BACKGROUND: Warfarin is a widely used oral anticoagulant with broad within- and between-individual dose requirements. Warfarin concentrations can be monitored by assessing its pharmacologic effects on International Normalized Ratio (INR). However, this approach has not been applied in the routine clinical management of patients receiving warfarin therapy. We performed a plasma warfarin assay using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) to determine if such an assay can be utilized in routine clinical practice. METHODS: We included a total of 105 patients with atrial fibrillation, and who were receiving warfarin for more than 1 yr. The plasma concentrations of total warfarin and 7-hydroxywarfarin were determined by HPLC-MS/MS (Waters, UK). We assessed the association between warfarin dose, concentration, and INR as well as the effects of these factors on warfarin concentrations. RESULTS: The mean maintenance dose of warfarin in 105 patients was 4.1+/-1.3 mg/day (range, 1.7-8.0 mg/day) and their mean plasma warfarin concentration was 1.3+/-0.5 mg/L. We defined a concentration range of 0.6-2.6 mg/L (corresponding to the 2.5th to 97.5th percentile range of the Plasma warfarin levels in the 74 patients showing INR within target range) as the therapeutic range for warfarin. The correlation of warfarin dose with warfarin concentration (r2=0.259, P<0.001) was higher than that with INR (r2=0.029, P=0.072). CONCLUSIONS: There was a significant correlation between warfarin dose and plasma warfarin concentrations in Korean patients with atrial fibrillation. Hence, plasma warfarin monitoring can help determine dose adjustments and improve our understanding of individual patient response to warfarin treatment.
Adult ; Aged ; Aged, 80 and over ; Anticoagulants/*blood/therapeutic use ; Asian Continental Ancestry Group ; Atrial Fibrillation/drug therapy ; Chromatography, High Pressure Liquid ; Female ; Humans ; Male ; Middle Aged ; Republic of Korea ; Tandem Mass Spectrometry ; Warfarin/analogs & derivatives/*blood/metabolism/therapeutic use

A 73-yr-old Korean man with permanent atrial fibrillation visited outpatient clinic with severely increased International Normalized Ratio (INR) values after taking a usual starting dosage of warfarin to prevent thromboembolism. We found out later from his blood tests that he had hyperthyroidism at the time of treatment initiation. His genetic analysis showed CYP2C9*1/*3 and VKORC1+1173TT genotypes. We suspect that both hyperthyroidism and genetic variant would have contributed to his extremely increased INR at the beginning of warfarin therapy. From this case, we learned that pharmacogenetic and thyroid function test might be useful when deciding the starting dosage of warfarin in patients with atrial fibrillation.
Aged ; Anticoagulants/blood/metabolism/therapeutic use ; Aspirin/therapeutic use ; Atrial Fibrillation/*diagnosis ; Chromatography, High Pressure Liquid ; Cytochrome P-450 CYP2C9/*genetics ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide ; Tandem Mass Spectrometry ; Thromboembolism/prevention & control ; Thyrotoxicosis/*diagnosis ; Vitamin K Epoxide Reductases/genetics ; Warfarin/*blood/metabolism/therapeutic use