A 45-year-old woman on methyldopa for hypertension develops fatigue and jaundice. CBC shows Hb 8.2 g/dL, MCV 102 fL, reticulocyte count 9.8%, indirect bilirubin 3.4 mg/dL. Direct Coombs test is strongly positive (IgG warm antibodies). The mechanism by which methyldopa induces hemolytic anemia is:
- A Hapten mechanism — methyldopa binds RBC membrane proteins and acts as hapten
- B True autoimmunity — methyldopa alters immune regulation, generating anti-Rh IgG autoantibodies without drug involvement ✓
- C Innocent bystander mechanism — complement activation by drug-Ab complexes on RBC surface
- D Drug-dependent antibody mechanism — antibodies only recognize drug-RBC complex
Explanation
Methyldopa-induced immune hemolytic anemia is the classic example of the true autoimmunity mechanism. Methyldopa modifies T-lymphocyte function, resulting in loss of self-tolerance and generation of true anti-RBC autoantibodies (usually anti-Rh specificity, anti-e or anti-c). Critically, these autoantibodies can agglutinate native RBCs even in the absence of the drug — they are true autoantibodies. This distinguishes the methyldopa mechanism from drug-dependent antibodies (hapten: penicillin; innocent bystander: quinine; drug-dependent immune complex mechanism). The DAT is positive for IgG; stopping methyldopa leads to resolution over weeks to months. Approximately 15% of patients on methyldopa develop positive DAT, but only 1% develop hemolysis.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.