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DOI: 10.1055/a-2516-7384
Heparin and Direct Oral Anticoagulants have Different Effects on the Phases of Activation and Spatial Spread of Blood Coagulation
Funding This work was supported by a grant from the Endowment foundation “Science for Children.”
Abstract
Background Various reactions are involved in the phases of activation and further propagation of coagulation in space. The effects of different anticoagulants on these phases are unknown. Our aim was to study how different anticoagulants affect the activation and propagation phases of coagulation.
Materials and Methods Coagulation in the presence of low-molecular-weight heparin (nadroparin), and direct oral thrombin or factor Xa inhibitors (dabigatran and rivaroxaban, respectively) was studied in vitro and ex vivo via a global blood coagulation assay (Thrombodynamics-4D), which allows simultaneous analysis of thrombin activity in space and the clot growth rate. The ex vivo measurements were carried out in dynamics (8–9 days). The presence of asymptomatic thrombosis after 7 to 8 days of treatment was determined for each group of patients via ultrasound of the lower extremities.
Results All the tested anticoagulants inhibited thrombin generation but resulted in different patterns of thrombin spatial distribution and clot growth. The reversible inhibitors—dabigatran and rivaroxaban—inhibited the initiation phase of coagulation, while further clot growth was altered moderately. Irreversible nadroparin weakly affected the initiation phase of thrombin generation, but unlike dabigatran and rivaroxaban, it could completely suppress spatial thrombin propagation. Asymptomatic thrombosis was observed in 0%, 11%, and 29% of the patients in the nadroparin, dabigatran, and rivaroxaban groups, respectively.
Conclusion Antithrombin-dependent and independent inhibitors act differently on different phases of coagulation. High concentrations of dabigatran or rivaroxaban are insufficient to completely prevent fibrin clot growth, but even small amounts of heparin completely suppress this growth, due to factor IXa inhibition.
Keywords
anticoagulants - blood coagulation - spatial clot growth rate - spatial thrombin distribution - Thrombodynamics-4DEthical Approval Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethical Committee of the Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences (Permit Number: 1/1-12 from December 1, 2014).
Data Availability Statement
All the data generated or analyzed during this study are included in the published article.
Authors' Contribution
F.I.A., N.M.D., A.N.B., and E.I.S. designed and supervised the research. N.M.D., R.A.O., T.A.V., A.N.B., and A.D.K. performed the experiments and collected data. D-C.B.A. and A.I.B. were responsible for patient recruitment and performed the operations. E.I.S. and N.M.D. wrote and edited the manuscript. All the authors reviewed and approved the final version of the manuscript.
Publikationsverlauf
Eingereicht: 12. November 2024
Angenommen: 12. Januar 2025
Artikel online veröffentlicht:
17. Februar 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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