patient's weight (60-80 mg / day). At this dose, prednisolone is prescribed until hemoglobin levels normalize, jaundice and other laboratory signs of hemolysis disappear, which is sometimes accompanied by a negative result of the direct Coombs test. Then the dose of prednisolone is gradually reduced by 0.5-1 tab. in 2-3 days until complete cancellation. Treatment with prednisolone leads to normalization of hemoglobin concentration in 75% of patients, although the direct Coombs test may remain positive.

If corticosteroids are ineffective, which becomes clear within 2 weeks of observation of the patient, or if hemolysis recurs after its cancellation, splenectomy is indicated, which can lead to a complete recovery of the patient or allow to increase the intervals between courses of corticosteroid therapy.

For the treatment of patients resistant to prednisolone and in the absence of the effect of splenectomy, cytostatics, immunosuppressants are used: imuran or 6-mercaptopurine at a dose of 100-150 mg per day, cyclophosphamide at a dose of 200 mg / day, chlorbutine 5-10 mg / day, cyclosporine 5 mg / kg / day, etc. In most cases, immunosuppressive therapy leads to an improvement in hematological parameters, however, persistent remission is observed infrequently.

In recent years, in the treatment of resistant forms of AIHA, monoclonal antibodies to CD20 have been used - Rituximab (MabThera) intravenously 375 mg/m 2 once a week for 4 weeks, the remission rate reaches 55-80%, maintenance therapy is usually not required. In severe cases, plasmapheresis may be used.

A positive effect is sometimes exerted by intravenous administration of large doses of immunoglobulins that neutralize autoantibodies and their effect on red blood cells. Unfortunately, the abolition of intravenous administration of immunoglobulins is accompanied by a relapse of the disease.

In cases of profound anemia with symptoms of hypoxia, only a specially selected red blood cell mass can be transfused to patients with AIHA with NTA. For this purpose, at blood transfusion stations or blood banks, erythrocytes of donors (usually from 15-20 people) are incubated (each sample separately) in the patient's plasma at 37 0 C. After that, a direct Coombs test is performed with each sample of donor erythrocytes. In case of agglutination of donor erythrocytes with antiglobulin antiserum, they cannot be used for transfusion, because the membrane of donor erythrocytes contains the same antigens against which antibodies are directed in the patient's plasma. You can transfuse only those donor erythrocytes that, after incubation in the patient's plasma, gave a negative direct Coombs test.

Course and forecast.

AIHA with NTA is characterized by an undulating course with alternating clinical well-being and relapses of the disease. The duration of the disease ranges from several months to many years. In ¼ of patients, a complete recovery occurs with a persistent transition from a positive Coombs test to a negative one.

AIHA with total thermal hemolysins (TG).

AIHA due solely to hemolysins is rare. More often, thermal hemolysins are found in patients with AIHA with NTA, which significantly worsens the prognosis for this disease.

Clinic.

AIHA with TG can occur both acutely and chronically. Ictericity of the skin and mucous membranes is expressed slightly. During hemolysis, pain in the abdominal cavity and an increase in body temperature are possible. During the hemolytic crisis, thrombosis of various localizations can develop.

The liver and spleen are usually not enlarged. Since the destruction of erythrocytes by thermal hemolysins occurs with the active participation of activated complement inside the vessels, clinical manifestations include the appearance of black urine due to the content of oxidized hemoglobin in it or hemoglobinuria. In chronic intravascular hemolysis in an AIHA patient with TG, hemosiderin is also present in the urine.

Laboratory data.

Normochromic normocytic anemia, reticulocytosis. In plasma, the level of free hemoglobin increases and the concentration of haptoglobin decreases. In the urine - hemoglobinuria and hemosiderinuria. Participation of complement in the processes of hemolysis in AIHA with TG leads to a decrease in complement activity, and complement components C3, C4, C9 can be detected in a fixed state on the surface of erythrocytes using anticomplementary antiserum.

Diagnostics.

The Coombs test in patients with hemolysin AIHA is usually negative. This disease is diagnosed by an autohemolysis test: the patient's blood, taken with citrate, is placed in a thermostat at 37 0 C. After 30-40 minutes, reddening of the plasma occurs due to the destruction of erythrocytes by the thermal autohemolysins present in the plasma.

Treatment.

In the treatment of AIHA with TG, corticosteroids and immunosuppressants are being tried. Sometimes there is a development of long-term remission, however, complete recovery is rare.

Forecast.

The prognosis of hemolysin AIHA depends on the frequency and intensity of hemolysis episodes.

Autoimmune hemolytic anemia with complete cold agglutinins.

AIHA with complete cold agglutinins (CHA), or cold agglutinin disease (CAD), occurs mainly in the elderly. Symptomatic forms of CAB are more common in patients with chronic lymphocytic leukemia, Waldenström's macroglobulinemia, malignant lymphomas and monoclonal gammopathy. In young people, CAB may appear after infectious mononucleosis, mycoplasmal pneumonia. CAB accounts for about 10-20% of all cases of AIHA. Slightly more often than HAB women are ill.

Clinic.

HAB is characterized by a chronic course. The disease begins gradually: a characteristic feature of the disease is poor tolerance to cold, under the influence of which patients develop "acrocyanosis" in the form of blue and blanching of the skin of the fingers, ears and nose. A change in skin color may be accompanied by a violation of sensitivity and the appearance of pain. These symptoms, characteristic of Raynaud's syndrome, are usually reversible: they disappear as soon as the patient enters a warm room. However, with a long stay in the cold, gangrene may develop in places where the body is cooled. The activity of hemolysis in CAB, as a rule, is low, therefore, there may be only slight icterus of the skin and mucous membranes, the liver and spleen are usually not enlarged. The destruction of agglutinated erythrocytes is carried out by macrophages, i.e. hemolysis is intracellular in nature.

Laboratory data.

Anemia is usually normochromic and normocytic in nature, and the hemoglobin level drops sharply to 80 g/l. When viewing blood smears, the expressed spontaneous autoagglutination of erythrocytes attracts attention, which makes it difficult to count them.

Diagnosis and differential diagnosis.

The diagnosis of CAP is based on the ability of the patient's serum to cause agglutination of group 0 donor erythrocytes in cold conditions. the degree of dilution at which the ability of the patient's serum to agglutinate erythrocytes is preserved ranges from 1:1000 to 1:1000000. The titer of agglutinins and the temperature optimum of their action largely determines the clinical picture of the disease. Cold agglutinins are IgM and are usually directed against type I/i erythrocyte membrane antigens.

It is often necessary to differentiate CAB with diseases accompanied by impaired microcirculation in the cold: cryoglobulinemia and Raynaud's syndrome of vascular origin, often complicating rheumatic diseases (rheumatoid arthritis).

Treatment.

Splenectomy and corticosteroids are usually ineffective in CAP. Positive results are obtained by the use of immunosuppressants (chlorbutin, cyclophosphamide). Although the need for blood transfusions in CAB is relatively rare, it should be remembered that patients with this disease can only be transfused with saline-washed erythrocytes that do not contain complement on their surface.

In most cases, simple measures such as avoiding contact with cold, warming the patient and bed rest give a good effect.

Course and forecast.

The course of CAP is relatively benign, with periods of worsening in winter and almost complete disappearance of symptoms in summer. There is practically no complete recovery from CAB, and together, cases of death are extremely rare.

In symptomatic forms of CAB, the prognosis is mainly determined by the underlying disease.

Autoimmune hemolytic anemia with biphasic cold hemolysins or paroxysmal cold hemoglobinuria (PCH).

UGS is one of the most rare types of AIHA. UCH is characterized by episodes (paroxysms) of intravascular hemolysis, hemoglobinuria, which are provoked by cooling.

PCG is caused by IgG-type antibodies, usually directed against the P-antigen of erythrocytes and which are fixed on them at low temperature. Hemolysis occurs with the participation of complement at body temperature.

Donat and Landsteiner at the beginning of the 20th century identified a causal relationship between advanced syphilis, especially its congenital form, and UCH. It has now been established that the role of syphilis in the development of PCG is small, however, this disease can complicate the course of some acute viral infections (measles, rubella, infectious mononucleosis, etc.) or occur without an established cause (idiopathic form).

Clinic.

PCG occurs in all age groups, but is more common in children. Both sexes are affected with equal frequency. The most characteristic feature of UCH is the appearance of black urine after local or general hypothermia, especially for a sufficiently long time.

The disease begins acutely: a few minutes or hours after hypothermia, muscle pains, pains in the abdominal cavity, general weakness, vomiting and a tremendous chill with an increase in body temperature to febrile numbers appear. During this attack, or soon after, black urine is expelled. In the future, yellowness of the skin and sclera appears. With erased forms, which are observed in ½ of patients, all these symptoms are much less pronounced.

Laboratory data.

Anemia develops only during a hemolytic crisis. The severity of anemia and reticulocytosis depend on the intensity and frequency of hemolysis paroxysms.

The concentration of free hemoglobin in the blood increases (during a crisis). In the urine - hemoglobinuria, hence - its black staining.

Diagnostics.

The presence of biphasic autoantibodies of the Donat-Landsteiner type can be established by hemolysis at 37°C of pre-chilled blood, which is manifested by reddening of the plasma (Donat-Landsteiner test). It has been established that biphasic hemolysins, unlike cold agglutinins, are rarely present in the blood in high titer.

The Coombs test, if carried out at a low temperature, will be positive, and under standard conditions, the results of this test are negative.

Treatment.

In symptomatic forms of PCG, as a rule, spontaneous recovery is observed as the underlying disease is cured. In the treatment of idiopathic forms, the most important role is played by preventive measures aimed at preventing hypothermia.

Corticosteroids and splenectomy are ineffective in PCH.

What is Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemias include forms of the disease associated with the formation of antibodies to self-antigens of erythrocytes.

In the general group of hemolytic anemias, autoimmune hemolytic anemias are more common. Their frequency is 1 case per 75,000-80,000 population.

What Causes Autoimmune Hemolytic Anemia?

Immune hemolytic anemia can occur under the influence of anti-erythrocyte iso- and autoantibodies and, accordingly, are divided into isoimmune and autoimmune.

Isoimmune include hemolytic anemia of newborns, due to incompatibility in the ABO and Rh systems between the mother and fetus, post-transfusion hemolytic anemia.

With autoimmune hemolytic anemia, there is a breakdown of immunological tolerance to unchanged antigens of one's own erythrocytes, sometimes to antigens that have determinants similar to erythrocytes. Antibodies to such antigens are able to interact with unchanged antigens of their own erythrocytes. Incomplete heat agglutinins are the most common type of antibody that can cause the development of autoimmune hemolytic anemia. These antibodies belong to IgG, rarely - to IgM, IgA.

Immune hemolytic anemias are divided into isoimmune and autoimmune. The serological principle of differentiation of autoimmune hemolytic anemia makes it possible to distinguish forms caused by incomplete thermal agglutinins, thermal hemolysins, cold agglutinins, biphasic cold hemolysins (Donat-Landsteiner type) and erythroopsonins. Some authors distinguish a form of hemolytic anemia with antibodies against the antigen of bone marrow normoblasts.

According to the clinical course, acute and chronic variants are distinguished.

There are symptomatic and idiopathic autoimmune hemolytic anemias. Symptomatic autoimmune anemia occurs against the background of various diseases accompanied by disorders in the immunocompetent system. Most often they occur in chronic lymphocytic leukemia, lymphogranulomatosis, acute leukemia, systemic lupus erythematosus, rheumatoid arthritis, chronic hepatitis and liver cirrhosis. In cases where the appearance of autoantibodies cannot be associated with any pathological process, they speak of idiopathic autoimmune hemolytic anemia, which accounts for about 50% of all autoimmune anemias.

The formation of autoantibodies occurs as a result of a violation in the system of immunocompetent cells that perceive the erythrocyte antigen as foreign and begin to produce antibodies to it. After fixation of autoantibodies on erythrocytes, the latter are captured by cells of the reticulohistiocytic system, where they undergo agglutination and decay. Hemolysis of erythrocytes occurs mainly in the spleen, liver, and bone marrow. Autoantibodies to erythrocytes belong to different types.

According to the serological principle, autoimmune hemolytic anemias are divided into several forms:
- anemia with incomplete heat agglutinins
- anemia with thermal hemolysins
- anemia with complete cold agglutinins
- anemia with biphasic hemolysins
- anemia with agglutinins against bone marrow normoblasts

Each of these forms has some features in the clinical picture, course and serological diagnosis. The most common anemia with incomplete thermal agglutinins, accounting for 70 - 80% of all autoimmune hemolytic anemia.

Pathogenesis (what happens?) during Autoimmune Hemolytic Anemia

The essence of autoimmune processes is that as a result of the weakening of the T-suppressor system of immunity, which controls autoaggression, the B-system of immunity is activated, synthesizing antibodies against unchanged antigens of various organs. T-lymphocytes-killers also take part in the implementation of autoaggression. Antibodies are immunoglobulins (Ig), most often belonging to class G, less often - M and A; they are specific and directed against a particular antigen. IgM include, in particular, cold antibodies and biphasic hemolysins. An erythrocyte carrying antibodies is phagocytosed by macrophages and destroyed in them; possible lysis of erythrocytes with the participation of complement. Antibodies of the IgM class can cause agglutination of erythrocytes directly in the bloodstream, and antibodies of the IgG class can only destroy erythrocytes in spleen macrophages. In all cases, hemolysis of erythrocytes occurs more intensely, the more antibodies are on their surface. Hemolytic anemia with antibodies to spectrin has been described.

Symptoms of autoimmune hemolytic anemia

With an acute onset of autoimmune hemolytic anemia, patients develop rapidly increasing weakness, shortness of breath and palpitations, pain in the heart area, sometimes in the lower back, fever and vomiting, intense jaundice. In the chronic course of the process, a relatively satisfactory state of health of patients is noted even with deep anemia, often severe jaundice, in most cases an increase in the spleen, sometimes the liver, alternating periods of exacerbation and remission.

Anemia is normochromic, sometimes hyperchromic, with hemolytic crises usually marked by severe or moderate reticulocytosis. Macrocytosis and microspherocytosis of erythrocytes are found in the peripheral blood, the appearance of normoblasts is possible. ESR is increased in most cases. The content of leukocytes in the chronic form is normal, in the acute form, leukocytosis occurs, sometimes reaching high numbers with a significant shift of the leukocyte formula to the left. The platelet count is usually normal.
In Fisher-Evens syndrome, autoimmune hemolytic anemia is combined with autoimmune thrombocytopenia. In the bone marrow, erythropoiesis is enhanced, megaloblasts are rarely detected. In most patients, the osmotic resistance of erythrocytes is reduced, which is due to a significant number of microspherocytes in the peripheral blood. The content of bilirubin is increased due to the free fraction, and the content of stercobilin in feces is also increased.

Incomplete heat agglutinins are detected using a direct Coombs test with polyvalent antiglobulin serum. With a positive test using antisera to IgG, IgM, etc., it is specified to which class of immunoglobulins the detected antibodies belong. If there are less than 500 fixed IgG molecules on the surface of red blood cells, the Coombs test is negative. A similar phenomenon is usually observed in patients with a chronic form of autoimmune hemolytic anemia or who have undergone acute hemolysis. Coombs-negative are also cases when antibodies belonging to IgA or IgM are fixed on erythrocytes (in relation to which polyvalent antiglobulin serum is less active).
Approximately 50% of cases of idiopathic autoimmune hemolytic anemia simultaneously with the appearance of immunoglobulins fixed on the surface of erythrocytes, antibodies to their own lymphocytes are detected.

Hemolytic anemia due to thermal hemolysins, is rare. It is characterized by hemoglobinuria with black urine, alternating periods of acute hemolytic crisis and remissions. The hemolytic crisis is accompanied by the development of anemia, reticulocytosis (in some cases, thrombocytosis) and an enlarged spleen. There is an increase in the level of free fraction of bilirubin, hemosiderinuria. When treating donor erythrocytes with papain, it is possible to detect monophasic hemolysins in patients. Some patients have a positive Coombs test.

Hemolytic anemia due to cold agglutinins(cold hemagglutinin disease) has a chronic course. It develops with a sharp increase in the titer of cold hemagglutinins. There are idiopathic and symptomatic forms of the disease. The leading symptom of the disease is excessive sensitivity to cold, which manifests itself in the form of blue and whitening of the fingers and toes, ears, nose tip. Disorders of the peripheral circulation lead to the development of Raynaud's syndrome, thrombophlebitis, thrombosis and trophic changes up to acrogangrene, sometimes cold urticaria. The occurrence of vasomotor disorders is associated with the formation of large intravascular conglomerates from agglutinated erythrocytes during cooling, followed by spasm of the vascular wall. These changes are combined with increased predominantly intracellular hemolysis. In some patients there is an increase in the liver and spleen. Moderately severe normochromic or hyperchromic anemia, reticulocytosis, normal leukocyte and platelet counts, increased ESR, a slight increase in the level of free fraction of bilirubin, a high titer of complete Cold agglutinins (detected by agglutination in a saline medium), sometimes signs of hemoglobinuria are observed. Characteristic is the agglutination of erythrocytes in vitro, which occurs at room temperature and disappears when heated. If it is impossible to perform immunological tests, a provocative test with cooling acquires diagnostic value (in the blood serum obtained from a finger tied with a tourniquet after lowering it into ice water, an increased content of free hemoglobin is determined).

In cold hemagglutinin disease, in contrast to paroxysmal cold hemoglobinuria, hemolytic crisis and vasomotor disorders occur only from hypothermia of the body and hemoglobinuria, which began in cold conditions, stops when the patient moves to a warm room.

The symptom complex characteristic of cold hemagglutinin disease can occur against the background of various acute infections and some forms of hemoblastoses. With idiopathic forms of the disease, complete recovery is not observed, with symptomatic forms, the prognosis depends mainly on the severity of the underlying process.

Paroxysmal cold hemoglobinuria is one of the rare forms of hemolytic anemia. It affects people of both sexes, more often children.

Patients with paroxysmal cold hemoglobinuria may experience general malaise, headache, body aches, and other discomfort after being in the cold. This is followed by chills, fever, nausea and vomiting. Urine turns black. At the same time, jaundice, enlargement of the spleen and vasomotor disorders are sometimes detected. Against the background of a hemolytic crisis, patients show moderate anemia, reticulocytosis, an increase in the content of the free fraction of bilirubin, hemosiderinuria and proteinuria.

The final diagnosis of paroxysmal cold hemoglobinuria is established on the basis of the detected two-phase hemolysins according to the Donat-Landsteiner method. It is not characterized by autoagglutination of erythrocytes, which is constantly observed in cold hemagglutination disease.

Hemolytic anemia due to erythroopsonins. The existence of autoopsonins to blood cells is generally recognized. With acquired idiopathic hemolytic anemia, cirrhosis of the liver, hypoplastic anemia with a hemolytic component and leukemia, the phenomenon of autoerythrophagocytosis was found.

Acquired idiopathic hemolytic anemia, accompanied by a positive phenomenon of autoerythrophagocytosis, has a chronic course. Periods of remission, sometimes lasting a considerable time, are replaced by a hemolytic crisis, characterized by icterus of visible mucous membranes, darkening of urine, anemia, reticulocytosis and an increase in the indirect fraction of bilirubin, sometimes an increase in the spleen and liver.

In idiopathic and symptomatic hemolytic anemia, the detection of autoerythrophagocytosis in the absence of data indicating the presence of other forms of autoimmune hemolytic anemia gives reason to attribute them to hemolytic anemia caused by erythroopsonins. Diagnostic test of autoerythrophagocytosis is carried out in direct and indirect versions.

Immunohemolytic anemia associated with the use of drugs. Various drugs (quinine, dopegyt, sulfonamides, tetracycline, tseporin, etc.) that can cause hemolysis form complexes with specific heteroantibodies, then settle on erythrocytes and attach complement to themselves, which leads to disruption of the erythrocyte membrane. This mechanism of drug-induced hemolytic anemia is confirmed by the detection of complement on the erythrocytes of patients in the absence of immunoglobulins on them. Anemia is characterized by an acute onset with signs of intravascular hemolysis (hemoglobinuria, reticulocytosis, an increase in the content of the free fraction of bilirubin, increased erythropoiesis). Against the background of a hemolytic crisis, acute renal failure sometimes develops.

Hemolytic anemia, which develops with the appointment of penicillin and methyldopa, proceed somewhat differently. Introduction per day of 15,000 units or more of penicillin can lead to the development of hemolytic anemia, characterized by intracellular hyperhemolysis. Along with the general clinical and laboratory signs of hemolytic syndrome, a positive direct Coombs test is also detected (the detected antibodies are related to IgG). Penicillin, binding to the antigen of the erythrocyte membrane, forms a complex against which antibodies are produced in the body.

With prolonged use of methyldopa, some patients develop a hemolytic syndrome that has the features of an idiopathic form of autoimmune hemolytic anemia. The detected antibodies are identical with thermal agglutinins and belong to IgG.

Hemolytic anemia due to mechanical factors, is associated with the destruction of red blood cells during their passage through altered vessels or through artificial valves. Vascular endothelium changes in vasculitis, malignant arterial hypertension; at the same time, adhesion and aggregation of platelets are activated, as well as the system of blood coagulation and thrombin formation. Widespread blood stasis and thrombosis of small blood vessels (DIC) develop with traumatization of red blood cells, as a result of which they are fragmented; numerous fragments of erythrocytes (schistocytes) are found in a blood smear. RBCs are also destroyed when they pass through artificial valves (more often with multi-valve correction); described hemolytic anemia on the background of senile calcified aortic valve. The diagnosis is based on signs of anemia, an increase in the concentration of free bilirubin in the blood serum, the presence of schistocytes in a peripheral blood smear, and symptoms of the underlying disease that caused mechanical hemolysis.

Hemolytic uremic syndrome(Moshkovich's disease, Gasser's syndrome) can complicate the course of autoimmune hemolytic anemia. The disease of an autoimmune nature is characterized by hemolytic anemia, thrombocytopenia, kidney damage. Disseminated lesions of vessels and capillaries are noted with the involvement of almost all organs and systems, pronounced changes in the coagulogram, characteristic of DIC.

Diagnosis of autoimmune hemolytic anemia

Diagnosis of autoimmune hemolytic anemia put on the basis of the presence of clinical and hematological signs of hemolysis and the detection of autoantibodies on the surface of erythrocytes using the Coombs test (positive in almost 60% of autoimmune hemolysis). Differentiate the disease from hereditary microspherocytosis, hemolytic anemia associated with enzyme deficiency.

In the blood - normochromic or moderately hyperchromic anemia of varying severity, reticulocytosis, normoblasts. In some cases, microspherocytes are found in blood smears. The number of leukocytes may increase during a hemolytic crisis. The platelet count is usually within the normal range, but thrombocytopenia may occur. ESR is significantly increased. In the bone marrow, there is marked hyperplasia of the erythroid germ. The content of bilirubin in the blood, as a rule, is increased due to indirect.

Treatment of autoimmune hemolytic anemia

In acute forms of acquired autoimmune hemolytic anemia, prednisolone is prescribed in a daily dose of 60-80 mg. With inefficiency, it can be increased to 150 mg or more. The daily dose of the drug is divided into 3 parts in a ratio of 3:2:1. As the hemolytic crisis subsides, the dose of prednisolone is gradually reduced (2.5-5 mg per day) to half the original. A further reduction in the dose of the drug in order to avoid recurrence of the hemolytic crisis is carried out at 2.5 mg for 4-5 days, then in smaller doses and at longer intervals until the drug is completely discontinued. In chronic autoimmune hemolytic anemia, it is enough to prescribe 20-25 mg of prednisolone, and as the general condition of the patient and erythropoiesis indicators improve, transfer to a maintenance dose (5-10 mg). With cold hemagglutinin disease, similar therapy with prednisolone is indicated.

Splenectomy for autoimmune hemolytic anemia associated with thermal agglutinins and autoerythroopsonins can only be recommended for patients in whom corticosteroid therapy is accompanied by short-term remissions (up to 6-7 months) or there is resistance to it. In patients with hemolytic anemia caused by hemolysins, splenectomy does not prevent hemolytic crises. However, they are observed less frequently than before surgery, and are easier to stop with the help of corticosteroid hormones.

With refractory autoimmune hemolytic anemia, immunosuppressants (6-mercaptopurine, imuran, chlorbutine, methotrexate, cyclophosphamide, etc.) can be used in combination with prednisolone.

In the stage of a deep hemolytic crisis, transfusions of erythrocyte mass, selected using an indirect Coombs test, are used; to reduce severe endogenous intoxication, gemodez, polydez and other detoxification agents are prescribed.

Treatment of hemolytic-uremic syndrome, which can complicate the course of autoimmune hemolytic anemia, includes corticosteroid hormones, fresh frozen plasma, plasmapheresis, hemodialysis, transfusion of washed or cryopreserved erythrocytes. Despite the use of a complex of modern therapeutic agents, the prognosis is often unfavorable.

Which Doctors Should You See If You Have Autoimmune Hemolytic Anemia

Hematologist

Promotions and special offers

medical news

14.11.2019

Experts agree that it is necessary to attract public attention to the problems of cardiovascular diseases. Some of them are rare, progressive and difficult to diagnose. These include, for example, transthyretin amyloid cardiomyopathy.

A long weekend is coming, and many Russians will go on vacation outside the city. It will not be superfluous to know how to protect yourself from tick bites. The temperature regime in May contributes to the activation of dangerous insects ...

05.04.2019

The incidence of whooping cough in the Russian Federation in 2018 (compared to 2017) almost doubled1, including in children under 14 years of age. The total number of reported cases of whooping cough in January-December increased from 5,415 cases in 2017 to 10,421 cases in the same period in 2018. The incidence of whooping cough has been steadily increasing since 2008...

Medical Articles

Almost 5% of all malignant tumors are sarcomas. They are characterized by high aggressiveness, rapid hematogenous spread and a tendency to relapse after treatment. Some sarcomas develop for years without showing anything ...

Viruses not only hover in the air, but can also get on handrails, seats and other surfaces, while maintaining their activity. Therefore, when traveling or in public places, it is advisable not only to exclude communication with other people, but also to avoid ...

Returning good vision and saying goodbye to glasses and contact lenses forever is the dream of many people. Now it can be made a reality quickly and safely. New opportunities for laser vision correction are opened by a completely non-contact Femto-LASIK technique.

Cosmetic preparations designed to care for our skin and hair may not actually be as safe as we think.

Autoimmune hemolytic anemia is caused by antibodies that react with red blood cells at 37°C (warm antibody hemolytic anemia) or

Hemolysis is usually extravascular. Direct antiglobulin test (Coombs) determines the diagnosis and may suggest the cause of hemolysis. Therapeutic measures depend on the cause of hemolysis and include the use of glucocorticoids, intravenous immunoglobulin, immunosuppressants, splenectomy, avoidance of blood transfusions and / or drug withdrawal.

ICD-10 code

D59.1 Other autoimmune hemolytic anemias

Causes of autoimmune hemolytic anemia

Warm antibody hemolytic anemia is the most common form of autoimmune hemolytic anemia (AIHA), affecting more women with this type of anemia. Autoantibodies usually react at 37°C. They can occur spontaneously or in combination with some other diseases (SLE, lymphoma, chronic lymphocytic leukemia). Certain drugs (eg, methyldopa, levodopa) stimulate the production of autoantibodies against Rh antigens (methyldopa type AIHA). Some drugs stimulate the production of autoantibodies against the erythrocyte antibiotic-membrane complex as part of a transient hapten mechanism; The hapten may be stable (eg, high dose penicillins, cephalosporins) or unstable (eg, quinidine, sulfonamides). In hemolytic anemia with warm antibodies, hemolysis occurs predominantly in the spleen, the process is often intense and can be fatal. Most autoantibodies in this type of hemolysis are IgG, a significant part are panagglutinins and have limited specificity.

Drugs that can cause hemolytic anemia with warm antibodies

Cold agglutinin disease (Cold antibody disease) is caused by autoantibodies that react at temperatures below 37°C. Sometimes occurs in infections (especially mycoplasmal pneumonia or infectious mononucleosis) and lymphoproliferative diseases; about 1/3 of all cases are idiopathic. Cold agglutinin disease is the main form of hemolytic anemia in elderly patients. Infections usually cause an acute form of the disease, while idiopathic forms tend to be chronic. Hemolysis occurs mainly in the extravascular mononuclear phagocytic system of the liver. Anemia is usually moderate (hemoglobin > 75 g/l). Antibodies in this form of anemia are represented by IgM. The degree of hemolysis is more pronounced the higher the temperature (closer to normal body temperature) at which these antibodies react with red blood cells.

Paroxysmal cold hemoglobinuria (PCH, Donath-Landsteiner syndrome) is a rare type of cold agglutinin disease. Hemolysis is provoked by cooling, which may even be localized (eg, drinking cold water, washing hands with cold water). IgG autohemolysins bind to erythrocytes at low temperature and cause intravascular hemolysis after rewarming. This occurs most often after a nonspecific viral infection or in healthy people, occurs in patients with congenital or acquired syphilis. The severity and speed of development of anemia varies and may have a fulminant course.

Symptoms of autoimmune hemolytic anemia

The symptoms of hemolytic anemia with warm antibodies are due to the presence of anemia. In severe disease, there is an increase in body temperature, chest pain, fainting, signs of heart failure. Moderately expressed splenomegaly is a typical phenomenon.

Cold agglutinin disease manifests itself in the form of acute or chronic forms. Other cryopathic symptoms may also be present (eg, acrocyanosis, Raynaud's phenomenon, cold-associated occlusive disorders). Symptoms of PNH may include severe pain in the back and lower extremities, headache, nausea, diarrhea, dark brown urine; splenomegaly may occur.

Diagnosis of autoimmune hemolytic anemia

AIHA is suspected in patients with hemolytic anemia, especially those with severe symptoms and other characteristic findings. Routine laboratory tests usually confirm the presence of extravascular hemolysis (eg, no hemosiderinuria, normal haptoglobin) unless the anemia presents suddenly and severely or is caused by PNH. Typical features are spherocytosis and high MCHC.

AIHA is diagnosed by determining autoantibodies using a direct antiglobulin test (Coombs). Anti-globulin serum is added to the patient's washed erythrocytes; the presence of agglutination indicates the presence of immunoglobulin, usually IgG, or the C3 component of complement associated with the surface of the erythrocyte. The sensitivity of the test for AIHA is about 98%. If the antibody titer is very low, or if the antibodies are IgA and IgM, false negative test results are possible. In general, the intensity of the direct antiglobulin test correlates with the number of IgG or complement C3 molecules bound to the erythrocyte membrane and roughly with the degree of hemolysis. The indirect antiglobulin test (Coombs) consists in mixing the patient's plasma with normal red blood cells to determine the presence of antibodies in the plasma. A positive indirect antiglobulin test and a negative direct test usually indicate the presence of alloantibodies due to pregnancy, prior transfusions, or lectin cross-reactivity rather than the presence of autoimmune hemolysis. It must be taken into account that the detection of warm antibodies alone does not determine the presence of hemolysis, since 1/10,000 of normal blood donors have a positive test for these antibodies.

When establishing the diagnosis of autoimmune hemolytic anemia using the Coombs test, it is necessary to make a differential diagnosis between hemolytic anemia with warm antibodies and cold agglutinin disease, as well as determine the mechanism responsible for hemolytic anemia with warm antibodies. This diagnosis can often be made with a direct antiglobulin test. There are three options:

1. the reaction is positive with anti-lgG and negative with anti-C3. This pattern is typical of idiopathic autoimmune hemolytic anemia, as well as drug- or methyldopa-type autoimmune hemolytic anemia, usually warm antibody hemolytic anemia;
2. the reaction is positive with anti-lgG and anti-C3. This pattern is typical in cases with SLE or idiopathic autoimmune hemolytic anemia with warm antibodies and less commonly in drug-associated cases;
3. the reaction is positive with anti-C3 and negative with anti-lgG. This manifests itself in idiopathic autoimmune hemolytic anemia with warm antibodies, when low-affinity IgG is present, in some drug-associated cases, in cold agglutinin disease, paroxysmal cold hemoglobinuria.

Other diagnostic studies used for autoimmune hemolytic anemia are usually inconclusive. In cold agglutinin disease, red blood cells agglutinate on blood smears, and automatic analyzers often detect elevated MCV and falsely low hemoglobin levels. After warming the hands and the subsequent recalculation of the results, the indicators change in the direction of their normalization. Differential diagnosis between warm antibody hemolytic anemia and cold agglutinin disease can be made by determining the temperature at which a direct antiglobulin test is positive. A positive test at >37°C indicates warm antibody hemolytic anemia, while a positive test at low temperature indicates Cold Agglutinin Disease.

Treatment of autoimmune hemolytic anemia

With drug-induced hemolytic anemia with warm antibodies, drug withdrawal reduces the intensity of hemolysis. In the methyldopa type of autoimmune hemolytic anemia, hemolysis usually stops within 3 weeks, but a positive Coombs test may persist for more than 1 year. In hapten-associated autoimmune hemolytic anemia, hemolysis stops after the blood plasma is cleared of the drug. The intake of glucocorticoids leads to a moderately pronounced effect in drug-induced hemolysis, lg infusions have a more significant effect.

Glucocorticoids (eg, prednisone 1 mg/kg orally twice daily) is the treatment of choice for warm-antibody idiopathic autoimmune hemolytic anemia. With very severe hemolysis, the recommended initial dose is 100 to 200 mg. Most patients have a good response to therapy, which persists in 1/3 of cases after 12-20 weeks of therapy. When stabilization of the level of erythrocytes in the blood is achieved, a slow decrease in the dose of glucocorticoids is necessary. Patients with relapse of hemolysis after discontinuation of glucocorticoids or with initial ineffectiveness of this method of treatment undergo splenectomy. After splenectomy, a good response is observed from 1/3 to 1/2 of patients. In the case of fulminant hemolysis, plasmapheresis is effective. For less severe but uncontrolled hemolysis, immunoglobulin infusions provide temporary control. Long-term immunosuppressant therapy (including cyclosporine) may be effective in relapse after glucocorticoid therapy and splenectomy.

The presence of panagglutinating antibodies in hemolytic anemia with warm antibodies makes it difficult to cross-match donor blood. In addition, transfusions often result in a summation of alloantibody and autoantibody activity, stimulating hemolysis. Therefore, blood transfusions should be avoided whenever possible. If necessary, blood transfusions should be made in small quantities (100-200 ml in 1-2 hours) under the control of hemolysis.

In acute cases of cold agglutinin disease, only supportive therapy is performed, since the course of anemia is self-limiting. In chronic cases, treatment of the underlying disease often controls the anemia. However, in chronic idiopathic variants, moderately severe anemia (hemoglobin from 90 to 100 g/l) can continue throughout life. Refrigeration must be avoided. Splenectomy does not give a positive effect. The effectiveness of immunosuppressants is limited. The use of blood transfusions requires caution; if necessary, blood transfusions should be heated in thermostatic heaters. The effectiveness of transfusions is low, since the life expectancy of allogeneic erythrocytes is much lower than that of autologous ones.

With UCH, treatment consists in severely limiting exposure to the cold. Splenectomy is ineffective. The effectiveness of immunosuppressants has been shown, but their use should be limited to cases of progression of the process or idiopathic variants. Treatment of existing syphilis can cure HCH.