Warm Autoimmune Hemolytic Anemias

• Autoimmune hemolytic anemias (AIHAs) are caused by the body producing antibodies against its own red blood cells.
• AIHAs are divided into warm and cold types, based on whether the antibody reacts more strongly with red cells at 37°C or 4°C.

Warm Autoimmune Hemolytic Anemias

• Red cells are coated with immunoglobulin (Ig) and taken up by RE macrophages, which have receptors for the Ig Fc fragment.
• The cell loses part of its coated membrane and becomes more spherical to maintain its volume.
• Premature destruction occurs predominantly in the spleen.
• Red cell destruction happens more generally in the RE system when cells are coated with IgG and complement (C3d) or complement alone.

Clinical Features of Warm AIHA

• The disease can occur at any age and in either sex.
• It presents as hemolytic anemia of varying severity.
• The spleen is often enlarged.
• The disease tends to remit and relapse.
• It can occur alone or with other diseases.
• When associated with idiopathic thrombocytopenic purpura (ITP), it is referred to as Evans syndrome.
• When secondary to systemic lupus erythematosus, the cells are typically coated with immunoglobulin and complement.

Lab Findings for Warm AIHA

• Hematological and biochemical findings are typical of extravascular hemolytic anemia, with spherocytosis prominent in the peripheral blood.
• The DAT (Direct Antiglobulin Test) is positive due to IgG, IgG, and complement, or IgA on the cells.
• In some cases, the autoantibody shows specificity within the Rh system.
• Antibodies on the cell surface and free antibodies in serum are best detected at 37°C.

Treatment for Warm AIHA

• Remove any underlying cause, if present.
• Corticosteroids such as Prednisolone are the usual first-line treatment, 60 mg/day is a typical starting dose in adults and should then be tapered down.
• Patients with predominantly IgG on red cells respond better, whereas those with complement often respond poorly to corticosteroids and splenectomy.
• Immunosuppression may be tried if steroids and/or splenectomy have failed, using drugs or monoclonal antibodies.
• Anti-CD20 monoclonal antibodies have produced prolonged remissions in some cases.
• High-dose immunoglobulin has been used but with less success than in ITP.
• Treating the underlying disease, e.g., chronic lymphocytic leukemia or lymphoma, may be necessary.
• Folic acid is given in severe cases.
• Blood transfusion may be needed if anemia is severe and causing symptoms.
• The least incompatible blood should be used, and if the autoantibody specificity is known, donor blood lacking the relevant antigen(s) should be chosen.
• Patients can readily make alloantibodies against donor red cells.

Cold Autoimmune Hemolytic Anemias

• In these syndromes, the autoantibody can be monoclonal, as in idiopathic cold hemagglutinin syndrome, or associated with lymphoproliferative disorders.
• The autoantibody can also be polyclonal following infection, e.g., infectious mononucleosis or Mycoplasma pneumonia.
• The antibody attaches to red cells mainly in the peripheral circulation where blood temperature is cooler.
• The antibody is usually IgM and binds best to red cells at 4°C.
• IgM antibodies are highly efficient at fixing complement, and both intravascular and extravascular hemolysis can occur.
• Often, only complement is detected on the red cells, as the antibody elutes off in warmer parts of the circulation.
• The antibody in nearly all cold AIHA syndromes is directed against the "I" antigen on the red cell surface.

Clinical Features of Cold AIHA

• Patients may have chronic anemia aggravated by cold, associated with intravascular hemolysis.
• Mild jaundice and splenomegaly may be present.
• Acrocyanosis (purplish skin discoloration) may develop at the tips of the nose, ears, fingers, and toes due to red cell agglutination in small vessels.

Lab Findings for Cold AIHA

• Similar to warm AIHA, but spherocytosis is less marked. Red cells agglutinate in the cold
• DAT reveals complement (C3d) only on the red cell surface.
• The serum shows a high titre of "cold" autoantibodies to red cells.

Treatment of Cold AIHA

• Consists of keeping the patient warm and treating the underlying cause, if present.
• Anti-CD20, and anti-CD52 have been used; Rituximab is effective when there is an associated B-lymphoproliferative disease.
• Splenectomy is usually not helpful unless massive splenomegaly is present.

Warm autoimmune hemolytic anemias (AIHAs) involve the body producing antibodies against its own red blood cells. Red cells are coated with immunoglobulin and taken up by macrophages, leading to premature destruction predominantly in the spleen. The disease presents as hemolytic anemia of varying severity and can occur at any age.