A patient receiving high-dose intravenous penicillin for endocarditis develops hemolytic anemia. The direct antiglobulin test is positive, and eluted antibody binds red cells only when penicillin is present in the test system. If the drug is stopped, hemolysis resolves over days to weeks. Which mechanism explains this hemolytic anemia?

• A True autoantibody directed against the Rh complex that persists long after drug withdrawal
• B Direct toxic effect of penicillin on the red cell cytoskeleton
• C Immune complex deposition on red cells with bystander complement activation
• D Hapten dependent antibody that binds only the red cell membrane drug complex ✓

Explanation

Penicillin acts as a hapten, coating red cell membranes at high doses, and IgG forms against the drug-membrane complex; the antibody reacts only when drug is present, and hemolysis stops once penicillin clears. Methyldopa instead induces true autoantibodies against Rh antigens that persist weeks to months after withdrawal, which is exactly what option A describes and is the main distractor. Quinine causes immune complex mediated hemolysis, but that classically involves thrombocytopenia more than isolated anemia.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.