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Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: implications for heparin efficacy.
Open accessAbstract
Fibrin II monomer has a dramatic inhibitory effect on the rate of heparin-catalyzed inactivation of human alpha-thrombin by antithrombin III. At 6 microM fibrin II monomer, equivalent to the concentration of fibrinogen in plasma, the second-order rate constant was reduced by a factor of 308--from 2.05 x 10(8) M-1.s-1 to 6.65 x 10(5) M-1.s-1. Fibrin II monomer minimally affected the uncatalyzed rate of thrombin inactivation showing a reduction in the second-order rate constant by a factor of only 1.6. Fibrinogen and the product of plasmin degradation of fibrinogen, fragment E, at 6 microM concentrations also decreased the second-order rate constant for heparin-catalyzed thrombin inactivation, but by factors of only 2.7 and 1.9, respectively. On the basis of these observations it is proposed that protection of thrombin from inactivation by heparin-antithrombin III by fibrin II monomer can explain the limited efficacy of heparin in preventing coronary reocclusion in patients treated with tissue plasminogen activator and other fibrinolytic agents.
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Cited by
Weitz, J. I., Hudoba, M., Massel, D., Maraganore, J., & Hirsh, J. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114723 · Cited by 1,123
Oates, J. A., Wood, A. J. J., & Hirsh, J. (1991) · New England Journal of Medicine · doi:10.1056/nejm199105303242206 · Cited by 830
Thrombin generation and fibrin clot structure
Wolberg, A. S. (2007) · Blood Reviews · doi:10.1016/j.blre.2006.11.001 · Cited by 747
A player of many parts: The spotlight falls on thrombin's structure
Stubbs, M. T., & Bode, W. (1993) · Thrombosis Research · doi:10.1016/0049-3848(93)90002-6 · Cited by 441
Griffin, L., Tidmarsh, G., Bock, L., Toole, J., & Leung, L. (1993) · Blood · doi:10.1182/blood.v81.12.3271.3271 · Cited by 285
Metadata
- Authors
- Hogg, P. J., & Jackson, C. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1989-05
- Volume
- 86
- Issue
- 10
- Pages
- 3619-3623
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2085873519
- Cited by
- 347
- References
- 0
- FWCI
- 11.42
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hogg, P. J., & Jackson, C. M. (1989). Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: implications for heparin efficacy. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.86.10.3619
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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