title: Unfractionated heparin dosing in young infants: clinical outcomes in a cohort monitored with anti-factor Xa levels.
abstract: BACKGROUND
  Unfractionated heparin (UFH) is a widely used anticoagulant. Current American College of Chest Physicians guidelines for infants extrapolated from adults recommend 28 U kg(-1) h(1) of UFH to achieve an anti-factor Xa level of 0.35-0.7 IU mL(-1).
  
  
  OBJECTIVE
  To assess the profile of anti-FXa-based UFH dosing guidelines in infants.
  
  
  METHODS
  We included all infants aged < 6 months treated with per-protocol intravenous UFH at the Hospital for Sick Children, Toronto, over a 3.5-year period.
  
  
  RESULTS
  Of 100 infants, 11% achieved sustained therapeutic anti-FXa levels with current dose recommendations. Only 15% achieved target anti-FXa levels within 24 h with per-protocol dose escalations. Seventeen per cent of patients never achieved therapeutic anti-FXa levels, despite up to 60 days of therapy and triple the recommended dose. The median dose needed to achieve therapeutic anti-FXa levels in the remaining 83 infants was 33 U kg(-1) h(-1) (interquartile range, 30-36). Two in three infants had decreased thrombus size at completion of therapy and no thrombus progression/recurrence, and 11/100 infants suffered major bleeding. Without exclusion of extracorporeal membrane oxygenation patients, an activated partial thromboplastin time (APTT) of > 180 s was detected as a risk factor for major bleeding.
  
  
  CONCLUSIONS
  UFH monitoring is challenging in infants. Despite their delay in reaching therapeutic anti-FXa levels, infants monitored with the adult-based anti-FXa range have a high thrombus resolution rate, no thrombus progression, but a relatively high bleeding rate. Extreme APTT elevation may contribute to this bleeding risk, particularly in critically ill patients. Current UFH guidelines for young infants may still be inadequate, and laboratory methods with age-appropriate ranges may be required to further improve clinical outcomes within this population.
authors.affiliation: Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. tal.schechter-finkelstein@sickkids.ca
authors.forename: T
authors.initials: T
authors.lastname: Schechter
authors.forename: Y
authors.initials: Y
authors.lastname: Finkelstein
authors.forename: M
authors.initials: M
authors.lastname: Ali
authors.forename: W H
authors.initials: WH
authors.lastname: Kahr
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: A K
authors.initials: AK
authors.lastname: Chan
authors.forename: G
authors.initials: G
authors.lastname: Deveber
authors.forename: L R
authors.initials: LR
authors.lastname: Brandão
mesh_terms: D000367:Age Factors; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D016009:Chi-Square Distribution; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods*; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D009864:Ontario; D010314:Partial Thromboplastin Time; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D006493:Heparin