Anticoagulant Activity of Heparins from Different Animal Sources are Driven by a Synergistic Combination of Physical-chemical Factors

Stephan N.M.C.G. Oliveira; Ana M.F. Tovar; Francisco F. Bezerra; Adriana A. Piquet; Nina V. Capillé; Paloma S. Santos; Eduardo Vilanova; Paulo A.S. Mourão

doi:10.1055/a-1946-0325

TH Open, Table of Contents

CC BY 4.0 · TH Open 2022; 06(04): e309-e322
DOI: 10.1055/a-1946-0325

Original Article

Anticoagulant Activity of Heparins from Different Animal Sources are Driven by a Synergistic Combination of Physical-chemical Factors

Stephan N.M.C.G. Oliveira

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Ana M.F. Tovar

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Francisco F. Bezerra

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Adriana A. Piquet

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Nina V. Capillé

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Paloma S. Santos

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Eduardo Vilanova

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Paulo A.S. Mourão

¹Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

› Author Affiliations

Abstract

Heparin has already been found in a variety of animal tissues but only few of them became effective sources for production of pharmaceutical preparations. Here, we correlate physical-chemical features and anticoagulant activities of structurally similar heparins employed in the past (from bovine lung, HBL), in the present (from porcine intestine, HPI) and in development for future use (from ovine intestine, HOI). Although they indeed have similar composition, our physical-chemical analyses with different chromatography and spectrometric techniques show that both HOI and HBL have molecular size notably lower than HPI and that the proportions of some of their minor saccharide components can vary substantially. Measurements of anticoagulant activities with anti-FIIa and anti-FXa assays confirmed that HPI and HOI have potency similar each other but significantly higher than HBL. Such a lower activity of HBL has been attributed to its reduced molecular size. Considering that HOI also has reduced molecular size, we find that its increased anticoagulant potency might result from an improved affinity to antithrombin (three times higher than HBL) promoted by the high content of N,3,6-trisulfated glucosamine units, which in turn are directly involved in the heparin-antithrombin binding. Therefore, the anticoagulant activity of different heparins is driven by a balance between different physical-chemical components, especially molecular size and fine-tuning composition. Although such minor but relevant chemical differences reinforce the concept that heparins from different animal sources should indeed be considered as distinct drugs, HOI could be approved for interchangeable use with the gold standard HPI and as a suitable start material for producing new LMWHs.

Keywords

anticoagulant - heparin - low-molecular-weight heparin - physical-chemical concepts - thromboembolism

Full Text

References

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Supplementary Material

Supplementary Material