Warfarin Initiation and the Potential Role of Genomic-Guided Dosing

Substantial inter-patient variability exists in the anti-thrombotic response to warfarin. This statement, an observation well known among clinicians and investigators, is a reflection of the wide range of warfarin maintenance doses observed across the population, often ranging anywhere from 1 mg/day to 20 mg/day. Consequently, warfarin therapy requires intensive monitoring via the International Normalized Ratio (INR) to guide its dosing, to maintain a therapeutic level of anti-thrombosis and to minimize the risk of bleeding.1 Most would agree that once anti-thrombotic stability is attained and a maintenance dose is identified, clinicians are effectively able to maintain a therapeutic INR and minimize adverse bleeding. However, the initiation phase of warfarin therapy, the time when a patient’s chronic maintenance dose requirement is unknown, remains the critical dosing period with the greatest degree of uncertainty and risk for adverse events. Over the years, clinicians have utilized demographic and clinical information such as age, concomitant medication use and dietary vitamin K intake, as well as various dosing nomograms to help predict an individual patient’s warfarin dose requiremen