Thromb Haemost 1988; 60(02): 188-192
DOI: 10.1055/s-0038-1647027
Original Article
Schattauer GmbH Stuttgart

Further Studies on the Mechanisms for the Antithrombotic Effects of Sulfated Polysaccharides in Rabbits

F A Ofosu
a   The McMaster University, Gennevilliers, France
,
F Fernandez
a   The McMaster University, Gennevilliers, France
,
N Anvari
a   The McMaster University, Gennevilliers, France
,
C Caranobe
b   Canadian Red Cross Society, BTS, Hamilton, Ont. Canada, the Laboratoire d’Hemostase, Gennevilliers, France
,
F Dol
b   Canadian Red Cross Society, BTS, Hamilton, Ont. Canada, the Laboratoire d’Hemostase, Gennevilliers, France
,
Y Cadroy
b   Canadian Red Cross Society, BTS, Hamilton, Ont. Canada, the Laboratoire d’Hemostase, Gennevilliers, France
,
M Petitou
c   Centre de Transfusion Sanguine, Toulouse, France, the Institut Choay, Paris, France
,
J Mardiguian
d   The Laboratoires Pharmuka, Gennevilliers, France
,
P Sié
b   Canadian Red Cross Society, BTS, Hamilton, Ont. Canada, the Laboratoire d’Hemostase, Gennevilliers, France
,
B Boneu
b   Canadian Red Cross Society, BTS, Hamilton, Ont. Canada, the Laboratoire d’Hemostase, Gennevilliers, France
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 26. April 1988

Accepted after revision 22. Juni 1988

Publikationsdatum:
28. Juni 2018 (online)

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.

 
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