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This kinetic study elucidates that heparin accelerates the antithrombin III-thrombin reaction via the formation of a ternary complex, rather than acting directly on fibrinogen.
The inhibitory effect of heparin and antithrombin III (AT) on the interaction of fibrinogen and thrombin was investigated in preference to studies on heparinizing devices. The turbidity was measured kinetically as a measure of the concentration of fibrin polymer formed in the system. It was found that AT did not act on fibrinogen but, rather, on thrombin, and the main role of heparin is to accelerate the AT-thrombin reaction. On the other hand, dextran sulfate (DSc) did not accelerate the AT-thrombin reaction. When heparin and AT were incubated with thrombin, inhibition did not depend on the mixing order but on the incubation time. Thus, a ternary complex of heparin, AT, and thrombin was supposed to form for the inhibition. The reaction of heparin with fibrinogen and thrombin in the presence of AT was well-explained by assuming a Freundlich-type adsorption of heparin analogous with the reaction of heparin with fibrinogen.
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Nakanishi et al. (1987) studied this question.
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