Yim, A.; Holmes, A.; Ansari, A.; Arenas, M.; Shobowale, E.M.; Marinaki, A.; Duley, J.A.; Sanderson, J.D.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA39
Academic Journal
Background and Aims: Detection of a zero TPMT activity prior to commencing azathioprine (AZA) avoids the risk of severe and potentially fatal myelosuppression. Zero TPMT activity has been estimated as 1:300 in a Caucasian population. The aim of this study was to define the distribution of TPMT activity among patients referred from throughout the UK to a National Purine Reference laboratory. Methods: TPMT data were obtained from the first assay in 1990 to present. Where available, data on AZA treatment and referring centre were recorded. Results: TPMT demand has risen exponentially since 1990. 500/ year were perfomed in 1998 and 7500 so far in 2002. Requests from gastroenterologists have increased from 34% to 51% in the same period. From an analysis of 5000 consecutive requests, the frequency for zero TPMT activity was 1:210-220 (0.45%). This figure remained 0.45% when only those who had not started AZA treatment were analysed (n = 1747). The mean and median were 32.3 units. The intermediate activity (between 10-25 units) frequency was 16%. This is also higher than previously reported (11%) although it is known that not all intermediates are carriers. TPMT activity was distributed non-normally, with two "shoulders" to the main curve. At the lower end of TPMT activity (10-20 units), the heterozygote deficient group form a distinct group. At the high end of activity there is reproducible shoulder that maybe a separate genetic entity. Conclusions: TPMT requests have increased exponentially throughout the UK, especially from gastroenterologists. Zero TPMT frequency is probably higher than predicted from previous studies. This has important cost implications for those seeking financial justification for checking TPMT prior to commencing AZA. At 1 in 220, it would cost £8800 to prevent each episode of potentially fatal myelotoxicity.


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