Clozapine requires mandatory weekly white blood cell monitoring due to which potentially fatal side effect?
- A Agranulocytosis, occurring in 1–2% of patients due to toxic metabolite-mediated destruction of granulocyte precursors ✓
- B Aplastic anaemia caused by direct bone marrow suppression via dopamine D4 receptor blockade
- C Thrombocytopenia due to platelet serotonin receptor antagonism
- D Haemolytic anaemia caused by complement-mediated red cell destruction
Correct answer: A. Agranulocytosis, occurring in 1–2% of patients due to toxic metabolite-mediated destruction of granulocyte precursors
Explanation
Clozapine causes agranulocytosis (absolute neutrophil count < 500/mm³) in 1–2% of patients, typically within the first 6 months. The mechanism involves reactive metabolites (nitrenium ions) of clozapine formed by myeloperoxidase in neutrophils that covalently bind to proteins, triggering immune-mediated destruction of granulocyte precursors. Weekly WBC/ANC monitoring is mandatory; clozapine must be discontinued if ANC falls below 1500/mm³.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.