Optimal Initial Dose Adjustment of Warfarin in Orthopedic Patients

Warfarin sodium is commonly pre-scribed for the prophylaxis and treatment of venous thromboembolism (VTE) and is characterized by a narrow therapeutic window, a marked interindi-vidual variation in dose requirements, and excessive risk of adverse events with over- and underdosing.1 To minimize competing risks, many experts recom-mend initiating warfarin with the antici-pated maintenance dose but offer little ad-vice about how to estimate that dose.1-3 Likewise, dosing algorithms conflict about how to adjust a dose once the inter-national normalized ratio (INR) values become available. Consider a patient with an INR of approximately 1.5 after 3 nightly doses of warfarin (eg, 5 mg per night): some algorithms recommend in-creasing the dose, some suggest reducing it, others recommend continuing the cur-rent dose, and still others allow for more than one action.4-11 Resolution of this con-flicting advice is critical for hundreds of thousands of people beginning warfarin therapy each year for prophylactic treat-ment of VTE after orthopedic surgery.12 Optimal dose adjustment is compli-cated by factors confounding the relationship between INR and warfarin dose. Many drugs interact with warfarin.13 Large intraoperative losses of blood deplete clotting factors and might contribute to elevated postoperative INR values after major surgery.14 There is a critical need to determine the therapeutic war-farin dose after major surgery, where the risks of hemorrhage and thrombosis are markedly increased. The need is especial-ly great in orthopedic patients who are discharged home after 2–3 doses of warfarin on an estimated warfarin dose for VTE prophylaxis.15 We sought to develop and validate algorithms that could help pharmacists and physicians estimate the ther-apeutic warfarin dose after 2–3 days of therapy