title: Higher doses of low-molecular-weight heparin (enoxaparin) are needed to achieve target anti-Xa concentrations in critically ill children*.
abstract: OBJECTIVE
  To demonstrate that low-molecular-weight heparin (enoxaparin) can be used in critically ill pediatric patients to achieve target anti-factor Xa concentrations and determine appropriate dosing corrected for age and illness severity.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Single tertiary level PICU.
  
  
  METHODS
  One hundred ninety-two children age 1 day through 18 years admitted to PICU undergoing every 12-hour enoxaparin therapy with at least one anti-factor Xa concentration obtained. Patients receiving renal replacement therapy or infants with corrected gestational age less than 37 weeks were excluded.
  
  
  METHODS
  None.
  
  
  RESULTS
  We collected patient characteristics including age, weight, height/length, gender, corrected gestational age, illness severity markers, diagnosis, creatinine, enoxaparin dose and times of administration, anti-factor Xa concentrations, and collection times. Only 42% of critically ill children (80 of 192) and only 29% of children (9 of 31) on inotropes achieved recommended target range of anti-factor Xa concentrations on initial recommended enoxaparin dosing (1.5 mg/kg/dose < 2 mo; 1 mg/kg/dose > 2 mo), but 81% were ultimately within target range with dose titration. Increased enoxaparin dose was required to reach target concentrations in younger patients and those with worse illness severity as evidenced by concurrent use of inotropes, previous ICU admission, mechanical ventilation, cardiac surgery, and increased risk of mortality defined by severity-of-illness scores.
  
  
  CONCLUSIONS
  Enoxaparin can be used to reach recommended target range of anti-factor Xa concentrations in the PICU patient. However, younger patients and patients with higher illness severity are less likely to achieve target concentrations using currently recommended dosing and may require higher doses of enoxaparin to reach target anti-factor Xa concentrations. Starting enoxaparin dose at least 1.3 mg/kg dosed every 12 hours for treatment of thromboembolic disease in critically ill patients aged 61 days to 1 year or those requiring inotropic support should be confirmed in prospective study.
authors.affiliation: 1Department of Pediatrics, Division of Critical Care, Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee, WI. 2Department of Pediatrics, Section of Pediatric Critical Care Medicine, Riley Hospital for Children at Indiana University Health and Indiana University School of Medicine, Indianapolis, IN. 3Department of Pediatrics, Division of Quantitative Health Sciences, Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee, WI. 4Department of Pediatrics, Division of Hematology, Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee, WI. 5Blood Center of Wisconsin, Milwaukee, WI. 6Department of Pediatrics, Division of Infectious Disease, Children's Hospital of Wisconsin and Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Schloemer
authors.forename: Samer
authors.initials: S
authors.lastname: Abu-Sultaneh
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Hanson
authors.forename: Ke
authors.initials: K
authors.lastname: Yan
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Hoffmann
authors.forename: Rowena C
authors.initials: RC
authors.lastname: Punzalan
authors.forename: Peter L
authors.initials: PL
authors.lastname: Havens
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D017984:Enoxaparin / Q000008:administration & dosage*; D065427:Factor Xa Inhibitors / Q000097:blood*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012189:Retrospective Studies; D054556:Venous Thromboembolism / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*
chemical_list: D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents