Related Experiment Video
Updated: Jan 6, 2026
23:33
The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation
Published on: February 28, 2012
84.3K
Personalised Warfarin Dosing in Children Post-cardiac Surgery
Basma Zuheir Al-Metwali1,2,3, Peter Rivers1, Larry Goodyer1
1School of Pharmacy, De Montfort University, Leicester, UK.
Pediatric Cardiology
|October 7, 2019
Summary
A new warfarin dosing algorithm improved anticoagulation control in children, especially during initial treatment. This personalized approach, using genetic information, showed faster stabilization and better time in therapeutic range compared to standard methods.
Area of Science:
- Pharmacology
- Pediatric Cardiology
- Genetics
Background:
- Warfarin dosing presents challenges due to individual pharmacokinetic (PK) and pharmacodynamic (PD) variations.
- Genetic factors, including CYP2C9 and VKORC1 genotypes, significantly influence warfarin metabolism and response.
- Optimizing warfarin therapy in children, particularly post-cardiac surgery, is crucial for effective anticoagulation.
Purpose of the Study:
- To evaluate a novel, personalized warfarin dosing algorithm for children based on a PK/PD model incorporating genetic data.
- To compare the efficacy of the model-based dosing algorithm against conventional weight-based dosing in pediatric patients.
Main Methods:
- A prospective, observational study involving two groups of children post-cardiac surgery.
- Group 1: Warfarin-naïve patients received model-estimated loading and maintenance doses, compared to historical controls.
- Group 2: Patients on maintenance therapy underwent a crossover study comparing model-based versus conventional dosing.
Main Results:
- In Group 1, model-based dosing led to a shorter time to stable anticoagulation (29.0 vs. 96.5 days) and a higher percentage of time in therapeutic range (83.4% vs. 62.3%).
- Group 1 also showed a longer time to first therapeutic INR (5 vs. 2 days) and over-anticoagulation (15.0 vs. 4.0 days) compared to controls.
- No significant differences in INR control were observed between model-based and conventional dosing in Group 2 (mean %ITR 68.82% vs. 67.9%; mean %TTR 85.47% vs. 80.2%).
Conclusions:
- Model-based warfarin dosing, incorporating genetic information, shows potential to enhance anticoagulation control in pediatric patients, particularly during initiation and stabilization.
- Further larger-scale studies are warranted to validate these findings and confirm the benefits of personalized warfarin dosing algorithms in children.
- The study highlights the need for advanced dosing strategies to overcome warfarin's complex PK/PD profile in pediatric populations.
Related Concept Videos
01:29Drug Dosing: Infants and Children
226
Pediatric patient dosages diverge from adults due to disparities in body surface area, total body water, and extracellular fluid per kilogram of body weight. The dosing regimen considers the variations in pharmacokinetics and pharmacology across distinct age groups, encompassing preterm newborns, infants, young children, older children, and adolescents. Calculation of pediatric patient doses is predicated on determining body surface area, which exhibits a superior correlation with the child's...
226
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
188
In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
188
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution
231
Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight,...
231
01:15Drug Dosing: Geriatric Patients
199
Elderly individuals encompass a diverse population with varying degrees of age-related physiological changes. Defining the elderly presents challenges, as the geriatric population is often arbitrarily categorized as individuals older than 65. However, many individuals in this group lead active and healthy lives, with an increasing number surpassing 85 years and falling into the older elderly category. Physiological changes associated with aging impact performance capacity and homeostatic...
199
01:29Venous Thrombosis III: Interprofessional Care
254
Venous thrombosis requires effective prevention and treatment strategies to improve patient outcomes and reduce potential complications.Prevention StrategiesHealthcare providers must prioritize preventing venous thromboembolism (VTE) for all adult patients upon admission. Interventions depend on bleeding and thrombosis risk, medical history, current medications, diagnoses, planned procedures, and patient preferences. Patients on bed rest should change positions every two hours and, if not...
254
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
2.0K
Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
2.0K