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Biol Pharm Bull. 2000 Apr;23(4):502-5.

Most clot-bound thrombin activity is inhibited by plasma antithrombin during clot aging, but a very small fraction survives.

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  • 1Pharmaceuticals & Biotechnology Laboratory, Japan Energy Corporation, Toda, Saitama.


Inhibitory effects of thrombin inhibitors against clot-bound thrombin have been evaluated using clots prepared from human plasma as the source of clot-immobilized active enzyme, and the clot-bound thrombin has been reported to be protected from its inhibition by antithrombin. However, we found that the clot-bound thrombin was not intrinsically protected from inhibition by antithrombin, i.e., a large fraction of initially active clot-bound thrombin was inhibited by antithrombin present in human plasma time dependently, and only very small fractions (0.04--0.08%) of the thrombin retained their enzymatic activity after clot-aging. These results suggest that the extent of clot-aging determines the sensitivity of clot-bound thrombin to antithrombin, and that inhibitory effects of drugs against clot-bound thrombin in vitro must be interpreted with caution to estimate their effects in vivo.

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