Current dosing algorithms do not account for genetic and environmental factors for warfarin dose determinations. This study investigated the contribution of age, CYP2C9 and VKORC1 genotype, and body size to warfarin-dose requirements. Studied were 297 patients with stable anticoagulation with a target international normalized ratio (INR) of 2.0 to 3.0. Genetic analyses for CYP2C9 (*2 and *3 all...

The objective was to investigate the incidence of thromboembolic stroke in patients with chronic kidney disease (CKD) and atrial fibrillation (AF) treated with and without warfarin. We investigated the incidence of thromboembolic stroke and of major bleeding in 399 unselected patients with CKD and AF treated with warfarin to maintain an international normalized ratio (INR) between 2.0 and 3.0 (...

To evaluate the interaction of phenylbutazone with racemic warfarin or R,S-(+/-)-warfarin in man, S-(-)-warfarin or levowarfarin was synthesized with (13)C label in the 2-position of the coumarin nucleus and added to [(12)C]R(+)-warfarin or dextrowarfarin to form a [(12)C/(13)C]pseudoracemate of warfarin. In six normal human subjects, a single oral dose of this "cold labeled" pseudoracemate, 1....

Fetal warfarin syndrome is a consequence of maternal intake of warfarin during pregnancy and comprises a wide range of manifestations, including some typical facial dysmorphologic features. The authors report a case of prenatal ultrasonographic diagnosis of warfarin embryopathy in an obese woman on unsupervised warfarin prophylaxis at the 16th week of gestation. The fetus presented with facial ...

Warfarin is commonly used to prevent stroke in patients with atrial fibrillation; however, patients on haemodialysis may not derive the same benefit from warfarin as the general population. There are no randomized controlled studies in dialysis patients which demonstrate the efficacy of warfarin in preventing stroke. In fact, warfarin places the dialysis patient at increased risk for haemorrhag...

In the 1970s an interaction between metronidazole and warfarin was described in healthy volunteers. Subsequently, there have been few reports describing the interaction during the concurrent administration of warfarin and metronidazole. A critical analysis of warfarin interactions concluded that the metronidazole-warfarin interaction is “highly probable”, with metronidazole potentiating the ant...

BACKGROUND Vitamin K epoxide reductase subunit 1 (VKORC1) is the molecular target of coumarin anticoagulants and mutations in VKORC1 have been identified previously in individuals who required high warfarin doses. OBJECTIVE Detailed characterization of the relationship between variation in VKORC1 and the warfarin resistance phenotype. PATIENTS AND METHODS Serum warfarin concentration and co...

BACKGROUND Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disea...

BACKGROUND Warfarin is an anticoagulant and is widely used for the prevention of thromboembolic events. Genetic variants of the enzymes that metabolize warfarin, i.e. cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various warfarin doses. There is, however, a dearth of data on the role of these variants during initial an...

BACKGROUND Bleeding is the most common and worrisome adverse effect of warfarin therapy. One of the factors that might increase bleeding risk is initiation of interacting drugs that potentiate warfarin. We sought to evaluate whether initiation of an antidepressant increases the risk of hospitalization for gastrointestinal bleeding in warfarin users. METHODOLOGY/PRINCIPAL FINDINGS Medicaid cla...