Warfarin Dosing Algorithm Now Available

Polymorphisms in the VKORC1 (vitamin K epoxide reductase) gene explain 25% of the dose variation between patients: particular mutations make VKORC1 less susceptible to suppression by warfarin. CYP2C9 (cytochrome P450) polymorphisms explain another 10%. VKORC1 polymorphisms also explain why African Americans are relatively resistant to warfarin, while Asian Americans are more sensitive.

Realizing that no existing algorithm provided recommendations for refining the initial warfarin dose based on genetic variables, clinical data, and international normalized ratio (INR) values, investigators at Washington University School of Medicine (St. Louis, MO, USA) decided to develop one. They collected blood samples, clinical variables, current medications, and preoperative and postoperative laboratory values from 92 patients undergoing primary or revision total hip or knee replacement. In addition, they determined genotypes for polymorphisms in the CYP2C9 and VKORC1 genes.

"We already knew these genes affected warfarin dosing, but we did not know how to use that information clinically,” said senior author Dr. Brian Gage, associate professor of medicine at Washington University School of Medicine. "But with this study, we have established a simple way to combine these genetic factors with clinical factors in a dosing algorithm.”

The new algorithm was published in the September 1, 2007, issue of Blood and has been made available to physicians over the Internet.


Related Links:
Washington University School of Medicine
Warfarin Dosing Algorithm