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Reassessing the Pediatric Dosing Recommendations for Unfractionated Heparin Using Real-World Data: A

Ahmed M Salem1, Tao Niu2, Chao Li3

  • 1Center for Translational Medicine, Department of Pharmacy Practice, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.

Journal of Clinical Pharmacology
|November 24, 2021
PubMed

Insights

Optimal pediatric dosing of unfractionated heparin (UFH) is challenging. Current UFH infusions do not consistently achieve therapeutic anti-factor Xa targets in children, particularly younger ones, indicating a need for optimized dosing strategies.

Area of Science:

  • Pharmacology
  • Pediatric Medicine
  • Clinical Pharmacy

Background:

  • Pediatric dosing of unfractionated heparin (UFH) lacks robust pharmacokinetic-pharmacodynamic (PK/PD) data and clinical outcome studies.
  • Achieving therapeutic targets for UFH in pediatric patients remains a significant clinical challenge.

Purpose of the Study:

  • To develop a PK/PD model for UFH in pediatric patients using anti-factor Xa and activated partial thromboplastin time (aPTT).
  • To simulate pediatric UFH infusion regimens to assess the achievement of the anti-factor Xa therapeutic target (0.3-0.7 IU/mL).

Main Methods:

  • Retrospective analysis of electronic health record data from 633 pediatric patients (<19 years).
  • Development of a PK/PD model using a 70% training/30% testing split-sample approach.
  • Allometric scaling for body weight on clearance (CL) and volume of distribution (Vd), with age-dependent maturation for Vd, were identified covariates.

Main Results:

  • A 1-compartment PK model with linear elimination adequately described UFH PK.
  • The UFH-aPTT relationship was linear, with an estimated slope of 150 seconds/(IU/mL).
  • Simulations revealed that current recommended UFH starting infusions achieved the anti-factor Xa target in only 15.3% (<1 year), 14.6% (1-6 years), 36.9% (6-12 years), and 45.11% (12-19 years) of patients.

Conclusions:

  • Current UFH dosing regimens are insufficient to achieve target anti-factor Xa levels in pediatric patients, especially in younger age groups.
  • There is a critical need to optimize UFH dosing strategies in pediatrics to improve therapeutic efficacy and patient outcomes.

Keywords:
UFHaPTTanti-factor Xapediatricspopulation PK/PD

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