Autoimmune hemolytic anemia in adults. Autoimmune hemolytic anemia: symptoms and choice of effective treatment Autoimmune hemolytic anemia: symptoms and choice of effective treatment Hemolytic anemia kris

There are idiopathic autoimmune anemias and secondary autoimmune anemias.
Secondary autoimmune hemolytic anemias develop against the background the following diseases: rheumatoid arthritis, scleroderma, Sjogren's syndrome, lymphoproliferative diseases, other malignant diseases, fungal infections, thymoma, ulcerative colitis, B12-deficiency anemia, Kawasaki disease, primary biliary cirrhosis.

In the absence of reasons for autoimmune hemolytic anemia verify idiopathic AIHA.

AIHA - hemolytic anemia resulting from changes in function immune system the body, as a result of which AT is produced against its own unchanged antigens of erythrocytes.

Etiology.
Reasons for the development of AIHA, like many others autoimmune diseases, are not clear. The impact of some trigger agent (possibly a virus or microorganism), as a result of which immunological tolerance to self-antigen is disrupted, is discussed.

Pathogenesis.
The nature of the pathogenetic mechanisms in AIHA depends mainly on the nature of AT produced against their own unchanged antigens of erythrocytes.
Red blood cells loaded with antibodies (agglutinins or precipitins) are destroyed in the spleen, liver and bone marrow, hemolysis occurs according to the intracellular type.
AT class hemolysins, when fixed on the surface of the erythrocyte, cause cell death inside the vessel.
Manifestations of the disease will be primarily determined by the mechanism of destruction of red blood cells - intracellular or intravascular.

Classification AT: by mechanism of action (agglutinins, hemolysins, precipitins); according to the temperature optimum of activity (heat, cold); according to serological characteristics (complete, incomplete).

Clinical picture.
The most common variant is AIHA, caused by incomplete heat agglutinins (anemia with intracellular death of red blood cells).
Complaints are caused by the development of tissue hypoxia (severe weakness, drowsiness, fainting, shortness of breath, palpitations).
Low-grade or febrile body temperature is often noted.
Some patients, especially the elderly, may develop anemic precoma and coma.

Patients with cardiac damage are at high risk of acute left ventricular failure.
On examination: severe pallor of the skin and visible mucous membranes. The formation of a large amount of indirect bilirubin from degrading red blood cells leads to the development of jaundice.
In 2/3 of patients, an enlargement of the spleen is detected, and in more than half of the patients, an enlargement of the liver.

With AIHA caused by the formation of the AT class of hemolysins (anemia with intravascular death of red blood cells), patients complain of pain in the lumbar region, increased body temperature, the appearance of black urine, and also have complaints associated with a decrease in the content of Hb (anemic syndrome).

The skin and visible mucous membranes are pale.
An enlarged spleen is uncommon and its size is small. Diagnostics.
The combination of anemic syndrome, jaundice of the skin and (or) mucous membranes, as well as an enlarged spleen should make the doctor first of all suspect AIHA with an intracellular mechanism of destruction of red blood cells.

This assumption requires an immediate study of peripheral blood with a mandatory determination of the number of reticulocytes.
There is a significant decrease in the content of erythrocytes and Hb in the blood. The color index is close to one, the standard deviation of erythrocytes is in the range of 80-95 fL (normocytosis).
The content of reticulocytes is significantly increased.
In severe cases, normoblasts may appear in the peripheral blood.
The number of leukocytes and platelets is within normal limits. The leukocyte formula is not changed, although leukemoid reactions of the neutrophil type can also be observed.
ESR is significantly increased. When examining urine, the appearance of urobilin may be detected.

Feces in patients with AIHA with an intracellular mechanism of destruction of red blood cells acquire a darker color than usual.

To verify the diagnosis AIHA with an intracellular mechanism of destruction of erythrocytes uses a test that determines the presence of AT on the surface of erythrocytes - a positive direct Coombs test (Coombs test: rabbit antiglobulin serum, obtained by sensitizing it with human γ-globulin, is added to the erythrocytes being tested.
The serum does not cause agglutination of normal washed erythrocytes, but when antiglobulin serum is added to erythrocytes containing incomplete AT on their surface, the protein molecules become larger and the erythrocytes agglutinate).
A more sensitive test is the hemagglutination aggregation reaction.
If a patient develops black urine, pain in the lumbar region and anemic complaints, it is necessary to assume the presence of AIHA with intravascular destruction of red blood cells.

This assumption is strengthened when normochromic (normocytic) anemia is detected with an increase in the number of reticulocytes.
When examining urine, free hemoglobin is detected, and when examining urinary sediment, an increase in the number of renal tubular epithelial cells with inclusions of hemosiderin is noted.
Pathomorphology of the bone marrow: hyperplasia of the red line of hematopoiesis of varying severity.
In severe hemolytic crises bone marrow is able to increase the production of red blood cells by 6-8 times.

Differential diagnosis.
AIHA with an intracellular mechanism of destruction of red blood cells must be differentiated from other anemic conditions accompanied by an increase in the number of reticulocytes: posthemorrhagic anemia; IDA during therapy with iron supplements; B12DA during vitamin B12 therapy; FDA during therapy folic acid.

To distinguish between these conditions, a careful study of the medical history and analysis of available documentary data on the course of the disease are of great importance. An important help is the Coombs test; AIHA with intravascular destruction of erythrocytes must be differentiated from PNH (negative sucrose test and Hem's test in AIHA and positive in PNH).

Treatment.
AIHA requires immediate treatment.
First-line drugs - GCS - prednisolone orally at a dose of 1-2 mg/kg body weight per day.
Signs of the effectiveness of treatment are the cessation of the decrease in Hb, a decrease in reticulocytosis, normalization of body temperature, and improvement in the patient’s well-being.

Hemoglobin begins to increase on the 3-4th day from the start of treatment.
After normalization of peripheral blood parameters, the dose of prednisolone begins to be slowly reduced until completely discontinued.
The recommended dose of prednisolone for patients over 70 years of age with signs of osteoporosis is 0.6 mg/kg body weight/day.
If, due to some circumstances, the patient cannot receive GCS orally, then when administered parenterally, their dose must be increased.
If prednisolone is administered intramuscularly, its dose should be doubled, and if administered intravenously, it should be tripled compared to the dose received orally.

It should also be taken into account that when administered parenterally, prednisolone has a short-term effect.
The use of GCS therapy allows obtaining a lasting effect in half of the patients.
For others, treatment with prednisolone provides a temporary effect; dose reduction or complete withdrawal of the drug leads to the development of relapse of the disease.

Such patients require constant administration of a maintenance dose of prednisolone or repeated courses of therapy.

Splenectomy as second line therapy is indicated in following cases:
1) no effect on prednisolone;
2) dependence on prednisolone at a dose of 20 mg/day or more;
3) early relapse after discontinuation of prednisolone.

In AIHA with intravascular death of red blood cells, the effect of splenectomy is less and may be delayed.

The therapeutic effect in this case is associated with the exclusion of the spleen from the process of AT synthesis.

For patients over 70 years of age and children, splenectomy is not second-line therapy due to the high risk of immunodeficiency and infectious complications.

Third line therapy.
If splenectomy is ineffective, immunosuppressants are prescribed.
IN recent years A good effect was obtained in the treatment of AITA with cyclosporine A (sandimmune).
The initial dose is 2.5 mg/kg x 2 times a day for 6 days, followed by a reduction in the dose of cyclosporine to 3 mg/kg per day and the addition of 5 mg/day prednisolone.

The use of cyclosporine A allows one to obtain long-term and stable remissions of the disease.

Mycophenolate has also been shown to be effective in the treatment of AIHA.
Rituximab (MabThera) 375 mg/m2 once a week - for 4 weeks. Some researchers show a 100% response rate.

Imuran (azathiolrine - 1.5 mg/kg/day for 3 months) or low doses of cyclophosphamide (2 mg/kg/day x 3 months). Response is observed in 50% of patients.

High doses cyclophosphamide (50 mg/kg per day x 4 days) induced long-term remissions (15 months) in 66% of patients.

Forecast.
With adequate therapeutic management tactics, the prognosis for patients with AIHA is favorable.

Prevention. There is no effective prevention for AIHA.

The type of hemolysis is usually extravascular. Direct antiglobulin bodies (Coombs test) allows you to establish a diagnosis and suggest the cause. Treatment depends on the cause and may include the use of corticosteroids, intravenous immunoglobulins, immunosuppressants, splenectomy, avoidance of blood transfusions, and withdrawal of certain medications.

Causes of autoimmune hemolytic anemia

Hemolysis occurs mainly in the spleen. It often becomes severe and can be fatal. Most warm autoantibodies are IgG. They are panagglutinins and are most often characterized by limited specificity.

Cold agglutinin disease is caused by autoantibodies that react at temperature<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 classified as IgM.

Paroxysmal cold hemoglobinuria is 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, and a 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 as acute or chronic hemolytic anemia. Other manifestations of increased cold sensitivity may be present (acrocyanosis, Raynaud's phenomenon, cold-associated occlusive lesions). Hepatosplenomegaly may be present.

Diagnosis of autoimmune hemolytic anemia

• Range of studies to identify hemolytic anemia.
• Direct antiglobulin test.

AIHA should be suspected in patients with hemolytic anemia, especially if it is severe or other characteristic symptoms. The results of routine laboratory tests indicate the presence of extravascular hemolysis (no hemosiderinuria; haptoglobin levels are close to normal), except in cases of severe acute course or symptoms caused by UCG. The presence of spherocytosis and increased MSHC are typical.

Diagnosis of AIHA is based on an antiglobulin test. Antiglobulin serum is added to the patient's washed red blood cells; agglutination indicates the presence of immunoglobulins or complement (C) associated with red blood cells. 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 SZ. 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.

Once the diagnosis of AIHA is made using the Coombs test, further examination is necessary.

There are three options:

• The reaction is positive for anti-IgG and negative for anti-SZ. This variant occurs in idiopathic and drug-induced (in response to the use of α-methyldopa) AIHA, and it is also usually characteristic of hemolytic anemia caused by 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 variant is observed in 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 HCG.

There are other studies that suggest the cause of AIHA, but they are not diagnostically significant. In cold agglutinin disease, red blood cells are located in the peripheral blood smear in the form of clusters. Related to this is that automatic cell counting often reveals an increase in MCV and an apparent decrease in hemoglobin levels; When heating the vessel with your hands and then counting the indicators, they are observed to significantly approach the norm.

Treatment of autoimmune hemolytic anemia

Corticosteroids are the treatment of choice for idiopathic AIHA caused by warm antibodies. For extremely severe hemolysis, an introductory dose of 100-200 mg is recommended. When the number of red blood cells stabilizes, corticosteroids are gradually withdrawn. If corticosteroid therapy is ineffective or a relapse occurs after its 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. For less severe but uncontrolled hemolysis, immunoglobulin infusions may provide temporary improvement. 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, control of anemia is often achieved by treating the underlying disease. However, in idiopathic chronic disease, mild anemia (Hb 9-10 g/dL) may persist throughout life. Avoiding exposure to cold also leads to significant improvement. Splenectomy is ineffective. The effectiveness of immunosuppressants is moderate. Blood transfusions should be performed carefully, with pre-warming of the blood. Because autologous red blood cells are already resistant to autoantibodies, they have a longer lifespan than donor cells, limiting the effectiveness of blood transfusion.

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

Hemolytic anemia is a disease characterized by the destruction of red blood cells. It shortens the lifespan of red blood cells. Normally they last about 120 days.

Every day, about 1% of red cells are removed from the blood. The number of dead red blood cells increases due to hemolysis (destruction). Because of this, hypoxia of brain tissue and internal organs is formed.

Physiologically, instead of dead cells, young red blood cells and depots are released from the red bone marrow into the blood. This is how “rejuvenation” of the blood occurs. In hemolytic conditions (autoimmune, B12 deficiency) this process is disrupted.

The intense destruction of red blood cells is not balanced by the formation of young forms. A blood test in this situation shows reticulocytosis (increased number of immature red blood cells).

The presence of reticulocytosis in laboratory tests confirms the diagnosis of hemolytic anemia. Even against the background of a normal blood hemoglobin concentration, the appearance of reticulocytes indicates the presence of hemolysis.

Autoimmune hemolytic anemia - what is it?

To answer the question, we will describe the pathogenesis of the disease.

The first sign of the disease is aplastic (aregenerative) crisis. It causes bone marrow failure. Against the background of pathology, irritation of the erythroid red sprout occurs. Regenerative hemolytic anemia (aplastic) is accompanied by a decrease in the number of reticulocytes, so the interpretation of the blood test does not show specific changes.

If the initial stage of the disease is missed, severe hemolytic anemia occurs. Patients know that severe hemolysis is a condition in which severe weakness occurs that does not allow normal physical activity. During crises, a person may lose consciousness.

Autoimmune hemolytic anemia is the destruction of red blood cells that occurs due to damage to the erythroid series by antibodies of the immune system. The cause of this disease is unknown. Clinical experiments have shown a significant influence on the occurrence of pathology of hereditary factors.

Hemolysis - what is it?

Hemolysis is a condition that is combined with compensatory hyperplasia of the erythroid lineage. Against this background, a decrease in the number of blood reticulocytes is formed. With a long course of the disease, a severe and threatening form of pathology occurs. A reduction in the lifespan of red blood cells against this background leads to dangerous conditions and serious complications.

Various pathological processes that occur 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 as “enemy” and begins to fight against them. Autoimmune hemolytic anemia belongs to a group of rare diseases in which the formation of antibodies to one’s own red blood cells is observed. The consequences of this phenomenon are quite serious, since disturbances in the circulatory system affect the functioning of the entire body.

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

Acquired autoimmune hemolytic anemias are classified according to the factor that triggered the progression of the disease. In the case where it is not possible to associate the formation of a provoking factor resulting in the rejection of red blood cells, 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 progressing painful sensations.
2. Shortness of breath even with minor exertion.
3. Painful discomfort in the heart area.
4. There is an increase in body temperature and vomiting.
5. The appearance of yellowness of the skin.

The chronic form is outwardly manifested by the patient’s relatively satisfied condition, even if the disease has long been advanced. Yellowness of the skin often appears; ultrasound reveals an enlarged spleen. Periods of exacerbation alternate with a calm course of the disease. The ICD 10 reference code for autoimmune hemolytic anemia stands for D59.

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

Autoimmune hemolytic anemia in children

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

Diagnostics

Clinical and hematological signs provide the basis for a diagnosis of autoimmune hemolytic anemia. Also for diagnosis, a Coombs test is performed, which reliably reflects the patient’s condition. The blood picture determines the presence of microspherocytes, normoblasts, and normochromic anemia. The ESR level is often significantly elevated, as well as the level of bilirubin in the blood.

Treatment of autoimmune hemolytic anemia

To treat autoimmune anemia, you must consult 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 treatment activities are carried out for almost three months. A negative Coombs test is considered a productive result. Only after this does treatment stop. In some cases, autoimmune anemic pathology cannot be treated. Then only surgical intervention is prescribed - removal of the spleen.

In acute cases of the disease, a blood transfusion may be required. Prednisolone is also prescribed for cold or chronic anemia. The disease is quite difficult to treat. Despite all modern therapeutic therapies, the prognosis for autoimmune anemia is often unfavorable.

Prevention

It is not possible to prevent or predict the occurrence of such a disease, and therefore there are no practical preventive methods. It is worth adding that the most effective and efficient way to prevent any diseases is a healthy lifestyle.