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CC BY 4.0 · TH Open 2024; 08(03): e297-e307
DOI: 10.1055/a-2359-0987
Review Article

Management of Therapeutic-intensity Unfractionated Heparin: A Narrative Review on Critical Points

Isabelle Gouin-Thibault
1   Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, France
2   IRSET-INSERM-1085, Univ Rennes, Rennes, France
,
Alexandre Mansour
2   IRSET-INSERM-1085, Univ Rennes, Rennes, France
3   Department of Anesthesia and Critical Care, Pontchaillou University Hospital of Rennes, France
,
Michael Hardy
4   Department of Biology, Université Catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center, Namur Research Institute for Life Sciences, Hematology Laboratory, Yvoir, Belgium
5   Department of Anesthesiology, Université catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center, Namur Research Institute for Life Sciences, Yvoir, Belgium
,
Pierre Guéret
1   Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, France
,
Emmanuel de Maistre
6   Division of Laboratory Hematology, University Hospital of Dijon Bourgogne, Dijon, France
,
Virginie Siguret 
7   AP-HP, Department of Laboratory Hematology, University Hospital of Lariboisière, INSERM UMRS-1140, Paris Cité University, Paris, France
,
Adam Cuker
8   Department of Medicine and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
,
François Mullier
4   Department of Biology, Université Catholique de Louvain, CHU UCL Namur, Namur Thrombosis and Hemostasis Center, Namur Research Institute for Life Sciences, Hematology Laboratory, Yvoir, Belgium
9   Department of Biology, Université Catholique de Louvain, Institut de Recherche Expérimentale et Clinique—Pôle Mont, Namur, Belgium
,
Thomas Lecompte
1   Department of Laboratory Hematology, Pontchaillou University Hospital of Rennes, France
6   Division of Laboratory Hematology, University Hospital of Dijon Bourgogne, Dijon, France
9   Department of Biology, Université Catholique de Louvain, Institut de Recherche Expérimentale et Clinique—Pôle Mont, Namur, Belgium
10   Department of Pharmacy, Namur Thrombosis and Hemostasis Center, Namur Research Institute for Life Sciences, University of Namur, Namur, Belgium
11   Division of Vascular Medicine, University Hospital of Nancy, University of Lorraine, Nancy, France
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Abstract

Nowadays, unfractionated heparin (UFH) use is limited to selected patient groups at high risk of both bleeding and thrombosis (patients in cardiac surgery, in intensive care unit, and patients with severe renal impairment), rendering its management extremely challenging, with many unresolved questions despite decades of use.

In this narrative review, we revisit the fundamental concepts of therapeutic anticoagulation with UFH and address five key points, summarizing controversies underlying the use of UFH and discussing the few recent advances in the field: (1) laboratory tests for UFH monitoring have significant limitations; (2) therapeutic ranges are not well grounded; (3) the actual influence of antithrombin levels on UFH's anticoagulant activity is not well established; (4) the concept of UFH resistance lacks supporting data; (5) scarce data are available on UFH use beyond acute venous thromboembolism.

We therefore identified key issues to be appropriately addressed in future clinical research: (1) while anti-Xa assays are often considered as the preferred option, we call for a vigorous action to improve understanding of the differences between types of anti-Xa assays and to solve the issue of the usefulness of added dextran; (2) therapeutic ranges for UFH, which were defined decades ago using reagents no longer available, have not been properly validated and need to be confirmed or reestablished; (3) UFH dose adjustment nomograms require full validation.

Keywords

heparin - aPTT - anti-Xa - antithrombin - nomogram - drug resistance

Author Contributions

I.G.T., F.M., and T.L. did the literature research, and I.G.T. and T.L. wrote the first draft. A.M. designed the figure. All authors performed critical revision, reviewed the manuscript, and approved the submitted version.




Publication History

Received: 11 December 2023

Accepted: 25 June 2024

Accepted Manuscript online:
27 September 2024

Article published online:
17 October 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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