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

Fiona Newall; Vera Ignjatovic; Linda Johnston; Robyn Summerhayes; Geoff Lane; Noel Cranswick; Paul Monagle

doi:10.1160/TH09-09-0624

Thrombosis and Haemostasis, Table of Contents

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

¹Department of Paediatrics, The University of Melbourne, Melbourne, Australia

²Department of Nursing, The University of Melbourne, Melbourne, Australia

³Clinical Haematology Department, Royal Children’s Hospital, Melbourne, Australia

⁴Murdoch Childrens Research Institute, Parkville, Australia

,

Vera Ignjatovic

¹Department of Paediatrics, The University of Melbourne, Melbourne, Australia

³Clinical Haematology Department, Royal Children’s Hospital, Melbourne, Australia

⁴Murdoch Childrens Research Institute, Parkville, Australia

,

Linda Johnston

²Department of Nursing, The University of Melbourne, Melbourne, Australia

⁵School of Nursing and Midwifery, Queens University, Belfast, UK

,

Robyn Summerhayes

¹Department of Paediatrics, The University of Melbourne, Melbourne, Australia

³Clinical Haematology Department, Royal Children’s Hospital, Melbourne, Australia

⁴Murdoch Childrens Research Institute, Parkville, Australia

,

Geoff Lane

⁶Department of Cardiology, Royal Children’s HospitalMelbourne, Australia

,

Noel Cranswick

¹Department of Paediatrics, The University of Melbourne, Melbourne, Australia

⁷Australian Paediatric Pharmacology Research Unit (APPRU), Royal Children’s Hospital, Melbourne, Australia

,

Paul Monagle

¹Department of Paediatrics, The University of Melbourne, Melbourne, Australia

³Clinical Haematology Department, Royal Children’s Hospital, Melbourne, Australia

⁴Murdoch Childrens Research Institute, Parkville, Australia

› Author Affiliations

Abstract

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.

Keywords

Unfractionated heparin - anticoagulant activity - age-related response

Full Text

References

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