1Order UGT1A1 genotyping and discontinue complete blood count monitoring once the result is available.
2Order HLA-B*57:01 testing and increase azathioprine if the result is negative.
3Measure G6PD activity and continue the current dose while the leukocyte count recovers.
4Evaluate TPMT and NUDT15 status, continue CBC monitoring, and review dose reduction or alternative therapy.✓ Correct answer
Explanation
Reduced TPMT or NUDT15 activity increases exposure to active thiopurine metabolites and the risk of severe myelosuppression. In a client with severe or recurrent cytopenias, genotyping or phenotyping for TPMT and genotyping for NUDT15 can inform dose reduction or alternative therapy. Genetic or enzyme testing does not replace serial complete blood count monitoring. UGT1A1, HLA-B*57:01, and G6PD testing address different medication risks.
Clinical reasoning Azathioprine is converted to 6-mercaptopurine metabolites. Low TPMT or NUDT15 activity permits accumulation of active thioguanine nucleotides and profound marrow toxicity at conventional doses.
Decision rule With severe or repeated azathioprine myelosuppression, evaluate TPMT and NUDT15, continue CBC surveillance, and adjust or replace therapy according to the clinical and genetic findings.
Scenario A client receiving azathioprine develops severe recurrent leukopenia despite dose reduction. The prescriber is evaluating an inherited risk for thiopurine toxicity.
TPMT deficiency — Reduced thiopurine S-methyltransferase activity that increases active thiopurine metabolites and myelotoxicity risk.
NUDT15 deficiency — Reduced nucleotide diphosphatase activity associated with marked thiopurine intolerance and myelosuppression.
NUDT15 — Pharmacogenomic gene with higher impact in Asian populations than TPMT.