Thromb Haemost 2010; 103(05): 1085-1090
DOI: 10.1160/TH09-09-0624
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Age is a determinant factor for measures of concentration and effect in children requiring unfractionated heparin

Fiona Newall
1   Department of Paediatrics, The University of Melbourne, Melbourne, Australia
2   Department of Nursing, The University of Melbourne, Melbourne, Australia
3   Clinical Haematology Department, Royal Children’s Hospital, Melbourne, Australia
4   Murdoch Childrens Research Institute, Parkville, Australia
,
Vera Ignjatovic
1   Department of Paediatrics, The University of Melbourne, Melbourne, Australia
3   Clinical Haematology Department, Royal Children’s Hospital, Melbourne, Australia
4   Murdoch Childrens Research Institute, Parkville, Australia
,
Linda Johnston
2   Department of Nursing, The University of Melbourne, Melbourne, Australia
5   School of Nursing and Midwifery, Queens University, Belfast, UK
,
Robyn Summerhayes
1   Department of Paediatrics, The University of Melbourne, Melbourne, Australia
3   Clinical Haematology Department, Royal Children’s Hospital, Melbourne, Australia
4   Murdoch Childrens Research Institute, Parkville, Australia
,
Geoff Lane
6   Department of Cardiology, Royal Children’s HospitalMelbourne, Australia
,
Noel Cranswick
1   Department of Paediatrics, The University of Melbourne, Melbourne, Australia
7   Australian Paediatric Pharmacology Research Unit (APPRU), Royal Children’s Hospital, Melbourne, Australia
,
Paul Monagle
1   Department of Paediatrics, The University of Melbourne, Melbourne, Australia
3   Clinical Haematology Department, Royal Children’s Hospital, Melbourne, Australia
4   Murdoch Childrens Research Institute, Parkville, Australia
› Author Affiliations
Further Information

Publication History

Received: 06 September 2009

Accepted after major revision: 05 January 2010

Publication Date:
22 November 2017 (online)

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Summary

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 as-says, 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.