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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1977 Jul;74(7):3028–3032. doi: 10.1073/pnas.74.7.3028

In vitro and in vivo correlation of clotting protease activity: Effect of heparin

Sanford N Gitel 1, Ronald C Stephenson 1, Stanford Wessler 1
PMCID: PMC431395  PMID: 268650

Abstract

The thrombogenicity of three highly purified proteases (thrombin, activated Factor X, and activated Factor IX) was determined quantitatively in an animal model. The minimal amounts required to produce a standard score 4 thrombus were 1.1 nmol for thrombin, 0.12 nmol for activated Factor X, and 0.018 nmol for activated Factor IX. After the administration of heparin at 5, 10, and 20 units/kg in rabbits, the thrombogenicity of each of these proteases decreased progressively. The heparin-induced inhibition of thrombosis decreased in the order, activated Factor IX > activated Factor X > thrombin at each heparin concentration. These differences were statistically significant.

These in vivo data provide support for the following hypotheses originally developed from in vitro experiments: (i) activation of the blood coagulation system, which proceeds through a cascade mechanism, incorporates biochemical amplification; (ii) the inhibition of activated Factor IX by antithrombin III in the presence of heparin is an important reaction in the prevention of thrombosis; (iii) less heparin is required to inhibit thrombosis prior to thrombin generation than afterward; (iv) an increase in the reactivity of antithrombin III reflects a decreased tendency to thrombosis while a decrease in this reactivity reflects an increased tendency to thrombosis.

Keywords: coagulation, antithrombin III, animal model

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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