title: In vitro and in vivo correlation of clotting protease activity: effect of heparin.
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.
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005164:Factor IX / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005170:Factor X / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology*; D011817:Rabbits; D012910:Snake Venoms / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood
chemical_list: D000991:Antithrombins; D012910:Snake Venoms; D005164:Factor IX; D005170:Factor X; D006493:Heparin; D013917:Thrombin
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