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Test Directory - TPMT Thiopurine Methyl Transferase

Please note new units and reference ranges for TPMT activity from 1st August 2010

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

Combined Pathology Blood form (Yellow/Black)

Availability

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. 
Patients should be advised that DNA confirmation may be performed. The only known implication for the genetic variation in TPMT expression is intolerance to thiopurine drugs (see labtestsonline.org.uk for further information).

Turnaround Time

2 weeks

Specimen

Whole blood (EDTA)

Volume

5-10 ml (paediatric 2-5 ml)

Container

Pink top (EDTA) tube

Lab. Handling

Store at 4C without separation. Send by first class post, early in week. (TPMT & send; NOTPM & save)

Causes for Rejection

Unlabelled sample. Not meeting specific criteria for analysis.

Reference Range

Normal: 68 to 150 mU/L

Deficient (less than 10 mU/L): an absolute intolerance to thiopurine drugs.

Low (20 to 67 mU/L): high risk of sensitivity.
TPMT levels of 10 - 19 mU/L may be seen in TPMT deficient patients who have been transfused.

High (>150 mU/L): there is evidence that patients with TPMT levels of approx. 150 mU/L or above are at risk of being 'poor responders', but may benefit from a higher dose than normal.

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Last edited 16/04/14