Types of immune hemolytic anemias

Depending on the nature of the antibodies, there are 4 types of immune hemolytic anemia: alloimmune (isoimmune), transimmune, heteroimmune (haptenic), and autoimmune.

Isoimmune hemolytic anemias

They are observed in cases of antigenic incompatibility of the genes of the mother and fetus (hemolytic disease of the newborn) or when erythrocytes incompatible in terms of group antigens enter the body (transfusion of incompatible blood), which leads to a reaction of the donor's serum with the recipient's erythrocytes.

Hemolytic disease of the newborn is most often associated with incompatibility of the mother's and fetus's blood by the RhD antigen, less often by the A B O antigens, and even less often by the C, C, Kell and other antigens. Antibodies penetrating the placenta are fixed on the fetus's erythrocytes and then eliminated by macrophages. Intracellular hemolysis develops with the formation of indirect bilirubin, toxic to the central nervous system, with compensatory erythroblastosis, and the formation of extramedullary foci of hematopoiesis.

Immunization of the mother occurs as a result of bleeding from the mother to the fetus in a volume of 0.25 ml or more, in at least 15% of cases of the first birth in Rh-negative mothers. The frequency of hemolytic disease of the newborn increases with obstetric interventions and placental pathology. Repeated births, especially with a short interval between the immunizing and the next pregnancy, as well as previous abortions at relatively long terms (10-14 weeks) increase the likelihood of sensitization and, consequently, the development of hemolytic disease. A protective effect in relation to the Rh conflict is provided by the incompatibility of the blood of the mother and fetus in the ABO system due to the destruction of fetal cells by maternal antibodies to A- and B-antigens.

Measures for preventing Rh sensitization include determining anti-Rh antibodies in a sensitized woman during pregnancy at 20, 28, and 36 weeks and during labor. This is necessary to decide on the prophylactic administration of anti-Rh immunoglobulin - anti-D IgG - after labor. In cases of risk of intrauterine fetal damage (antibody titer over 1:8 in the indirect Coombs test), amniocentesis with determination of bilirubin content and subsequent selection of management tactics is indicated. The administration of anti-D IgG to a sensitized woman at 28-36 weeks of pregnancy is effective.

The most promising is the prophylactic administration of anti-D IgG at a dose of 200-500 mcg in the first 36-72 hours after delivery. In this case, suppression of the production of specific antibodies is observed during repeated pregnancy, a decrease in the incidence of hemolytic disease of the newborn by more than 10%. An indication for the administration of immunoglobulin is the birth of a Rh-positive child in a Rh-negative primiparous woman, compatible with the mother's blood according to the ABO system.

Transimmune hemolytic anemia

Caused by transplacental transfer of antibodies from mothers suffering from autoimmune hemolytic anemias; antibodies are directed against a common red blood cell antigen of both mother and child. Transimmune hemolytic anemia in newborns requires systematic treatment, taking into account the half-life of maternal antibodies (IgG) of 28 days. The use of glucocorticoids is not indicated.

Heteroimmune hemolytic anemia

Associated with fixation of a hapten of medicinal, viral, or bacterial origin on the surface of an erythrocyte. An erythrocyte is a random target cell on which a hapten-antibody reaction occurs (the body produces antibodies against "foreign" antigens). In 20% of cases of immune hemolysis, the role of drugs can be revealed. A number of drugs, such as penicillin and cephalosporins, attach to the erythrocyte membrane, thereby changing its antigenic properties, which leads to the production of antibodies directed against the erythrocyte-drug complex. Other drugs, such as phenacetin, sulfonamides, tetracycline, PAS, isoniazid, hydrochlorothiazide, quinine, and quinidine, form triple immune complexes (Fab fragment of IgG - drug - erythrocyte membrane protein), causing destruction of the erythrocyte. The antibody and drug form immune complexes that bind non-specifically to erythrocyte membrane proteins and activate complement. The antibody is directed against both the drug and the membrane protein. Alpha-methyldopa, levodopa, procainamide, ibuprofen, diclofenac, thioridizine, and a-interferon cause the formation of antibodies directed against the erythrocyte membrane proteins, and not against the drug. It has been established that a positive direct Coombs test is observed in 10-20% of patients receiving alpha-methyldopa, but hemolysis is noted in only 2-5%. Cephalothin causes non-specific binding of plasma proteins (including IgG, complement proteins, transferrin, albumin, and fibrinogen) to the erythrocyte membrane. The Coombs test is positive, but hemolysis is rare.

Heteroimmune hemolytic anemias are similar in clinical presentation to autoimmune hemolytic anemias with incomplete warm agglutinins. The prognosis is favorable, the therapeutic effect is achieved by eliminating the hapten, for example, by discontinuing the drug, or by cleaning up the infection. The use of glucocorticoids is possible and is determined by the severity of the anemia. Hemotransfusion therapy is not indicated due to the severity of isoimmunization.

Autoimmune hemolytic anemias

In this type of hemolytic anemia, the patient's body produces antibodies directed against its own unmodified red blood cell antigens. They occur at any age.

Depending on the cellular orientation of the antibodies, autoimmune hemolytic anemia with antibodies to the antigen of bone marrow erythrocytes and autoimmune hemolytic anemia with antibodies to the antigen of peripheral blood erythrocytes are distinguished.

Autoimmune hemolytic anemia accompanying the main pathological process - lymphoproliferative diseases (chronic lymphocytic leukemia, lymphoma), systemic connective tissue diseases (systemic lupus erythematosus, antiphospholipid syndrome) or immunodeficiency states, are considered secondary or symptomatic. If the cause of autoimmune hemolytic anemia cannot be determined, they speak of idiopathic autoimmune hemolytic anemia.

Autoimmune hemolytic anemias are classified depending on the characteristics of the autoantibodies that mediate them: the temperature at which the antibodies react with erythrocytes and the ability to cause their agglutination and hemolysis. Antibodies that bind erythrocytes at a temperature of 36 °C are called warm antibodies, while those that react with erythrocytes at a temperature of no more than 26 °C are called cold antibodies. Antibodies that bind to erythrocytes in the cold and cause hemolysis in the heat are called biphasic. If antibodies are only able to agglutinate erythrocytes, they are called agglutinins (complete or incomplete), and if they activate complement and cause intravascular hemolysis, they are hemolysins.

According to the above-mentioned signs, the following types of autoimmune hemolytic anemia are distinguished:

• with incomplete heat agglutinins;
• paroxysmal cold hemoglobinuria (autoimmune hemolytic anemia with biphasic Donath-Landsteiner hemolysins);
• with complete cold agglutinins.

Rarely, warm agglutinins may be complete and belong to the IgM class. Cases of combined autoimmune hemolytic anemias with warm and cold antibodies have also been described, in particular after infectious mononucleosis, when the Epstein-Barr virus activates a huge pool of B lymphocytes producing a wide range of antibodies.

According to etiology, autoimmune hemolytic anemias can be idiopathic or secondary to infections, immunodeficiency syndromes, autoimmune diseases, lymphoproliferative syndromes [chronic lymphocytic leukemia (CLL), lymphomas], tumors, and drug exposure.

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