title: Use of signals and systems engineering to improve the safety of warfarin initiation.
abstract: Warfarin-dosing algorithms combine clinical factors and dosing history with the current international normalized ratio (INR) to estimate the therapeutic warfarin dose. Unfortunately, these approaches can result in an overdose if the INR is spuriously low. Our goal was to develop an alert mechanism based on prior INRs in addition to the current INR. Using data from the Genetics InFormatics Trial (GIFT) of Warfarin to Prevent DVT, we analyzed warfarin dose estimates for days 3 through 11 that were ≥10 % higher than an average of the previous two dose estimates. We fit a stepwise mixed model to current and prior dose estimates, and subsequently compared the root-mean-square-error (RMSE) in predicting the final therapeutic dose using the GIFT algorithm versus the mixed model. From 861 dosing records (obtain from 556 patients), 646 dosing records (75 %) were randomly selected for the derivation cohort and 215 dosing records (25 %) for the validation cohort. Using one prior dose estimate improved the accuracy of the warfarin dose estimate. Compared to a dose estimate based on current INR (GIFT algorithm), the mixed model reduced the RMSE in the derivation cohort by 0.0015 mg/day (RMSE 0.2079 vs. 0.2094; p = 0.039). In the validation cohort, the RMSE reduction was not significant. A mixed model of dose estimates based on the current and most recent INRs shows potential to improve the safety of warfarin dosing. Clinicians should be cautious about aggressively escalating the warfarin dose after an INR that is lower than expected.
authors.affiliation: Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8005, St. Louis, MO, 63110, USA.
authors.forename: G
authors.initials: G
authors.lastname: Hyun
authors.affiliation: Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8005, St. Louis, MO, 63110, USA.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Hospital for Special Surgery, Weill Cornell Medical College, 535 E 70th Street, New York, NY, 10021, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Bass
authors.affiliation: Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8005, St. Louis, MO, 63110, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mohapatra
authors.affiliation: Intermountain Medical Center, 5121 Cottonwood St, Murray, UT, 84157, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Woller
authors.affiliation: Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8005, St. Louis, MO, 63110, USA.
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.affiliation: Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8005, St. Louis, MO, 63110, USA.
authors.forename: C
authors.initials: C
authors.lastname: Eby
authors.affiliation: Department of Pathology and ARUP Laboratories, University of Utah, 500 Chipeta Way, Salt Lake City, UT, 84108, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: McMillin
authors.affiliation: Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8005, St. Louis, MO, 63110, USA. bgage@dom.wustl.edu.
authors.forename: B F
authors.initials: BF
authors.lastname: Gage
mesh_terms: D000368:Aged; D000465:Algorithms; D005260:Female; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods*; D008297:Male; D008955:Models, Cardiovascular; D020246:Venous Thrombosis / Q000097:blood / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D014859:Warfarin
keywords: Dosing algorithm; INR; Overdose; Patient safety; Warfarin