|
|
 Previous Article | Table of Contents | Next Article 
Factors IXa and Xa play distinct roles in tissue factor-dependent
initiation of coagulation
M Hoffman, DM Monroe, JA Oliver and HR Roberts
Department of Pathology, Durham Veterans Affairs Medical Center, Durham, NC
27705, USA.
Tissue factor is the major initiator of coagulation. Both factor IX and
factor X are activated by the complex of factor VIIa and tissue factor
(VIIa/TF). The goal of this study was to determine the specific roles of
factors IXa and Xa in initiating coagulation. We used a model system of in
vitro coagulation initiated by VIIa/TF and that included unactivated
platelets and plasma concentrations of factors II, V, VIII, IX, and X,
tissue factor pathway inhibitor, and antithrombin III. In some cases,
factor IX and/or factor X were activated by tissue factor- bearing
monocytes, but in some experiments, picomolar concentrations of
preactivated factor IX or factor X were used to initiate the reactions.
Timed samples were assayed for both platelet activation and thrombin
activity. Factor Xa was 10 times more potent than factor IXa in initiating
platelet activation, but factor IXa was much more effective in promoting
thrombin generation than was factor Xa. In the presence of VIIa/TF, factor
X was required for both platelet activation and thrombin generation, while
factor IX was only required for thrombin generation. We conclude that
VIIa/TF-activated factors IXa and Xa have distinct physiologic roles. The
main role of factor Xa that is initially activated by VIIa/TF is to
activate platelets by generating an initial, small amount of thrombin in
the vicinity of platelets. Factor IXa, on the other hand, enhances thrombin
generation by providing factor Xa on the platelet surface, leading to
prothrombinase formation. Only tiny amounts of factors IX and X need to be
activated by VIIa/TF to perform these distinct functions. Our experiments
show that initiation of coagulation is highly dependent on activation of
small amounts of factors IXa and Xa in proximity to platelet surfaces and
that these factors play distinct roles in subsequent events, leading to an
explosion of thrombin generation. Furthermore, the specific roles of
factors IXa and Xa generated by VIIa/TF are not necessarily reflected by
the kinetics of factor IXa and Xa generation.
Volume 86,
Issue 5,
pp. 1794-1801,
09/01/1995
Copyright © 1995 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:
|
|
|
|
 
Y. Buyue and J. P. Sheehan
Fucosylated chondroitin sulfate inhibits plasma thrombin generation via targeting of the factor IXa heparin-binding exosite
Blood,
October 1, 2009;
114(14):
3092 - 3100.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Romney and M. Glick
An Updated Concept of Coagulation With Clinical Implications
J Am Dent Assoc,
May 1, 2009;
140(5):
567 - 574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Buyue, H. C. Whinna, and J. P. Sheehan
The heparin-binding exosite of factor IXa is a critical regulator of plasma thrombin generation and venous thrombosis
Blood,
October 15, 2008;
112(8):
3234 - 3241.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. L. Howard, K. C.D. Becker, C. P. Rusconi, and R. C. Becker
Factor IXa Inhibitors as Novel Anticoagulants
Arterioscler Thromb Vasc Biol,
April 1, 2007;
27(4):
722 - 727.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zhou, A. S. Wolberg, and R. A. S. Roubey
Characterization of monocyte tissue factor activity induced by IgG antiphospholipid antibodies and inhibition by dilazep
Blood,
October 15, 2004;
104(8):
2353 - 2358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Lu, G. J. Broze Jr., and S. Krishnaswamy
Formation of Factors IXa and Xa by the Extrinsic Pathway: DIFFERENTIAL REGULATION BY TISSUE FACTOR PATHWAY INHIBITOR AND ANTITHROMBIN III
J. Biol. Chem.,
April 23, 2004;
279(17):
17241 - 17249.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Bates and J. I. Weitz
Emerging Anticoagulant Drugs
Arterioscler Thromb Vasc Biol,
September 1, 2003;
23(9):
1491 - 1500.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. V. Potapov, M. Pasic, M. Bauer, and R. Hetzer
Activated recombinant factor VII for control of diffuse bleeding after implantation of ventricular assist device
Ann. Thorac. Surg.,
December 1, 2002;
74(6):
2182 - 2183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. R. Deitcher, T. L. Carman, and K. Kottke-Marchant
Simultaneous Deep Venous Thrombosis and Acquired Factor VIII Inhibitor
Clinical and Applied Thrombosis/Hemostasis,
October 1, 2002;
8(4):
375 - 379.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D. M. Monroe, M. Hoffman, and H. R. Roberts
Platelets and Thrombin Generation
Arterioscler Thromb Vasc Biol,
September 1, 2002;
22(9):
1381 - 1389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Weitz and J. Hirsh
New Anticoagulant Drugs
Chest,
January 1, 2001;
119
(2009):
95S - 107S.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Z. Feuerstein, A. Patel, J. R. Toomey, P. Bugelski, A. J. Nichols, W. R. Church, R. Valocik, P. Koster, A. Baker, and M. N. Blackburn
Antithrombotic Efficacy of a Novel Murine Antihuman Factor IX Antibody in Rats
Arterioscler Thromb Vasc Biol,
October 1, 1999;
19(10):
2554 - 2562.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Oliver, D. M. Monroe, H. R. Roberts, and M. Hoffman
Thrombin Activates Factor XI on Activated Platelets in the Absence of Factor XII
Arterioscler Thromb Vasc Biol,
January 1, 1999;
19(1):
170 - 177.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Cawthern, C. van `t Veer, J. B. Lock, M. E. DiLorenzo, R. F. Branda, and K. G. Mann
Blood Coagulation in Hemophilia A and Hemophilia C
Blood,
June 15, 1998;
91(12):
4581 - 4592.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Butenas, C. van `t Veer, and K. G. Mann
Evaluation of the Initiation Phase of Blood Coagulation Using Ultrasensitive Assays for Serine Proteases
J. Biol. Chem.,
August 22, 1997;
272(34):
21527 - 21533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Sekiya, M. Yoshida, T. Yamashita, and T. Morita
Magnesium(II) Is a Crucial Constituent of the Blood Coagulation Cascade
J. Biol. Chem.,
April 12, 1996;
271(15):
8541 - 8544.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
