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Azathioprine TPMT Myelosuppression — RACP Adult Medicine MCQ

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ModerateClinical PharmacologyAzathioprine TPMT MyelosuppressionRACP Adult Medicine

A 60-year-old woman with autoimmune hepatitis on prednisolone and azathioprine develops leucopaenia (WCC 2.0 × 10⁹/L) with an isolated low neutrophil count. Her TPMT activity was not tested before starting azathioprine. What is the most likely cause?

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Correct answer: C — Azathioprine-induced myelosuppression due to low TPMT activity

Azathioprine is metabolised by thiopurine methyltransferase (TPMT). Approximately 10% of the population has intermediate TPMT activity and 0.3% has absent activity, predisposing to severe myelosuppression on standard doses. TPMT genotyping or phenotyping should be performed BEFORE starting azathioprine. If TPMT is low, the dose must be significantly reduced or an alternative used. NUDT15 testing is also relevant, especially in patients of East Asian descent.

Reference: AMH – 2025 – Azathioprine; eTG – 2025 – Gastrointestinal