Converting the Distinct Heparins Sourced from Bovine or Porcine Mucosa into a Single Anticoagulant Drug

Ana M. F. Tovar; Bruno C. Vairo; Stephan-Nicollas M. C. G. Oliveira; Bianca F. Glauser; Gustavo R. C. Santos; Nina V. Capillé; Adriana A. Piquet; Paloma S. Santana; Kayene V. A. Micheli; Mariana S. Pereira; E. Vilanova; Paulo A. S. Mourão

doi:10.1055/s-0039-1678663

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2019; 119(04): 618-632
DOI: 10.1055/s-0039-1678663

Coagulation and Fibrinolysis

Georg Thieme Verlag KG Stuttgart · New York

Converting the Distinct Heparins Sourced from Bovine or Porcine Mucosa into a Single Anticoagulant Drug

Ana M. F. Tovar^*

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

Bruno C. Vairo^*

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

Stephan-Nicollas M. C. G. Oliveira

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

Bianca F. Glauser

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

Gustavo R. C. Santos

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

Nina V. Capillé

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

Adriana A. Piquet

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

Paloma S. Santana

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

Kayene V. A. Micheli

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

Mariana S. Pereira

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

E. Vilanova

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

,

Paulo A. S. Mourão

¹Institute of Medical Biochemistry Leopoldo de Meis, Universitary Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

› Institutsangaben

Abstract

Unfractionated heparin (UFH) and their low-molecular-weight derivatives are sourced almost exclusively from porcine mucosa (HPI); however, a worldwide introduction of UFH from bovine mucosa (HBI) has been recommended to reinforce the currently unsteady supply chain of heparin products. Although HBI has different chemical composition and about half of the anticoagulant potency of HPI (∼100 and ∼180 international unit [IU]/mg, respectively), they have been employed as interchangeable UFHs in some countries since the 1990s. However, their use as a single drug provoked several bleeding incidents in Brazil, which precipitated the publication of the first monographs exclusive for HBI and HPI by the Brazilian Pharmacopoeia. Nevertheless, we succeed in producing with high-resolution anion-exchange chromatography a novel HBI derivative with anticoagulant potency (200 IU/mg), disaccharide composition (enriched in N,6-disulfated α-glucosamine) and safety profile (bleeding and heparin-induced thrombocytopaenia potentials and protamine neutralization) similar to those seen in the gold standard HPI. Therefore, we show that it is possible to equalize the composition and pharmacological characteristics of these distinct UFHs by employing an easily implementable improvement in the HBI manufacturing.

Keywords

unfractionated heparin - low-molecular-weight heparin - thromboembolism - extracorporeal circulation - bioequivalence

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References
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