title: Age is a determinant factor for measures of concentration and effect in children requiring unfractionated heparin.
abstract: Previous studies investigating continuous unfractionated heparin (UFH) therapy report age-related differences in UFH response in children, as measured by APTT and anti-Xa assay. This study determined the age-related response following administration of a single UFH bolus of 75-100 IU/kg in children. Venous blood samples were collected from children (n=56) at 15, 30, 45 and 120 minutes post-UFH. Anti-Xa, anti-IIa, APTT, TCT and protamine titration were performed on all samples. Age-dependent differences in the effect and concentration of UFH were identified for the anti-Xa, anti-IIa and protamine titration assays, respectively. In addition, a trend suggesting a proportional increase in anti-Xa and anti-IIa-mediated UFH effect with age was evident. Logistic regression demonstrated an increase in protamine titration of 0.6 IU/ml for every year of age in samples collected 15 minutes post-UFH. UFH-mediated anti-IIa activity was reduced compared to anti-Xa activity across childhood, with a two-fold increase in anti-Xa to anti-IIa ratio in infants less than one year of age compared to teenagers in the setting of high UFH concentrations. This study demonstrates that the previously reported age-dependent response to UFH occurs in the context of an age-dependent serum concentration of UFH. The trend toward increased UFH serum concentration and anticoagulant activity with age may be related to short-term differences in UFH binding to coagulant and competitive plasma proteins in vivo.
authors.affiliation: Department of Paediatrics, The University of Melbourne, Melbourne, 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; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D054796:Drug Dosage Calculations; D019317:Evidence-Based Medicine; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010314:Partial Thromboplastin Time / Q000379:methods; D017410:Practice Guidelines as Topic; D012016:Reference Values
chemical_list: D006493:Heparin; D015951:Factor Xa