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 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).

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.

[citation needed] Laboratory findings include severe anemia, normal MCV (mean corpuscular volume), and hyperbilirubinemia (from increased red cell destruction) that can be of the conjugated or unconjugated type.

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.