Types of immune hemolytic anemia

Depending on the nature of the antibodies, 4 variants of immune hemolytic anemia are distinguished: alloimmune (isoimmune), transimmune, heteroimmune (hapten), autoimmune.

Isoimmune hemolytic anemia

They are noted in cases of antigenic incompatibility of the maternal and fetal genes (hemolytic disease of newborns) or in the case of incompatible erythrocytes (grouping of incompatible blood) that lead to the reaction of the donor serum with the recipient's erythrocytes.

Hemolytic disease of newborns is most often associated with maternal and fetal blood incompatibility with RhD antigen, less often with antigens A B O, even more rarely with C, Kell and others antigens. Antibodies that penetrate the placenta are fixed on the erythrocytes of the fetus and then eliminated by macrophages. Intracellular hemolysis develops with the formation of indirect bilirubin, toxic for the central nervous system, with compensatory erythroblastosis, 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 and more, no less than 15% of the first births of Rh-negative mothers. The frequency of hemolytic disease of newborns increases with obstetric interventions and placental pathology. Repeated delivery, especially with a short interval between the immunizing and the next pregnancy, as well as previous abortions with relatively long terms (10-14 weeks) increase the likelihood of sensitization and, consequently, the development of hemolytic disease. The protective effect against Rh-conflict is due to the incompatibility of 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.

The measures of prophylaxis of Rhesus sensitization include the determination of antiresusive antibodies in a sensitized woman in the dynamics of pregnancy at the 20th, 28th and 36th weeks and during childbirth. This is necessary to address the issue of the prophylactic administration of antiresus immunoglobulin - anti-D IgG - after childbirth. In cases of risk of intrauterine fetal damage (an antibody titer of more than 1: 8 in the indirect Coombs sample), amniocentesis is indicated with the determination of bilirubin content and subsequent choice of tactics of management. Effective is the administration of a female sensitized anti-D IgG at the 28th-36th week of pregnancy.

The most promising is the prophylactic administration of anti-D IgG at a dose of 200-500 mcg in the first 36-72 h after delivery. In this case, suppression of the production of specific antibodies is observed in the course of repeated pregnancy, a decrease in the frequency of hemolytic disease of newborns by more than 10 %. Indication for the introduction of immunoglobulin is the birth of a Rh-negative primipara female Rh-positive child, compatible with the mother's blood system AB0.

Transmissible hemolytic anemia

It is caused by transplacental transmission of antibodies from mothers suffering from autoimmune hemolytic anemia; antibodies are directed against the general antigen of erythrocytes both of the mother and the child. Transimmune hemolytic anemia in newborns requires systematic treatment, taking into account the half-life of maternal antibodies (IgG) in 28 days. The use of glucocorticoids is not shown.

Heteroimmune hemolytic anemia

It is associated with the fixation on the surface of the erythrocyte of a hapten of medicinal, viral, bacterial origin. Erythrocyte is a random target cell on which a hapten-antibody reaction occurs (the body produces antibodies against "foreign" antigens). In 20% of cases with immune hemolysis, the role of drugs can be revealed. A number of drugs, such as penicillin and cephalosporins, attach to the erythrocyte membrane, changing its antigenic properties, which leads to the production of antibodies directed against the erythrocyte-drug complex. Other drugs, such as phenacetin, sulfonamides, tetracycline, PASK, isoniazid, hydrochlorothiazide, quinine and quinidine, form triple immune complexes (Fab fragment of IgG - the preparation - the protein of the erythrocyte membrane), which cause destruction of the erythrocyte. Antibody and drug form immune complexes that bind non-specifically to the proteins of the erythrocyte membrane, and activate complement. The antibody is directed both against the drug and against the membrane protein. Alpha-methyldopa, levodopa, procainamide, ibuprofen, diclofenac, thioridisin, a-interferon cause the formation of antibodies directed against the membrane of erythrocyte 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 observed only in 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 anemia is similar in clinical picture to autoimmune hemolytic anemia with incomplete thermal agglutinins. The prognosis is favorable, the therapeutic effect is achieved by eliminating the hapten, for example, by canceling the medication, by sanitizing the infection. The use of glucocorticoids is possible and is due to the severity of anemia. Hemotransfusion therapy is not indicated in connection with the severity of isoimmunization.

Autoimmune hemolytic anemia

With this variant of hemolytic anemia in the patient's body, antibodies directed against their own unchanged erythrocyte antigens are produced. There are at any age.

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

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 can not be established, they speak of idiopathic autoimmune hemolytic anemia.

Autoimmune hemolytic anemia is classified according to the characteristics of the autoantibodies that mediate them: the temperature at which the antibodies react with red blood cells, and the ability to cause their agglutination and hemolysis. Thermal called antibodies that connect erythrocytes at a temperature of 36 ° C, cold - reacting with erythrocytes at a temperature of no more than 26 ° C. Antibodies, binding to the erythrocytes in the cold, and causing hemolysis in the warmth, are called biphasic. If the antibodies are only able to agglutinate the red blood cells, they are called agglutinins (complete or incomplete), if they activate complement and cause intravascular hemolysis, then we are talking about hemolysins.

According to the indicated signs, the following types of autoimmune hemolytic anemia are distinguished:

• with incomplete thermal agglutinins;
• paroxysmal cold hemoglobinuria (autoimmune hemolytic anemia with two-phase hemolysins of Donat-Landsteiner);
• with full cold agglutinins.

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

On the etiology of autoimmune hemolytic anemia may be idiopathic or secondary to infections, immunodeficiency syndromes, autoimmune diseases, lymphoproliferative syndromes [chronic lymphocytic leukemia (CLL), lymphomas], tumors, exposure to medicines.

[1], [2], [3], [4], [5], [6], [7]