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Revisiting the Pharmacology of Unfractionated Heparin

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Abstract

Unfractionated heparin (UFH) is a commonly used anticoagulant therapy for the acute treatment and prevention of thrombosis. Its short duration of action, reversibility of effect by protamine sulfate, and extensive clinical experience are some of the advantages that support its use. However, the choice of dose and dosing regimen of UFH remains challenging for several reasons. First, UFH has a narrow therapeutic window and wide variability in the dose–response relationship. Second, its pharmacodynamic (PD) properties are difficult to characterise owing to the complex multidimensional mechanisms of interaction with the haemostatic system. Third, the complex heterogeneous chemical composition of UFH precludes precise characterisation of its pharmacokinetic (PK) properties. This review provides a comprehensive mechanistic approach to the interaction of UFH with the haemostatic system. The effect of chemical structure on its PK and PD properties is quantitatively described, and a framework for characterisation of the dose–response relationship of UFH for the purpose of dose optimisation is proposed.

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Authors and Affiliations

  1. School of Pharmacy, University of Otago, Dunedin, New Zealand

    Abdallah Derbalah, Stephen Duffull & Hesham Al-Sallami

  2. Department of Nursing, The University of Melbourne, Parkville, VIC, Australia

    Fiona Newall

  3. Department of Paediatrics, The Royal Children’s Hospital, The University of Melbourne, Parkville, VIC, Australia

    Fiona Newall

  4. Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA

    Katie Moynihan

  5. Department of Paediatrics, Harvard Medical School, Boston, MA, USA

    Katie Moynihan

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Abdallah Derbalah, Stephen Duffull, Fiona Newall, Katie Moynihan, and Hesham Al-Sallami declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

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Derbalah, A., Duffull, S., Newall, F. et al. Revisiting the Pharmacology of Unfractionated Heparin. Clin Pharmacokinet 58, 1015–1028 (2019). https://doi.org/10.1007/s40262-019-00751-7

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