|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 2064-2074
No Effect of Clot Age or Thrombolysis on Argatroban's Inhibition of
Thrombin
Roy R. Hantgan,
W. Gray Jerome, and
Marcie J. Hursting
From the Departments of Biochemistry and Pathology, Wake Forest
University School of Medicine, Winston-Salem, NC; and Texas
Biotechnology Corp, Houston, TX.
The purpose of this study was to establish the effects of clot age
and thrombolysis, with either streptokinase or tissue-type plasminogen
activator (tPA), on argatroban's ability to inhibit thrombin. The antithrombotic activity of argatroban has been quantified in fibrin clot permeation and fibrin clot perfusion systems as a
function of clot age and composition. Analysis of the argatroban dose-response data with a competitive inhibition model has yielded IC50 values in the low micromolar range. Results obtained
in a plasma clot permeation system have also shown that argatroban is a
potent inhibitor of clot-bound thrombin, independent of either clot age
or the presence of hemostatically active platelets. Treatment of aged
plasma clots with either streptokinase or alteplase, at therapeutic
levels, increased the available thrombin activity, yet argatroban still
inhibited this clot-associated thrombin with IC50 values in
the low micromolar range. Scanning electron microscopy/morphometric analyses demonstrated that permeation with argatroban had no
significant effects on clot structure. We conclude that argatroban is
an effective inhibitor of thrombin bound to aged fibrin clots, in
purified systems and in plasma clots, as well as in clots that have
been treated with the thrombolytic agents streptokinase and alteplase.
© 1998 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:
|
|
|
|
 
S.-C. Wu, F. J. Castellino, and S.-L. Wong
A Fast-acting, Modular-structured Staphylokinase Fusion with Kringle-1 from Human Plasminogen as the Fibrin-targeting Domain Offers Improved Clot Lysis Efficacy
J. Biol. Chem.,
May 9, 2003;
278(20):
18199 - 18206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Zhang, I. Nagata, H. Kikuchi, J-H. Xue, N. Sakai, H. Sakai, and H. Yanamoto
Broad-Spectrum and Selective Serine Protease Inhibitors Prevent Expression of Platelet-Derived Growth Factor-BB and Cerebral Vasospasm After Subarachnoid Hemorrhage : Vasospasm Caused by Cisternal Injection of Recombinant Platelet-Derived Growth Factor-BB
Stroke,
July 1, 2001;
32(7):
1665 - 1672.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. E. Lewis, D. E. Wallis, S. D. Berkowitz, W. H. Matthai, J. Fareed, J. M. Walenga, J. Bartholomew, R. Sham, R. G. Lerner, Z. R. Zeigler, et al.
Argatroban Anticoagulant Therapy in Patients With Heparin-Induced Thrombocytopenia
Circulation,
April 10, 2001;
103(14):
1838 - 1843.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Nakatani, S. Takeshita, H. Tsujimoto, Y. Kawamura, and I. Sekine
Inhibitory effect of serine protease inhibitors on neutrophil-mediated endothelial cell injury
J. Leukoc. Biol.,
February 1, 2001;
69(2):
241 - 247.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. S. Regier, D. G. Greene, S. Sergeant, A. J. Jesaitis, and L. C. McPhail
Phosphorylation of p22phox Is Mediated by Phospholipase D-dependent and -independent Mechanisms. CORRELATION OF NADPH OXIDASE ACTIVITY AND p22phox PHOSPHORYLATION
J. Biol. Chem.,
September 8, 2000;
275(37):
28406 - 28412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Palicz, T. R. Foubert, A. J. Jesaitis, L. Marodi, and L. C. McPhail
Phosphatidic Acid and Diacylglycerol Directly Activate NADPH Oxidase by Interacting with Enzyme Components
J. Biol. Chem.,
January 26, 2001;
276(5):
3090 - 3097.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
