Erythrocyte thiopurine methyl transferase assessment prior to azathioprine use in the UK

Background: Individuals with low activity of a key metabolic enzyme, thiopurine methyl transferase (TPMT), are more susceptible to azathioprine-induced myelosuppression. Aim: To determine the pattern of use of TPMT activity estimation, with respect to azathioprine use, by medical practitioners in the UK. Design: Retrospective analysis of assay use. Methods: We analysed all test results (n=3291), and patient and practitioner details, from inception of TPMT assay in 1990 to the end of December 2000, held at the Purine Research Laboratory, Guy's Hospital, London. Patient details were anonymized. Repeat analyses and requests from outside the UK were excluded. Results: The male:female ratio was approximately equal and the mean age was 46.6 (range 0.5-97) years. Thirteen different medical specialities requested assays; Dermatology and Gastroenterology were the most frequent users, together accounting for 86% of requests. The numbers of centres requesting the assay varied widely both within and between different specialities. Some 80% of individuals had normal TPMT activity, 9% enzymic activity above normal, and 10% low activity. Fifteen had no detectable enzymic activity: 0.45% (1:220) of the study population. Discussion: This incidence of undetectable enzyme activity is significantly higher than the previously reported level of 1:300 derived from smaller studies, and makes the economics of screening more attractive.