title: In vivo age dependency of unfractionated heparin in infants and children.
abstract: BACKGROUND
  Unfractionated Heparin (UFH) is used widely in paediatrics. Paediatric specific recommendations for UFH therapy are few, with the majority of recommendations being extrapolated from adult practice. In vitro studies have shown that this practice may be suboptimal. This study aimed to improve the understanding of the impact of age upon UFH response in vivo.
  
  
  METHODS
  This prospective, observational study, conducted in the Paediatric Intensive Care Unit (PICU), included: patients 16 years or younger; treated with UFH of at least 10 U/Kg/hr. Laboratory analysis included: Antithrombin, APTT, Anti-Xa, Anti-IIa and thrombin generation expressed as the Endogenous Thrombin Potential. Results were grouped according to patient age (i.e. <1, 1-5, 6-10 and 11-16 years).
  
  
  RESULTS
  85 patients received an equivalent mean UFH dose with a median duration of 3 days. Antithrombin levels were decreased compared to age-related norms in children up to 11 years of age. APTT results were comparable across the age-groups. The Anti-Xa results using two different assays showed a trend for lower values in younger children. All children less than one year old recorded Anti-Xa values outside the therapeutic range for heparin therapy, for both assays. There was a trend for decreased Anti-IIa activity in younger children. Endogenous Thrombin Potential showed a significant trend for increased inhibition in older children. In vitro Antithrombin supplementation did not change the Anti-Xa or thrombin generation.
  
  
  CONCLUSIONS
  This study confirms that, in vivo, for the same dose of UFH, the anti Xa and anti IIa effect, as well as the inhibition of endogenous thrombin potential is age dependent and that these differences are not purely AT dependent. The implication is that the anticoagulant and antithrombotic effect of a given dose of UFH differs with age. Clinical outcome studies to determine the optimal dosing for each age group are warranted.
authors.affiliation: Department of Pathology, The University of Melbourne, Parkville, VIC 3010. 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: Robyn
authors.initials: R
authors.lastname: Summerhayes
authors.forename: Andrew
authors.initials: A
authors.lastname: Gan
authors.forename: Warwick
authors.initials: W
authors.lastname: Butt
authors.forename: Linda
authors.initials: L
authors.lastname: Johnston
authors.forename: Paul
authors.initials: P
authors.lastname: Monagle
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III / Q000032:analysis; D000991:Antithrombins / Q000032:analysis / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D008297:Male; D010314:Partial Thromboplastin Time; D011446:Prospective Studies; D011516:Prothrombin / Q000037:antagonists & inhibitors; D013917:Thrombin / Q000032:analysis
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D000990:Antithrombin III; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D013917:Thrombin