Skip to main content
Journal cover image

Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion.

Publication ,  Journal Article
Telen, MJ; Batchvarova, M; Shan, S; Bovee-Geurts, PH; Zennadi, R; Leitgeb, A; Brock, R; Lindgren, M
Published in: Br J Haematol
December 2016

Sevuparin is a novel drug candidate in phase II development as a treatment for vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD). As a heparin-derived polysaccharide, sevuparin has been designed to retain anti-adhesive properties, while the antithrombin-binding domains have been eliminated, substantially diminishing its anticoagulant activity. Here, we demonstrate that sevuparin inhibits the adhesion of human sickle red blood cells (SS-RBCs) to stimulated cultured endothelial cells in vitro. Importantly, sevuparin prevents vaso-occlusion and normalizes blood flow in an in vivo mouse model of SCD vaso-occlusion. Analyses by surface plasmon resonance (SPR) and fluorescence correlation spectroscopy (FCS) demonstrate that sevuparin binds to P- and L-selectins, thrombospondin, fibronectin and von Willebrand factor, all of which are thought to contribute to vaso-occlusion in SCD. Despite low anticoagulation activity, sevuparin has anti-adhesive efficacy similar to the low molecular weight heparin tinzaparin both in vitro and in vivo. These results suggest that the anti-adhesive properties rather than the anticoagulant effects of heparinoids are critical for the treatment of vaso-occlusion in SCD. Therefore, sevuparin is now being evaluated in SCD patients hospitalized for treatment of VOC.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Br J Haematol

DOI

EISSN

1365-2141

Publication Date

December 2016

Volume

175

Issue

5

Start / End Page

935 / 948

Location

England

Related Subject Headings

  • Tinzaparin
  • Protein Binding
  • Mice
  • Immunology
  • Humans
  • Heparin, Low-Molecular-Weight
  • Heparin
  • Erythrocytes
  • Endothelial Cells
  • Cells, Cultured
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Telen, M. J., Batchvarova, M., Shan, S., Bovee-Geurts, P. H., Zennadi, R., Leitgeb, A., … Lindgren, M. (2016). Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion. Br J Haematol, 175(5), 935–948. https://doi.org/10.1111/bjh.14303
Telen, Marilyn J., Milena Batchvarova, Siqing Shan, Petra H. Bovee-Geurts, Rahima Zennadi, Anna Leitgeb, Roland Brock, and Maria Lindgren. “Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion.Br J Haematol 175, no. 5 (December 2016): 935–48. https://doi.org/10.1111/bjh.14303.
Telen MJ, Batchvarova M, Shan S, Bovee-Geurts PH, Zennadi R, Leitgeb A, et al. Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion. Br J Haematol. 2016 Dec;175(5):935–48.
Telen, Marilyn J., et al. “Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion.Br J Haematol, vol. 175, no. 5, Dec. 2016, pp. 935–48. Pubmed, doi:10.1111/bjh.14303.
Telen MJ, Batchvarova M, Shan S, Bovee-Geurts PH, Zennadi R, Leitgeb A, Brock R, Lindgren M. Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion. Br J Haematol. 2016 Dec;175(5):935–948.
Journal cover image

Published In

Br J Haematol

DOI

EISSN

1365-2141

Publication Date

December 2016

Volume

175

Issue

5

Start / End Page

935 / 948

Location

England

Related Subject Headings

  • Tinzaparin
  • Protein Binding
  • Mice
  • Immunology
  • Humans
  • Heparin, Low-Molecular-Weight
  • Heparin
  • Erythrocytes
  • Endothelial Cells
  • Cells, Cultured