Effect of endothelium on the anticoagulant activity of a covalent antithrombin-heparin complex.

Autor: Atkinson HM; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.; Department of Pediatrics, McMaster University, Hamilton, ON, Canada., Stevic I; Pathology and Laboratory Medicine, London Health Sciences Centre and Western University, London, ON, Canada., Berry LR; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.; Department of Pediatrics, McMaster University, Hamilton, ON, Canada., Chan AKC; Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada. akchan@mcmaster.ca.; Department of Pediatrics, McMaster University, Hamilton, ON, Canada. akchan@mcmaster.ca.; Thrombosis and Atherosclerosis Research Institute (TaARI), DBCVSRI, Hamilton General Hospital, 237 Barton St. E., Hamilton, ON, L8L 2X2, Canada. akchan@mcmaster.ca.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Sep 27; Vol. 14 (1), pp. 22335. Date of Electronic Publication: 2024 Sep 27.
DOI: 10.1038/s41598-024-72458-0
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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