Article Text

What is the benefit of measuring erythrocyte thiopurine transmethyltransferase activity in children?
  1. H Aitkenhead3,
  2. S Patey2,
  3. SD Marks1,
  4. ALT Ma1,
  5. G Bale2
  1. 1Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Trust, London, UK
  2. 2Pharmacy, Great Ormond Street Hospital for Children NHS Trust, London, UK
  3. 3Clinical Pathology, Great Ormond Street Hospital for Children NHS Trust, London, UK


Aim Azathioprine is an effective immunosuppressive agent for the management of a wide spectrum of diseases, including systemic lupus erythematosus, vasculitis and in renal transplantation. Myelosuppression is a known major side-effect so some authors advocate that erythrocyte thiopurine transmethyltransferase (TPMT) activity is required to identify those patients at increased risk. In such cases, the azathioprine dosage can be adjusted prior to prescribing. However, there is a lack of data to support routine TPMT monitoring in paediatric patients.

Methods Retrospective study in a single paediatric centre of all patients who had TPMT enzyme assay measured over a three year period prior to the commencement of azathioprine therapy. Patients with TPMT enzyme activities of 26-50, 10-25 and <10 pmol/h/mgHb were classified as normal, intermediate and deficient, respectively. Medical and electronic prescribing records were studied with record of patients' demographic data, diagnoses, dosages, and adverse drug reactions were monitored.

Results 363 (51% female) patients aged 1-19 (median 10.2) years were tested for TPMT activity of whom 228 patients were subsequently commenced on azathioprine. Erythrocyte TPMT activities were 14-76 (median 33.7) pmol/h/mgHb with 88% and 12% of patient having normal and intermediate activity respectively (none were deficient). The initial prescribed dosage of azathioprine was 0.7-3.5 (median 2.0) mg/kg/day. Only two patients required reduction of azathioprine dosage due to mild neutropenia in this cohort.

Conclusion This is the first large paediatric cohort study which demonstrates that the majority of paediatric patients had normal TMPT activities and no patients developed severe neutropenia as a result of azathioprine treatment. We estimate the cost for testing this patient cohort was £16,000 without clinical benefit. We would recommend close monitoring of full blood counts after instituting azathioprine therapy but would question the value of pre-treatment TPMT activity in paediatric practice.

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