title: Monitoring unfractionated heparin in children: a parallel-cohort randomized controlled trial comparing 2 dose protocols.
abstract: Monitoring unfractionated heparin (UFH) is crucial to prevent over- or under-anticoagulation. However, the optimal parameters for monitoring UFH in children are not well established. The study objectives were to investigate (1) the relationship between UFH dose and its anticoagulant effect as assessed by anti-Xa, activated partial thromboplastin time (aPTT) and activated clotting time (ACT); (2) other factors influencing UFH effect; (3) the agreement between the assays; and (4) the association between UFH effect and clinical outcome. HEARTCAT was a parallel-cohort randomized controlled trial comparing high-dose (100 U/kg bolus followed by age-based continuous infusion in randomized children) vs low-dose UFH (50 U/kg bolus) during cardiac catheterization in children. Blood samples were drawn before and after UFH administration at 30, 60, and 90 minutes. Four-hundred and two samples of 149 patients were evaluable. Anti-Xa, aPTT, and ACT all showed good discrimination between UFH doses. Regression models demonstrated the following determinants of UFH effect: UFH dose, age, baseline antithrombin (for anti-Xa), and baseline levels of aPTT and ACT, respectively. UFH effects were lower in infants compared with older children, which was more pronounced at low-dose than at high-dose UFH. Agreement between the 3 assays was poor. Most aPTT values were above therapeutic range or beyond measuring limit and thus of limited value for UFH monitoring. No association of UFH dose or effect with clinical outcome could be observed. In conclusion, all assays reflected a significant UFH dose-effect relationship, however, with poor agreement between the respective tests. The age-dependency of UFH effect was confirmed. Notably, the influence of age on UFH effect was dose-dependent.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria;
authors.forename: Andreas
authors.initials: A
authors.lastname: Hanslik
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria;
authors.forename: Erwin
authors.initials: E
authors.lastname: Kitzmüller
authors.affiliation: School of Psychology, University of Vienna, Austria; and.
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Tran
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria;
authors.forename: Katharina
authors.initials: K
authors.lastname: Thom
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria;
authors.forename: Hratsch
authors.initials: H
authors.lastname: Karapetian
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria;
authors.forename: Nicole
authors.initials: N
authors.lastname: Prutsch
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria;
authors.forename: Jasmin
authors.initials: J
authors.lastname: Voitl
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria;
authors.forename: Ina
authors.initials: I
authors.lastname: Michel-Behnke
authors.affiliation: Nursing Research, Royal Children's Hospital, Melbourne, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: Newall
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria;
authors.forename: Christoph
authors.initials: C
authors.lastname: Male
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D008297:Male; D010314:Partial Thromboplastin Time
chemical_list: D000925:Anticoagulants; D006493:Heparin