Chapter 26: Drug-Induced Hemolytic Anemia

ETIOLOGY AND PATHOGENESIS

• Table 26–1 lists the drugs implicated in the production of a positive direct antiglobulin test and accelerated red cell destruction.

• Three mechanisms of drug-related immunologic injury to red cells are defined:

  — Hapten/drug adsorption involving drug-dependent antibodies.

  — Ternary complex formation involving drug-dependent antibodies.

  — Induction of autoantibodies that react with red cells in the absence of the inciting drug.

• Drug-related nonimmunologic protein adsorption may also result in a positive direct antiglobulin test without red cell injury.

HAPTEN OR DRUG ADSORPTION MECHANISM

• Occurs with drugs that bind firmly to red cell membrane proteins. Penicillin is the classic example.

• In patients receiving high-dose penicillin, red cells have a substantial coating of the drug. In a small proportion of patients, an antipenicillin antibody (usually IgG) develops and binds to the penicillin on the red cell. The direct antiglobulin test then becomes positive and hemolytic anemia may ensue.

• Hemolytic anemia caused by penicillin typically occurs after 7 to 10 days of treatment and ceases a few days to 2 weeks once the drug is stopped.

• Other manifestations of penicillin allergy are usually not present.

• Antibody-coated ("opsonized") red cells are destroyed mainly in the spleen.

• Antibodies eluted from red cells, or present in sera, react only against penicillin-coated red cells. This specificity distinguishes drug-dependent antibodies from true autoantibodies.

• Hemolytic anemia similar to that seen with penicillin has also been ascribed to other drugs (see Table 26–1).

TERNARY COMPLEX MECHANISM: DRUG-ANTIBODY TARGET-CELL COMPLEX

• The mechanism of red cell injury is not clearly defined, but it appears to be mediated by a cooperative interaction to generate a ternary complex involving the drug or drug-metabolite, a ...