Higher Tinzaparin Dosing Is Needed to Achieve Target Anti-Xa Levels in Pediatric Cardiac Intensive Care Patients

作者：Roeleveld Peter P^*; van der Hoeven Alieke; de Wilde Rob B P; Eikenboom Jeroen; Smiers Frans J; Bunker Wiersma Heleen E

来源：Pediatric Critical Care Medicine, 2016, 17(3): 203-209.

DOI：10.1097/PCC.0000000000000640

• anti-Xa
• child
• pediatric intensive care
• pharmacokinetics
• low-molecular weight heparin
• tinzaparin

Objectives: This study was conducted to evaluate tinzaparin dosing and therapeutic drug monitoring.
Design: Retrospective study.
Setting: Single tertiary-level PICU.
Patients: Tinzaparin doses and anti-Xa levels from all children admitted to a PICU (from October 1, 2010, to December 31, 2013) were retrospectively analyzed. Thirty-nine children, median age of 13 months (interquartile range, 73 mo), with 46 episodes of newly started therapeutic tinzaparin were identified.
Interventions: None.
Measurements and Main Results: Local hospital policy is to determine the first anti-Xa level after 3-4 doses, 4 hours post dose, targeting 0.5-1.0 IU/mL for therapeutic dosing. First anti-Xa levels were determined after 3.8 ( 2.4; range, 1-14) doses and were below the target range in 37 of 46 episodes (76%) of tinzaparin use: mean, 0.30 (+/- 0.11) IU/mL. Tinzaparin was then increased by 23% (+/- 19) in 23 of 37 episodes (62%), and further anti-Xa levels were determined. In 14 episodes, further levels were not available because of cessation of tinzaparin therapy. Target anti-Xa levels, 0.69 (+/- 0.24) IU/mL, were eventually reached in the PICU in 22 patients after a mean of 8.8 (+/- 7.3) doses. In the entire cohort, the dose required to achieve target anti-Xa levels was significantly higher (+51 [+/- 62] U/kg; p = 0.003) than the recommended starting dose.
Conclusions: Target anti-Xa levels were reached with tinzaparin dosing in PICU patients after more than 8 doses, warranting further dose-effect research. Especially in the younger age group, substantially higher dose requirements than proposed in the internationally used guidelines are required. With the results of our study, we suggest a different therapeutic drug monitoring approach than that currently used.

• 出版日期2016-3