Summary
A recent study (Fernandez et al., Thromb. Haemostas. 1987; 57: 286-93) demonstrated
that when rabbits were injected with the minimum weight of a variety of glycosaminoglycans
required to inhibit tissue factor-induced thrombus formation by —80%, exogenous thrombin
was inactivated —twice as fast in the post-treatment plasmas as the pre-treatment
plasmas. In this study, we investigated the relationship between inhibition of thrombus
formation and the extent of thrombin inhibition ex vivo. We also investigated the
relationship between inhibition of thrombus formation and inhibition of prothrombin
activation ex vivo. Four sulfated polysaccharides (SPS) which influence coagulation
in a variety of ways were used in this study. Unfractionated heparin and the fraction
of heparin with high affinity to antithrombin III potentiate the antiproteinase activity
of antithrombin III. Pentosan polysulfate potentiates the activity of heparin cofactor
II. At less than 10 pg/ml of plasma, all three SPS also inhibit intrinsic prothrombin
activation. The fourth agent, dermatan sulfate, potentiates the activity of heparin
cofactor II but fails to inhibit intrinsic prothrombin activation even at concentrations
which exceed 60 pg/ml of plasma. Inhibition of thrombus formation by each sulfated
polysaccharides was linearly related to the extent of thrombin inhibition achieved
ex vivo. These observations confirm the utility of catalysis of thrombin inhibition
as an index for assessing antithrombotic potential of glycosaminoglycans and other
sulfated polysaccharides in rabbits. With the exception of pentosan polysulfate, there
was no clear relationship between inhibition of thrombus formation and inhibition
of prothrombin activation ex vivo.
Keywords
Antithrombotic effects - Thrombin inhibition - Sulfated poly-saccharides
