research paper: Clinical use of unfractionated heparin therapy in children: time for change?

Authors

  • Fiona Newall,

    1. Department of Paediatrics, The University of Melbourne
    2. Department of Nursing, The University of Melbourne, Melbourne
    3. Clinical Haematology Department, Royal Children’s Hospital
    4. Murdoch Childrens Research Institute, Parkville, Vic., Australia
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  • Vera Ignjatovic,

    1. Department of Paediatrics, The University of Melbourne
    2. Clinical Haematology Department, Royal Children’s Hospital
    3. Murdoch Childrens Research Institute, Parkville, Vic., Australia
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  • Linda Johnston,

    1. Department of Nursing, The University of Melbourne, Melbourne
    2. School of Nursing and Midwifery, Queens University, Belfast, Ireland
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  • Robyn Summerhayes,

    1. Department of Paediatrics, The University of Melbourne
    2. Clinical Haematology Department, Royal Children’s Hospital
    3. Murdoch Childrens Research Institute, Parkville, Vic., Australia
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  • Geoff Lane,

    1. Department of Cardiology, Royal Children’s Hospital, Parkville, Vic., Australia
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  • Noel Cranswick,

    1. Department of Paediatrics, The University of Melbourne
    2. Australian Paediatric Pharmacology Research Unit (APPRU), Parkville, Vic., Australia
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  • Paul Monagle

    1. Department of Paediatrics, The University of Melbourne
    2. Clinical Haematology Department, Royal Children’s Hospital
    3. Murdoch Childrens Research Institute, Parkville, Vic., Australia
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Fiona Newall, Clinical Haematology Department, Royal Children’s Hospital, Flemington Rd, Parkville Vic., 3052, Australia. E-mail: fiona.newall@rch.org.au

Summary

Paediatric recommendations for unfractionated heparin (UFH) management are extrapolated from adult trials, a practice that may contribute to the inferior UFH-related outcomes in children compared to adults. This is the first study to determine UFH concentration in a population of children and correlated UFH concentration with measures of UFH effect. Correlation coefficients between protamine titration (concentration) and activated partial thromboplastin time (APTT), anti- activated factor X (Xa) assay and thrombin clotting time (effect) were 0·59, 0·46 and 0·52 respectively. A protamine titration level of 0·2–0·4 iu/ml in children was not equivalent to an anti-Xa assay of 0·35–0·7 iu/ml but to an anti-Xa assay 0·17–0·85 iu/ml. In addition, use of the anti-Xa or protamine titration assays to establish an APTT therapeutic range resulted in upper limits of APTT ranges exceeding 200 s. Existing methods for determining therapeutic ranges for UFH in adult populations do not produce equivalent ranges in children. As a result, paediatric clinical guidelines that state a therapeutic range for UFH can be determined using a protamine titration assay of 0·2–0·4 iu/ml or an anti-Xa assay of 0·35–0·7 iu/ml are not based on appropriate evidence. There is an urgent need for change in our approach to the use of UFH in children.

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