Effect of endothelium on the anticoagulant activity of a covalent antithrombin-heparin complex.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 Sep 2024
27 Sep 2024
Historique:
received:
29
11
2023
accepted:
06
09
2024
medline:
28
9
2024
pubmed:
28
9
2024
entrez:
28
9
2024
Statut:
epublish
Résumé
We developed a covalent antithrombin-heparin complex (ATH) with superior In vivo anticoagulant efficacy compared to non-covalent antithrombin (AT) + unfractionated heparin (H). Previous in vitro studies of ATH, investigating the mechanisms behind its efficacy, were done in the absence of endothelium. Since the endothelial surface modulates hemostasis, we investigated its impact on the in vitro anticoagulant properties of ATH and AT+H. Discontinuous second order rate constant enzyme inhibition assays, fibrin formation, and plasma clot generation were performed in the presence of ATH or AT+H, with and without endothelium present. ATH had an increased rate of direct inhibition of IIa and Xa, and increased inhibition of IIa-induced fibrin formation, compared to AT+H. When compared at equal anti-Xa levels, ATH was less effective than AT+H at catalyzing inhibition of plasma clot generation. These results were found in both the presence and absence of endothelium. Endothelium decreased the rate of IIa inhibition, and reduced clot time in IIa-induced fibrin formation and plasma clot generation assays, for both ATH and AT+H. Endothelium did not impact the activity of ATH differently to AT+H. This supports the growing body of evidence suggesting ATH may be a beneficial anticoagulant for potential clinical use.
Identifiants
pubmed: 39333740
doi: 10.1038/s41598-024-72458-0
pii: 10.1038/s41598-024-72458-0
doi:
Substances chimiques
Heparin
9005-49-6
Antithrombins
0
Anticoagulants
0
Fibrin
9001-31-4
Factor Xa
EC 3.4.21.6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
22335Informations de copyright
© 2024. The Author(s).
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