title: Higher Tinzaparin Dosing Is Needed to Achieve Target Anti-Xa Levels in Pediatric Cardiac Intensive Care Patients.
abstract: OBJECTIVE
  This study was conducted to evaluate tinzaparin dosing and therapeutic drug monitoring.
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Single tertiary-level PICU.
  
  
  METHODS
  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.
  
  
  METHODS
  None.
  
  
  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.
authors.affiliation: 1Department of Pediatric Intensive Care, Leiden University Medical Center, Leiden, the Netherlands. 2Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands. 3Department of Pediatric Hematology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Roeleveld
authors.forename: Alieke
authors.initials: A
authors.lastname: van der Hoeven
authors.forename: Rob B P
authors.initials: RB
authors.lastname: de Wilde
authors.forename: Jeroen
authors.initials: J
authors.lastname: Eikenboom
authors.forename: Frans J
authors.initials: FJ
authors.lastname: Smiers
authors.forename: Heleen E
authors.initials: HE
authors.lastname: Bunker-Wiersma
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000097:blood*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric; D008297:Male; D012189:Retrospective Studies; D000078222:Tinzaparin
chemical_list: D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D000078222:Tinzaparin