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Autoimmune Hemolytic Anemia

Hemolysis in autoimmune hemolytic anemia (AIHA) is affected by IgG or IgM (rarely IgA) antibodies. In general, IgG antibodies react with their antigen at body temperature and IgM antibodies react best at lower temperatures; the exceptions to this rule are the cold-reacting IgG antibodies of paroxysmal cold hemoglobinuria.

Therapy in AIHA centers around three objectives: (1) reduction in the production of antibody; (2) reduction in the amount of available antibody; or (3) diminution in the means of destruction due to antibody or complement. The means by which these objectives are obtained.

IgG antibody is produced by clones of cells that have undergone isotype rearrangement and are potentially under the control of the T cell helper-suppressor system. Autoimmune antibodies presumably emerge when that control is faulty and self-recognizing antibodies are either insufficiently suppressed or are stimulated.

The "traditional" ways of suppressing production of autoimmune IgG antibodies include the use of glucocorticoids (particularly prednisone) and cytotoxic chemotherapeutic drugs. Prednisone may have a specific effect on the T cells regulating the expression of antigen-specific clones as it has been shown that the simultaneous presence of Glucocorticoids in their receptor and antigen in its receptor initiates apoptosis. Cyclosporin A regulates T cell expression

Drug-related antibody

Drug-related antibodies can be divided into two categories: those in which the drug forms part of the antigen and those in which it does not. When the drug is a major component of the antigen, stopping the drug is usually enough to assure the cessation of the hemolysis.

Some drugs appear to alter the immune system, causing immune hemolytic anemia that is frequently severe. Patients with chronic lymphocytic leukemia treated with fludarabine or pentostatin may exhibit this. The reaction has been reported with treatment with tacrolimus and a interferon.

Cold-reacting IgG (Donath-Landsteiner) antibody

Paroxysmal cold hemoglobinuria (PCH) is caused by a cold-reacting IgG antibody and is difficult both to diagnose and to treat. The traditional bithermic Donath-Landsteiner reaction is insensitive, but its sensitivity can be markedly increased by the use of the cells of patients.

IgM antibodies are the product of clones that have not undergone isotype rearrangement and are therefore not in the memory repertoire under the control of the T cell system. Thus, when they are stimulated by viral or mycoplasmal infections, they disappear when the infection regresses and treatment is usually not necessary. More commonly, they are due to paraneoplastic.

Warm-reacting IgM and mixed antibodies

Warm-reacting IgM antibodies occurring alone are rare but may cause particularly severe hemolytic anemia. Destruction is due to complement and virtually the only therapeutic option available is chemotherapy. The incidence is so rare that few data are available.

Uncommonly (about 5% of the time), both IgG and IgM antibodies are present. The IgM antibodies may react up to 37EC. When they do so, hemolysis may be severe.

Transfusion in autoimmune hemolytic anemia

Transfusion may be necessary in the treatment of AIHA but is complicated by the presence of antibodies in the patient's serum, making compatibility testing difficult. Transfusion danger arises not from the autoantibodies that are present but from any alloantibodies that may have been stimulated by previous transfusion or pregnancy. Cold agglutinins can be bypassed by performing all reactions at 37EC and testing in the antiglobulin phase with anti-IgG.