Comparison of two different techniques of warfarin dosing determination - A chemometrics study

Document Type: Research article

Authors

1 Department of Chemistry, Faculty of Natural Sciences, University of SS Cyril and Methodius, Trnava, Slovak republic.

2 Department of Pediatric Hematology and Oncology, Comenius University - Faculty of Medicine and National Institute of Children’s Diseases, Bratislava, Slovak republic.

3 Department of Internal Medicine, Slovak Medical University, University Hospital, Bratislava, Slovak republic.

4 Department of Pediatric Hematology and Oncology, Comenius University - Faculty of Medicine and National Institute of Children’s Diseases, Bratislava, Slovak republic .

5 National Hemophilia Center, Department of Hematology and Transfusion Medicine, Faculty of Medicine of the Comenius University and University Hospital, Bratislava, Slovak republic.

Abstract

A high prevalence of genetic polymorphisms increases sensitivity to warfarin therapy. In this study, we investigated 47 patients with effective long-term therapy by warfarin well-controlled by monitoring of International Normalised Ratio (INR). All patients were tested for gene polymorphisms VKORC1, CYP2C9*C2, and CYP2C9*C3, which were used for a dose calculation employing a program www.WarfarinDosing.org. The main goal was to investigate whether the warfarin doses determined by INR are in accordance with the doses calculated according to the pharmacogenetic algorithm. For this purpose, several chemometric tools, namely principal component analysis, cluster analysis, correlation analysis, correspondence analysis, Passing-Bablock regression, Bland-Altman method, descriptive statistics, and ANOVA were used. We also analysed the relationship between the dose of warfarin determined by INR and several constitutional and genetic factors. Statistically significant association between clinically optimized warfarin dose and indication for the treatment, age, and warfarin sensitivity determined by VKORC1, CYP2C9 gene polymorphisms were confirmed. Finally, we confirmed a good concordance between the INR determined warfarin doses and pharmacogenetic approach.

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