Warm autoimmune hemolytic anemia

Warm Antibody Autoimmune Hemolytic Anemia (AIHA) is the most common of the autoimmune hemolytic diseases. About half of the cases are idiopathic, with the other half attributable to a predisposing condition or medications being taken.

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Pathophysiology

The most common antibody involved in warm antibody AIHA is IgG, though sometimes IgA is found. The IgG antibodies attach to a red blood cell, leaving their F_C portion sticking out. The F_C region is recognized and grabbed onto by F_C receptors found on monocytes and macrophages in the spleen. These cells will pick off portions of the red cell membrane, almost like they are taking a bite. The loss of membrane causes the red blood cells to become spherocytes. Spherocytes are not as flexible as normal RBCs, and will be singled-out for destruction in the red pulp of the spleen as well as other portions of the reticuloendothelial system. The red blood cells trapped in the spleen cause the spleen to enlarge, leading to the splenomegaly often seen in these patients.

The cause of the autoantibody formation is unknown, but the mechanism for drug-induced destruction is better understood. There are two models for this: the hapten model and the autoantibody model. The hapten model proposes that certain drugs, especially penicillin and cephalosporins, will bind to the red cell membrane and act as haptens. Antibodies are created against the cell-drug complex, leading to the destructive sequence described above. The autoantibody model proposes that, through a mechanism not yet understood, certain drugs will cause antibodies to be made against red blood cells which again leads to the same destructive sequence.

Clinical Findings

Laboratory findings include severe anemia, increased mean corpuscular volume (MCV, due to the presence of a large number of young erythrocytes), and hyperbilirubinemia (from increased red cell destruction) that can be of the conjugated or unconjugated type.

Diagnosis

Diagnosis is made by a positive direct Coombs test, other lab tests, and clinical examination and history. The direct Coombs test looks for antibodies attached to the surface of red blood cells.

Treatment

Corticosteroids and immunoglobulins are two commonly used treatments for warm antibody AIHA. Initial Tx consists of prednisone. If ineffective, splenectomy should be considered. If refractory to both these therapies, consider rituximab, danazol, cyclosphosphamide, azathioprine, or cyclosporine, High dose intravenous immune globulin may be effective in controlling hemolysis, but the benefit is short lived (1-4 weeks), and the therapy is very expensive.

References

• Sacher, Ronald A. and Richard A. McPherson. "Wildman's Clinical Interpretation of Laboratory Tests, 11th edition."
• Kumar, Vinay, Abul Abbas, and Nelson Fausto. "Robbins and Cotran Pathologic Basis of Disease."