Abstract
Genetic factors most correlated with warfarin dose requirements are variations in the genes encoding the enzymes cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR). Patients receiving warfarin who possess one or more genetic variations in CYP2C9 and VKORC1 are at increased risk of adverse drug events and require significant dose reductions to achieve a therapeutic international normalized ratio (INR). A 74-year-old white female with atrial fibrillation was initiated on a warfarin dose of 2 mg PO daily, which resulted in multiple elevated INR measurements and three clinically significant hemorrhagic events and four vitamin K antidote treatments over a period of less than two weeks. Genetic analysis later revealed that she had the homozygous variant genotypes of CYP2C9∗3∗3 and VKORC1-1639 AA. Warfarin dosing was subsequently restarted and stabilized at 0.5 mg PO daily with therapeutic INRs. This is the first case report of a white female with these genotypes stabilized on warfarin, and it highlights the value of pharmacogenetic testing prior to the initiation of warfarin therapy to maximize efficacy and minimize the risk of adverse drug events.
Highlights
Warfarin is the most widely used anticoagulant in the world and has been consistently shown to be effective at preventing emboli in patients with prosthetic heart valves or atrial fibrillation [1]
Height, weight, gender, race, diet, smoking, comorbidities, prosthetic heart valve, and other medications contribute to the dose variability of warfarin, but genetic factors have been shown to be the largest contributor to the dose variability of warfarin [2, 3]
The two genetic factors that are most correlated with warfarin dose requirements are variations in the genes encoding the enzymes cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR) [1]
Summary
Warfarin is the most widely used anticoagulant in the world and has been consistently shown to be effective at preventing emboli in patients with prosthetic heart valves or atrial fibrillation [1]. The two genetic factors that are most correlated with warfarin dose requirements are variations in the genes encoding the enzymes cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR) [1]. The CYP2C9∗3 variant allele has been shown to cause an 80% decrease in enzymatic activity of CYP2C9 and contributes to the dose variance of warfarin [4]. Patients who are homozygous variant for CYP2C9∗3 and homozygous variant for VKORC1-1639 A are expected to be extremely sensitive to warfarin. Case Reports in Genetics require very low doses of warfarin to achieve appropriate therapeutic effect and minimize risk of adverse drug events. We provide the first case report of a white female with a genotype of CYP2C9∗3∗3 and VKORC1-1639 AA stabilized on the same maintenance dose of warfarin. This report details the clinical course of the patient, summarizes findings from related case reports, and highlights the value of pharmacogenetic testing for warfarin patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
