title: Lack of anti-factor Xa assay standardization results in significant low molecular weight heparin (enoxaparin) dose variation in neonates and children.
abstract: BACKGROUND
  Enoxaparin is a frequently used anticoagulant in children. Unlike in adults, consensus guidelines recommend therapeutic monitoring to a target anti-factor Xa level of 0.5-1 U mL(-1) . Therapeutic ranges are not well correlated with clinical outcomes (e.g. thrombosis or hemorrhage), and assays are not standardized. Owing to limited reagent supplies, our clinical laboratory conducted a validation process and switched anti-FXa assays. Although the assays correlated well with each other, anti-FXa values were, on average, 33% higher with the new assay. The target anti-FXa range was not altered. We evaluated how this change in anti-FXa assays influenced enoxaparin dosing (mg kg(-1) ).
  
  
  METHODS
  Enoxaparin dosing and anti-FXa values for all patients started on enoxaparin for the 6 months before and after assay change were retrospectively compiled and analyzed with a Student's t-test.
  
  
  RESULTS
  One hundred and nine children were started on enoxaparin before assay change, and 104 after assay change. The mean therapeutic enoxaparin dose (mg kg(-1) ) was significantly lower in subjects aged < 3 months (P = 0.01) and 3 months to 2 years (P < 0.0001), but not in subjects aged > 2 years (P = 0.18), after assay change. The median number of enoxaparin dose changes required to achieve the target range was significantly reduced after assay change, from 1 to 0 (P = 0.004).
  
  
  CONCLUSIONS
  The current pediatric practice of dose adjustment to achieve and maintain a target anti-FXa range is vulnerable to assay determination, which may provide false reassurance of efficacy and safety and represent misappropriation of time and resources. These data support a pediatric randomized controlled clinical trial comparing the safety and efficacy of enoxaparin weight-based dosing with or without dose titration based on anti-FXa.
authors.affiliation: Divisions of Hematology and Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Greene
authors.forename: C
authors.initials: C
authors.lastname: Law
authors.forename: M
authors.initials: M
authors.lastname: Jung
authors.forename: S
authors.initials: S
authors.lastname: Walton
authors.forename: V
authors.initials: V
authors.lastname: Ignjatovic
authors.forename: P
authors.initials: P
authors.lastname: Monagle
authors.forename: L J
authors.initials: LJ
authors.lastname: Raffini
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage*; D002675:Child, Preschool; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D017984:Enoxaparin / Q000737:chemistry*; D015951:Factor Xa / Q000008:administration & dosage*; D065427:Factor Xa Inhibitors / Q000008:administration & dosage*; D006403:Hematologic Tests / Q000379:methods*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015203:Reproducibility of Results; D012189:Retrospective Studies
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D015951:Factor Xa
keywords: anticoagulants; drug monitoring; enoxaparin; infant; pediatrics; thrombosis