title: Clinical use of unfractionated heparin therapy in children: time for change?
abstract: Paediatric recommendations for unfractionated heparin (UFH) management are extrapolated from adult trials, a practice that may contribute to the inferior UFH-related outcomes in children compared to adults. This is the first study to determine UFH concentration in a population of children and correlated UFH concentration with measures of UFH effect. Correlation coefficients between protamine titration (concentration) and activated partial thromboplastin time (APTT), anti- activated factor X (Xa) assay and thrombin clotting time (effect) were 0·59, 0·46 and 0·52 respectively. A protamine titration level of 0·2-0·4 iu/ml in children was not equivalent to an anti-Xa assay of 0·35-0·7 iu/ml but to an anti-Xa assay 0·17-0·85 iu/ml. In addition, use of the anti-Xa or protamine titration assays to establish an APTT therapeutic range resulted in upper limits of APTT ranges exceeding 200 s. Existing methods for determining therapeutic ranges for UFH in adult populations do not produce equivalent ranges in children. As a result, paediatric clinical guidelines that state a therapeutic range for UFH can be determined using a protamine titration assay of 0·2–0·4 iu/ml or an anti-Xa assay of 0·35-0·7 iu/ml are not based on appropriate evidence. There is an urgent need for change in our approach to the use of UFH in children.
authors.affiliation: Department of Paediatrics, The University of Melbourne, Parkville, Vic., Australia. fiona.newall@rch.org.au
authors.forename: Fiona
authors.initials: F
authors.lastname: Newall
authors.forename: Vera
authors.initials: V
authors.lastname: Ignjatovic
authors.forename: Linda
authors.initials: L
authors.lastname: Johnston
authors.forename: Robyn
authors.initials: R
authors.lastname: Summerhayes
authors.forename: Geoff
authors.initials: G
authors.lastname: Lane
authors.forename: Noel
authors.initials: N
authors.lastname: Cranswick
authors.forename: Paul
authors.initials: P
authors.lastname: Monagle
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000925:Anticoagulants / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D001780:Blood Coagulation Tests / Q000379:methods; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D015951:Factor Xa / Q000276:immunology; D005260:Female; D006493:Heparin / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D010314:Partial Thromboplastin Time
chemical_list: D000925:Anticoagulants; D006493:Heparin; D015951:Factor Xa