title: Hemostatic response in paediatric patients undergoing cardiopulmonary bypass surgery.
abstract: This prospective, single-center cohort study aimed to evaluate the hemostatic response during and after Cardiopulmonary Bypass (CPB) surgery in a large cohort of children up to 6 years of age. Blood samples were drawn at eight time points: post-induction of anesthesia, pre-unfractionated heparin (UFH), post-UFH, post-initiation of bypass, pre-protamine, post-protamine, post-chest-closure, and 6 h post-chest-closure. As expected, all measures of the UFH effect increased significantly post-UFH bolus and decreased post-protamine administration. However, thrombin generation remained inhibited compared to baseline values despite the post-UFH reversal by protamine. We also demonstrate that residual UFH effect is not responsible for the ongoing inhibition of thrombin observed post-protamine administration. The significant increase in both free and total tissue factor pathway inhibitor levels during the CPB surgery might contribute to the persistent thrombin generation/endogenous thrombin potential inhibition post-protamine administration. This study makes a significant and novel contribution by investigating the physiological mechanisms behind the degree of thrombin inhibition by UFH and the residual levels of thrombin inhibition that continue despite protamine reversal and provides a new foundation for future interventional studies in the setting of paediatric CPB surgery.
authors.affiliation: Haematology Research Laboratory, Murdoch Children's Research Institute, Flemington Road, Parkville, Melbourne, VIC 3052, Australia. verai@unimelb.edu.au
authors.forename: Vera
authors.initials: V
authors.lastname: Ignjatovic
authors.forename: Jenny
authors.initials: J
authors.lastname: Than
authors.forename: Robyn
authors.initials: R
authors.lastname: Summerhayes
authors.forename: Fiona
authors.initials: F
authors.lastname: Newall
authors.forename: Stephen
authors.initials: S
authors.lastname: Horton
authors.forename: Andrew
authors.initials: A
authors.lastname: Cochrane
authors.forename: Paul
authors.initials: P
authors.lastname: Monagle
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage; D001780:Blood Coagulation Tests; D016063:Blood Loss, Surgical / Q000503:physiopathology*; D002315:Cardiopulmonary Bypass; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000601:surgery*; D006487:Hemostasis / Q000187:drug effects / Q000502:physiology*; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008074:Lipoproteins / Q000097:blood; D008297:Male; D011446:Prospective Studies; D011479:Protamines / Q000008:administration & dosage; D013917:Thrombin / Q000378:metabolism; D014739:Victoria
chemical_list: D000925:Anticoagulants; D008074:Lipoproteins; D011479:Protamines; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin; D013917:Thrombin