Thiopurine Methyl Transferase (TPMT) activity (and genotyping)
This enzyme controls the rate of metabolism of thiopurine drugs. Used as a predictive test for azathioprine sensitivity. TPMT activity should be determined before starting therapy, however, the test can be performed if patient is already on treatment. Repeat requests for TPMT are not usually indicated and repeat samples will be rejected unless discussed with the laboratory first. TPMT activity is measured by the laboratory at City Hospital, Birmingham. TPMT genotype analysis will be reflexed by the Birmingham laboratory in certain circumstances (including low TPMT activity and low sample haematocrit).
|Tube||03 (EB) - EDTA Blood|
|Additional Information||Thiopurine drugs (azathioprine and 6-mercaptopurine) are converted in vivo to cytotoxic thionucleotides which cause white cell supression. The enzyme TPMT provides a major catabolic pathway for these drugs. In the absence of TPMT activity there will be an over-dose effect, resulting in complete bone marrow supression. 1 in 300 caucasians has complete deficiency of TPMT which results in absolute intolerance to azathioprine. A partial deficiency of TPMT occurs in 1 in 10 of the population and these patients are at high risk (>60%) from azathioprine intolerance. Although patients on azathioprine have FBC monitored regularly it is useful to assess their TPMT status prior to the initiation of therapy. Another group of patients exist who have normal erythrocyte TPMT activity but still display sensitivity to azathioprine. The majority of these are probably intolerant to imidazole (azathioprine is actually a pro-drug for 6-mercaptopurine which is released in the gut when the imidazole moiety is cleaved from azathioprine). The rest of these patients may be intolerant to azathiporine despite normal activity of TPMT due to counter-indicated drugs (e.g Allopurinol), inherited xanthine oxidase deficiency (exclude by confirming normal plasma uric acid), intercurrent viral infection, deficiency of purine 5-nucleotidase.|
|Turn Around||Turnaround time stated by City Hospital, Birmingham: 1 working day|
|Send to||Blood Sciences LGI
(Test referred to: City Hospital, Birmingham)
|Contact||For further details please contact Leeds Pathology customer services: email@example.com.|
|Collection Con||Minimum Volume: 0.5 mL
Instructions to lab: DO NOT CENTRIFUGE. Store in fridge. DO NOT FREEZE. Lithium heparin whole blood also acceptable for TPMT (but not for TGN).
|Ref. Range Notes||< 10 mU/L: deficient. 20-67: low activity. 68-150: normal activity. >150: high activity|
|Telepath||LGI superset LTPMT. SJUH superset JTPMT.|