Warfarin untargeted metabolomics study identifies novel procoagulant ethanolamide plasma lipids.

Warfarin (Coumadin®) is one of the most widely prescribed anticoagulant drugs used to treat and prevent thrombosis in patients with cardiovascular or other thrombotic disorders (Keeling et al, 2011). Warfarin inhibits vitamin K epoxide reductase and decreases vitamin K hydroquinone to attenuate blood coagulation by inhibiting vitamin K-dependent posttranslational modifications of plasma coagulation factors in the liver. A recent study showed that R-warfarin interacts with the pregnane X receptor (PXR) which is associated with a variety of metabolic clearance functions in vivo (Keeling et al, 2010), suggesting that warfarin could affect a variety of metabolites in addition to vitamin K-related metabolites. There is a paucity of studies about the effects of warfarin on natural plasma metabolites; thus, we sought to identify metabolites that are regulated by warfarin which could affect coagulation.