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Warfarin “Resistance”

I’ve had several discussions with Marisa Marques, MD, my friend and colleague in Laboratory Medicine at the University of Alabama at Birmingham about “warfarin resistance,” as she was managing two deep vein thrombosis patients, one of whom required warfarin at 25 mg/day and one at 35 mg/day. We were looking for a polymorphism associated with a need for increase warfarin dosage, but could find none. I confirmed this by phone with Elaine Lyon, PhD, Scientific Director at ARUP in November. However..

In the April 15 edition of Blood, Dr. Michael D. Caldwell’s team at the Marshfield Clinic, Marshfield, WI, in association with Affymetrix, Inc and Third Wave Technologies, described a CYP4F2 variant that in the homozygous form requires approximately a 1 mg/day increase in warfarin dosage. This appears to be the first single nucleotide polymorphism associated with an increased warfarin dosage requirement, and opens a new pathway in pharmacogenomic research. The reference is Caldwell MD, Awad T, Johnson JA, et al. CYP4F2 genetic variant alters required warfarin dose. Blood 2008;111:4106-12. Geo

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