Genetics of Warfarin Sensitivity in an Emergency Department Population with Thromboembolic

BACKGROUND: Emergency department (ED) patients with venous thromboembolism (VTE) are eventually treated with a standard dose of warfarin despite the fact that a number of patients are known to be sensitive to warfarin and may experience supra-therapeutic INRs and adverse bleeding events. Pharmacogenetics is an emerging field of medical practice that seeks to improve drug safety and efficacy in an individual patient by tailoring treatment to the patient’s known genetic makeup. OBJECTIVE: To identify patients with risk for warfarin sensitivity among an ED population with VTE and to assess if the warfarin sensitivity mutations were of significant enough prevalence to be of clinical significance in customizing treatment of VTE. We sought in a pilot study to identify if testing for common CYP2C9 and VKORC1 single nucleotide polymorphisms (SNPs) in patients who were likely to begin warfarin treatment was feasible in an ED setting. METHODS: A prospective study that identified and enrolled patients presenting to our ED with high clinical suspicion of VTE. Those with high clinical suspicion of VTE were defined as those who had a Doppler ultrasound or computed tomography pulmonary angiography (CTPA) ordered by the primary emergency physician. Blood was taken and processed to ascertain the following SNPs: CYP2C9*2, CYP2C9*3, and VKORC1 3673. RESULTS: Of the 194 patients enrolled, 132 (68.0%) had at least one known warfarin sensitivity mutation and 114 (58.8%) had the most clinically significant VKORC1 3673 mutation. CONCLUSION: A majority of our patients had at least one mutation associated with the atypical metabolism of warfarin. Over half of our population had the most clinically significant VKORC1 3673 mutation. They would likely benefit from individualized warfarin dosing if ever needing anticoagulation. Our initial pilot study shows that allele frequencies of target warfarin sensitivity SNPs in our patient population are frequent enough to make initiation of personalized warfarin dosing feasible.