|
|
 Previous Article | Table of Contents | Next Article 
The relative importance of thrombin inhibition and factor Xa inhibition to
the antithrombotic effects of heparin
MR Buchanan, B Boneu, F Ofosu and J Hirsh
The relative importance of antithrombin and anti-factor Xa activities of
heparin fractions required to achieve optimal antithrombotic effects is
unknown. To study this, we measured the effects of standard heparin, an
octasaccharide heparin fraction (anti-factor Xa activity only), and
dermatan sulfate (antithrombin activity only) on the prevention of
thrombosis and related this to their anticoagulant effects in vivo in
rabbits. Thrombosis was measured as the incorporation of 125I- fibrinogen
into tissue thromboplastin-induced thrombi using a Wessler- type model. Ex
vivo changes in thrombin clotting time (TCT) were used as an index of
antithrombin activity, and a chromogenic anti-factor Xa assay was used to
measure anti-factor Xa activity. In addition, the ability of the three
sulfated polysaccharides to simultaneously inhibit the generation of
thrombin activity and to enhance the inactivation of the factor Xa added to
initiate thrombin generation in plasma was determined. Standard heparin, in
a dose of 10 anti-factor Xa U/kg, inhibited thrombus formation by 90%,
prolonged the TCT by two seconds, and resulted in an anti-factor Xa level
of 0.32 U/mL. The octasaccharide heparin fraction, in a dose of 10
anti-factor Xa U/kg, inhibited thrombus formation by 41%, had no effect on
the TCT, and resulted in an anti-factor Xa level of 0.28 U/mL. Higher doses
of the octasaccharide resulted in a further increase in the anti-factor Xa
levels but had no further effect on thrombus formation. Dermatan sulfate,
in a dose of 500 micrograms/kg, inhibited thrombus formation by 95%, but
had no affect on the TCT. These results indicate that the antithrombotic
effect achieved by inhibiting factor Xa is limited and that better
antithrombotic effects are achieved by heparin or heparin- like substances
capable of influencing the inactivation and/or the generation of thrombin.
Volume 65,
Issue 1,
pp. 198-201,
01/01/1985
Copyright © 1985 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. P. Vicente, L. He, M. S. G. Pavao, and D. M. Tollefsen
Antithrombotic activity of dermatan sulfate in heparin cofactor II-deficient mice
Blood,
December 15, 2004;
104(13):
3965 - 3970.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lorrain, L. Millet, I. Lechaire, S. Lochot, P. Ferrari, C. Visconte, M. Sainte-Marie, C. Lunven, C. N. Berry, P. Schaeffer, et al.
Antithrombotic Properties of SSR182289A, a New, Orally Active Thrombin Inhibitor
J. Pharmacol. Exp. Ther.,
February 1, 2003;
304(2):
567 - 574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.M. Herbert, J.P. Herault, A. Bernat, R.G.M. van Amsterdam, J.C. Lormeau, M. Petitou, C. van Boeckel, P. Hoffmann, and D.G. Meuleman
Biochemical and Pharmacological Properties of SANORG 34006, a Potent and Long-Acting Synthetic Pentasaccharide
Blood,
June 1, 1998;
91(11):
4197 - 4205.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Hérault, A. Bernat, A. M. Pflieger, J. C. Lormeau, and J. M. Herbert
Comparative Effects of Two Direct and Indirect Factor Xa Inhibitors on Free and Clot-Bound Prothrombinase
J. Pharmacol. Exp. Ther.,
October 1, 1997;
283(1):
16 - 22.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. J. Kandrotas
State-of-the-Art Review: Pharmacology and Pharmacokinetics of Antithrombotic Agents
Clinical and Applied Thrombosis/Hemostasis,
July 1, 1997;
3(3):
157 - 164.
[PDF]
|
|
|
|
|
|
|
J.M. Herbert, J.P. Herault, A. Bernat, R.G.M. van Amsterdam, G.M.T. Vogel, J.C. Lormeau, M. Petitou, and D.G. Meuleman
Biochemical and Pharmacological Properties of SANORG 32701: Comparison With the `Synthetic Pentasaccharide' (SR 90107/ORG 31540) and Standard Heparin
Circ. Res.,
September 1, 1996;
79(3):
590 - 600.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
G. Agnelli, A. Iorio, C. Renga, E. Boschetti, G. G. Nenci, F. A. Ofosu, and J. Hirsh
Prolonged Antithrombin Activity of Low-Molecular-Weight Heparins : Clinical Implications for the Treatment of Thromboembolic Diseases
Circulation,
November 15, 1995;
92(10):
2819 - 2824.
[Abstract]
[Full Text]
|
|
|
|
|
