Pathology Handbook

TPMT (Thiopurine Methyl Transferase)

Clinical Indications

Thiopurine drugs such as azathioprine, 6-mercaptopurine and thioguanine are converted in vivo to form cytotoxic thionucleotides which provide the therapeutic effect (white cell suppression). 

TPMT provides the major catabolic pathway for these drugs. If the enzyme is absent in the patient there will be an 'over-dosing' effect, frequently resulting in severe bone marrow depression, also nausea.

Complete deficiency of TPMT occurs in 1:300 Caucasians (it is also known in patients of African origin).  Partial deficiency occurs in more than 1:10

Prospective measurement of TPMT provides a rational basis for deciding on levels of thiopurine drug therapy.

Request Form

Request on ICE


Analysed by referral laboratory if specific criteria met.

Specific Criteria

Investigation will normally only be undertaken if patient is about to commence therapy. Repeat requests will not be undertaken unless agreed with the Consultant Biochemist

Patient Preparation

Recent blood transfusions will confuse the enzyme phenotype.
TPMT is inducible so the analysis should be done before commencing therapy.

If the patient is already receiving azathioprine, this must be stated on the request form. 

Turnaround Time

2 weeks


Whole blood (EDTA)


5-10 ml (paediatric 2-5 ml)


Vacutainer gold top

Causes for Rejection

Unlabelled or inadequately labelled  sample.

Not meeting specific criteria for analysis.

Reference range

Whole blood TPMT





20 - 67


68 - 150