title: Novel interactions between UFH and TFPI in children.
abstract: The impact of age upon therapeutic response to unfractionated heparin (UFH) in children is proposed to reflect quantitative and potentially qualitative differences in coagulation proteins across childhood. This study explores the UFH-dependent tissue factor pathway inhibitor (TFPI) release in children compared to previously published data in adults. Children <16 years of age undergoing cardiac angiography formed the population for this prospective cohort study. TFPI release was measured prior to (baseline) and at 15, 30, 45 and 120 min post-UFH dose. This study demonstrated that, whilst the immediate release of TFPI post-UFH was similar in children compared to adults, TFPI release in children remained increased and consistent for a significantly longer period post-UFH administration compared to adults. Plasma TFPI levels in children did not demonstrate an UFH concentration -dependent reduction, as has been previously reported in adults. The prolonged TFPI-mediated anticoagulant levels observed in children administered UFH may contribute to the increased rate of major bleeding reported in children compared to adults. Furthermore, we postulate that this sustained UFH-dependent increase in TFPI levels in children may influence the binding of UFH to competitive plasma proteins, such as those involved in the immunological response to UFH associated with heparin-induced thrombocytopenia.
authors.affiliation: Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia. fiona.newall@rch.org.au
authors.forename: Fiona
authors.initials: F
authors.lastname: Newall
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
authors.forename: Vera
authors.initials: V
authors.lastname: Ignjatovic
mesh_terms: D000293:Adolescent; D000375:Aging / Q000097:blood; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D011446:Prospective Studies; D011479:Protamines / Q000097:blood
chemical_list: D000925:Anticoagulants; D008074:Lipoproteins; D011479:Protamines; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin