A New Approach towards Minimizing the Risk of Misdosing Warfarin Initiation Doses.

Ashkan Sharabiani,Edith A Nutescu,Houshang Darabi,William L Galanter

doi:10.1155/2018/5340845

Ashkan Sharabiani, Edith A Nutescu + Show 2 more

Open Access

https://doi.org/10.1155/2018/5340845

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Abstract

It is a challenge to be able to prescribe the optimal initial dose of warfarin. There have been many studies focused on an efficient strategy to determine the optimal initial dose. Numerous clinical, genetic, and environmental factors affect the warfarin dose response. In practice, it is common that the initial warfarin dose is substantially different from the stable maintenance dose, which may increase the risk of bleeding or thrombosis prior to achieving the stable maintenance dose. In order to minimize the risk of misdosing, despite popular warfarin dose prediction models in the literature which create dose predictions solely based on patients' attributes, we have taken physicians' opinions towards the initial dose into consideration. The initial doses selected by clinicians, along with other standard clinical factors, are used to determine an estimate of the difference between the initial dose and estimated maintenance dose using shrinkage methods. The selected shrinkage method was LASSO (Least Absolute Shrinkage and Selection Operator). The estimated maintenance dose was more accurate than the original initial dose, the dose predicted by a linear model without involving the clinicians initial dose, and the values predicted by the most commonly used model in the literature, the Gage clinical model.

Highlights

Warfarin is a commonly used oral anticoagulant drug with over 30 million prescriptions written annually in the UnitedStates [1]
The objective of this paper is to propose a method to minimize warfarin misdosing when the prescription of the initial dose is guided by clinical judgment alone
If the resulting dose from the Gage clinical model [3] which is calculated using data in the electronic medical record (EMR) and the dose selected by the clinician are more than 20% different from the calculated dose, a warning is shown to the ordering clinician which includes the suggested dose

Summary

Introduction

This drug is difficult to manage because of its narrow therapeutic index and wide interpatient variability in dose response. Warfarin is the leading cause of drugrelated hospitalizations among adults in the United States [2]. There are numerous factors affecting the activity of warfarin. They vary from each individual patient’s characteristics, such as height, weight, age, and race, to the patient’s medical history, diet, genotype, such as VKORC1 and CYP2C9, and their concurrent medications. Since various factors impact warfarin’s dose response, numerous mathematical prediction models have been proposed to assist clinicians in finding the optimal initial dose [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18]. The models that only contain clinical variables are known as clinical models (CL); models which contain the patients’ genotype are known as pharmacogenetic models (PKG)

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