Optimal pediatric dosing of unfractionated heparin (UFH) is challenging due to paucity of clinical outcome and pharmacokinetic-pharmacodynamic (PK/PD) studies in pediatrics. This study aimed to: (i) develop a PK/PD model for UFH, quantified by anti-factor Xa assay and the UFH effect measured by activated partial thromboplastin time (aPTT) (ii) evaluate pediatric UFH infusions in achieving anti-factor Xa (0.3 – 0.7 IU/mL) therapeutic target by simulations. Electronic health record data were retrospectively collected from 633 patients < 19 years old admitted to Texas Children's Hospital. The PK/PD model was developed using a 70% (training)-30% (test) data split approach. A one-compartment PK model with linear elimination adequately described the UFH PK. An allometrically scaled body weight on clearance (CL) and volume of distribution (Vd) with an age-dependent maturation function of extracellular water on Vd were the covariates identified. Comparable with literature, the typical values for CL and Vd were 3.28 L/(hr·50 kg) and 8.83 L/50 kg, respectively. A linear model adequately described the UFH-aPTT relationship with an estimated slope of 150. Simulations of the currently recommended starting infusions (28 IU/hr/kg for pediatrics < 1 year old or 20 IU/hr/kg for pediatrics > 1 year old) showed that anti-factor Xa therapeutic target was achieved only in 15.3%, 14.6%, 36.9% and 45.11% of subjects in the age groups of < 1 year, 1-6 years, 6-12 years, and 12-19 years, respectively. In conclusion, the UFH anti-factor Xa target is not achieved initially especially in young pediatrics, suggesting the need to optimize UFH dosing to achieve higher therapeutic success.

This article is protected by copyright. All rights reserved