Autoimmune hemolytic anemia with complete cold agglutinins

Autoimmune hemolytic anemia with complete cold agglutinin disease (cold agglutinin disease) in children is much less common than other forms. In adults, this disease is often found: this form is either secondary to lymphoproliferative syndromes, hepatitis C, infectious mononucleosis, or idiopathic. In the idiopathic form of anemia, however, the presence of clonal expansion of a population of morphologically normal lymphocytes producing monoclonal IgM is also shown. In the overwhelming majority of cases, the antibodies are directed against the carbohydrate determinants of the I / i complex of the erythrocyte surface. In 90% of cases, antibodies are specific for I, and in 10% antibodies against i are formed. Despite the fact that in this form of autoimmune hemolytic anemia, antibodies react with erythrocytes at low temperature and bind complement, manifest intravascular thrombosis is a rarity, and the clearance of "sensitized" erythrocytes is mediated by the C3c receptors of the liver macrophages and to a lesser extent by the spleen. Provocation of the hemolytic crisis often serves as hypothermia: on walks in cold weather and in the wind, during bathing, etc. Hemolysis in patients with cold agglutinins is often subacute, without catastrophic drop in hemoglobin concentration. The Coombs test with this form is negative in the reaction with anti-IgG, but positive in the reaction with anti-C3. Typical bright spontaneous agglutination of erythrocytes on the glass. Treatment with glucocorticosteroids, cyclophosphamide and interferon, as well as splenectomy are not effective for autoimmune hemolytic anemia with complete Cold agglutinins, and complete remissions are rare. In this regard, there is a need to search for and introduce new methods of medicament, primarily immunosuppressive treatment of autoimmune hemolytic anemia.

Treatment with rituximab (monoclonal antibodies to the CD20 molecule), already used for several years in the treatment of oncohematological and autoimmune diseases, has become yet another effective method of conservative treatment of autoimmune hemolytic anemia, although the question of its place is not finally solved. Naturally, while rituximab is not considered a drug of the first line of therapy, however in subsequent lines its place is obvious. On the other hand, good efficacy of rituximab in the case of Cold agglutinin, usually resistant to standard immunosuppressive therapy, may soon put it in the first line. Indications for rituximab in autoimmune hemolytic anemia:

• autoimmune hemolytic anemia caused by thermal or cold antibodies;
• Fisher-Evans syndrome:
  • when refractory to first therapy (glucocorticosteroids) and the second (splenectomy, cyclophosphamide, high doses of immunoglobulins) line;
  • with a dependence on high doses of glucocorticosteroids (> 0.5 mg / kg per day).

The usual course of rituximab therapy consists of 4 injections in a single dose of 375 mg / m ² at a weekly interval. According to available data, 50-80% of patients with autoimmune hemolytic anemia respond to rituximab. As a rule, in parallel with the treatment with rituximab, it is recommended to use glucocorticosteroids in the previous dose, if it is not more than 1 mg / kg per day. Other immunosuppressive therapy (eg, azathioprine, cyclosporine) is recommended to be canceled. However, with catastrophic hemolysis, which directly threatens the patient's life, it is possible to combine rituximab with any other therapies (ultra-high doses of glucocorticosteroids, cyclophosphamide, high doses of immunoglobulin IV). Typically, a decrease in the rate of hemolysis and the onset of an increase in hemoglobin levels occurs with the 2-3 nd week of therapy, but the quality of the response can vary significantly - from the complete cessation of hemolysis to its more or less complete compensation. Respondents consider patients who do not need hemotransfusions and have increased the level of Hb by at least 15 g / l. Approximately 25% of patients after remission come relapse, usually within the first year, with a high probability of a second response to rituximab. There are cases when patients successfully received 3 or even 4 courses of rituximab.

Transfusion therapy for autoimmune hemolysis

Indications for transfusion of erythrocyte mass depend not on the level of Hb at the moment, but on the clinical tolerability of anemia and on the rate of decrease in the hemoglobin content. Each transfusion can cause intravascular hemolysis, but the rejection of transfusion can lead to the death of the patient. It must be remembered: the more massive the transfusion, the more massive the hemolysis, so the goal of transfusion for autoimmune hemolytic anemia is not the normalization of hemoglobin concentration, but maintenance at a clinically sufficient level. The minimal typing of blood for transfusions for autoimmune hemolytic anemia includes:

• definition of ABO-affiliation;
• determination of the complete Rh phenotype (D, Cc, Ee);
• typing on Kell's antigens and the Duffy system.

Transfusions of erythrocyte mass in autoimmune hemolytic anemias are associated with certain difficulties. First, all blood samples of one group agglutinate, respectively, according to the classical canons, are incompatible. Secondly, in clinics it is impossible to differentiate alloantibodies, developed as a result of previous blood transfusions and capable of causing severe intravascular hemolysis, from autoantibodies that cause intracellular hemolysis. That is why it is recommended to treat transfusions as conservatively as possible. For the prevention of febrile nonhemolytic reactions, leukofiltration of the erythrocyte mass is recommended by filters of III-IV generations or, in extreme cases, its washing. Washing the erythrocyte mass does not weaken hemolysis and does not reduce the risk of alloantibodies formation.

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