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Abstract
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.
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Fig. 1.
Chromatograms of 7-hydroxywarfarin (m/z 322.9 → 176.8), warfarin (m/z 307.0 → 160.9), and internal standard (chlorowarfarin; m/z 340.9 → 283.8).
Fig. 2.
Correlation of PT INR, plasma warfarin concentration, and warfarin dose. Abbreviation: PT INR, prothrombin time international normalized ratio.
Fig. 3.
(A) The distributions of warfarin dose in 74 patients with PT INR within the target range of 2.0-3.0. (B) The total warfarin concentrations and the middle 95th percentile interval (0.6-2.6 mg/L) in this group. (C) The plasma warfarin to 7-hydroxywarfarin concentration ratio in this group. The vertical lines indicate the extent of normal distribution of the data.
Table 1.
Characteristics of patients with atrial fibrillation (N=105)
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