The International Warfarin Pharmacogenetics Consortium recently published the results of their large retrospective study (IWPC, N Engl J Med 360:753-764, 2009). These data strongly support the employment of a pharmacogenetic-based warfarin dosing algorithm to improve warfarin safety. Use of the pharmacogenetic-based algorithm produced dose recommendations that were significantly closer to the stable therapeutic dose than did an algorithm based on clinical data alone or a fixed-dose approach. As another measure of benefit, the number of patients for which genotyping would yield a recommended dose that was within 20% of the actual therapeutic dose while the other algorithm or fixed-dose approach did not was 13. However, only 6% of the patients included in this large, multicenter study were under 40 years of age. The IWPC clearly stated that additional research was needed with respect to the development of a similar algorithm for children and young adults. The proposed research will fill this important knowledge gap.
Completion of the proposed study will provide a robust algorithm that will incorporate genetic differences into guidelines for the use of the anti-blood clotting drug, warfarin, in children. Use of this algorithm will result in a reduction of warfarin-induced adverse drug reactions in this patient population. Further, the completed study will improve our understanding of factors underlying differences in the way adults and children respond to warfarin therapy.
