A 62-year-old man treated with methyldopa for hypertension for 4 months develops hemolytic anemia. Direct antiglobulin test is positive for IgG, and eluted antibody reacts with normal red cells lacking any bound drug. Which mechanism explains this hemolysis?
- A Drug acts as a hapten coating red cells, with antibody binding the membrane-bound drug
- B Drug induces a true autoantibody against red cell antigens, reacting independently of the drug ✓
- C Drug-antibody immune complexes deposit on red cells and fix complement
- D Drug directly denatures the red cell membrane, exposing cryptic phosphatidylserine
Correct answer: B. Drug induces a true autoantibody against red cell antigens, reacting independently of the drug
Explanation
Methyldopa causes the autoantibody type of drug-induced immune hemolytic anemia: the drug alters immune regulation so that IgG autoantibodies, often directed against Rh antigens, are produced. These bind and lyse red cells even when no drug is present on the membrane, which is exactly what the eluate reactivity shows here. Penicillin follows the hapten mechanism (option A) and quinidine follows the innocent bystander immune complex mechanism (option C).
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.