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Changes to Cheltenham A&E in response to industrial action

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TPMT (Thiopurine methyl transferase)

Chemical Pathology

Notes

  • Thiopurine drugs are widely used in the treatment of inflammatory and autoimmune diseases, leukaemia and prevention of rejection post organ transplant.
  • Thiopurines are catabolised to inactive metabolites by thiopurine methyl transferase (TPMT), which in effect reduces concentrations of the active metabolite, 6-thioguanine nucleotides (6TGN).
  • TPMT activity exhibits genetic variation. In a Caucasian population approximately 89% have normal enzyme activity, 11% low activity and 0.3% undetectable levels (deficient).
  • Measurement of TPMT activity should be performed prior to starting thiopurine drugs. Patients with undetectable activity are generally not treated with thiopurine drugs due to the increased risk of severe side effects including myelosuppression.
  • Recent blood transfusions can affect results and may mask a deficient TPMT.
  • Patients already receiving thiopurine drugs can show enzyme induction leading to increased TPMT activity.

Sample requirements

For adults, 4 ml of blood taken into an EDTA tube a Full Blood Count should also be requested.

EDTA with cap





Storage/transport

Send at ambient temperature to the laboratory. If unavoidable samples can be refrigerated overnight.

Required information

Relevant clinical details including reason for the request and whether any treatment started. Please state if any blood transfusion given in the last 4 months.

Turnaround times

Samples are sent for analysis to St Thomas' Hospital London with results expected back within 10 days.

Reference ranges and Result Interpretation

Whole blood TPMT activity Reference range (nmol/h/g Hb)
Deficient <10
Carrier 10 - 25
Normal 26 - 50
Raised >50

NB: remember enzyme activity may have been induced if patient has already begun treatment.

  • Complete TPMT deficiency (TPMT <10 nmol/h/g Hb) indicates that there is an absolute intolerance to thiopurine drugs.
  • Low activity indicates partial enzyme deficiency and therefore that the probability of azathioprine-induced bone marrow depression or nausea is HIGH. the patient may tolerate a low/normal dose but must be closely monitored for possible bone marrow suppression.
  • Normal enzyme activity indicates that the probability of azathioprine-induced bone marrow depression is LOW. This excludes TPMT deficiency as a cause for acute azathioprine intolerance.
  • TPMT activity of 10 - 19 nmol/h/g Hb may be seen in TPMT deficient patients who have received a blood transfusion.

Further information

Genotyping may be performed by St Thomas' Hospital in certain situations, for example, where a patient has received a blood transfusion which might affect the TPMT activity, or for confirmatory purposes in patients showing an undetectable TPMT activity.

To learn more about TPMT visit

Lab Tests Online

Page last updated 29/12/2023

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