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

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Abstract
Thrombogenicity of 3 highly purified proteases (thrombin [bovine], activated Factor X [Vipera russelli] and activated Factor IX [bovine]), 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 administration of heparin at 5, 10 and 20 units/kg in rabbits, the thrombogenicity of each of these proteases decreased progressively. 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. The hypotheses supported from the originally developed in vitro experiments were activation of the blood coagulation system, which proceeds through a cascade mechanism and incorporates biochemical amplification; inhibition of activated Factor IX by antithrombin III [rabbit] in the presence of heparin is an important reaction in prevention of thrombosis; less heparin is required to inhibit thrombosis prior to thrombin generation than afterward; and an increase in reactivity of antithrombin III reflects a decreased tendency to thrombosis while a decrease in this reactivity reflects an increased tendency to thrombosis.