Warm Autoimmune Hemolytic Anemia - Pathophysiology

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 exposed with maximal reactivity at 37°C (versus cold antibody induced hemolytic anemia whose antibodies only bind red blood cells at low body temperatures, typically 28-31°C). 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.

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 certain proteins on the red cell membrane and act as haptens (small molecules that can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself). Antibodies are created against the protein-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.

It is possible for it to occur in an immunocompromised patient.