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American Journal of Hematology 67:144–146 (2001) Extreme Warfarin Sensitivity in Siblings Associated With Multiple Cytochrome P450 Polymorphisms Arash Rafii Tabrizi,1 Sean D. McGrath,2 Morey A. Blinder,3 Timothy G. Buchman,1 2 1 Barbara A. Zehnbauer, and Bradley D. Freeman * 1Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 2Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 3Department of Medicine, Washington University School of Medicine, St. Louis, Missouri Warfarin use is complicated by an erratic dose response. Warfarin is metabolized by two distinct subfamilies of the cytochrome P450 (CYP) complex. We describe two siblings with extreme sensitivity to warfarin who share an unusual CYP genotype. These indi- viduals illustrate both the importance of genetics in influencing the metabolism of war- farin as well as the potential utility of genetic testing as a guide to prescribing this medication. Am. J. Hematol. 67:144–146, 2001. © 2001 Wiley-Liss, Inc. Key words: warfarin; cytochrome P450 complex; siblings INTRODUCTION with control plasma, consistent with clotting factor defi- ciency. Her hepatic function profile, serum albumin, and Warfarin is one of the most frequently prescribed
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