WARFARIN SENSITIVITY DETECTION

WARFARIN IS A COUMARIN-BASED ANTICOAGULANT DRUG USED TO PREVENT THROMBOSIS DUE TO INHERITED AND ACQUIRED HEMOSTATIC DISORDERS. IT IS ALSO USED IN OTHER CONDITIONS LIKE ATRIAL FIBRILLATION AND HIP REPLACEMENT SURGERY. WARFARIN THERAPY HAS ONE OF THE HIGHEST RATES OF SEVERE REACTIONS. ITS METABOLISM IS HIGHLY VARIABLE AND DEPENDENT UPON GENETIC FACTORS. VARIANTS WITHIN 3 GENES AND 1 INTRAGENIC LOCUS ARE KNOWN TO AFFECT THE METABOLISM OF WARFARIN.THE CYP2C9 GENE ENCODES THE ENZYME WHICH PRIMARILY METABOLIZES THE MORE ACTIVE ISOMER OF WARFARIN TO INACTIVE PRODUCTS. SOME CYP2C9 VARIANTS RESULT IN DECREASED ENZYMATIC ACTIVITY AND MAY LEAD TO INCREASE IN SERUM LEVELS AND OVER-MEDICATION. THE DECREASED EXPRESSION OF VKORC1 GENE, RESULTS IN REDUCED AVAILABILITY OF VITAMIN K. THIS MAY ALSO INCREASE SERUM WARFARIN AND LEAD TO OVERMEDICATION, DRIVING THE INR ABOVE THE THERAPEUTIC TARGET.