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Next Article 
The pathophysiology of the prethrombotic state in humans: insights gained
from studies using markers of hemostatic system activation
KA Bauer and RD Rosenberg
Numerous investigators have postulated that a hypercoagulable state exists
in humans for a period of time before the development of thrombotic
episodes. A clear biochemical definition of the prethrombotic state,
however, has proved elusive due in part to the lack of reliable techniques
for monitoring pertinent changes in blood coagulability. Based on recent
advances in our knowledge of the biochemistry of the coagulation system, a
series of highly sensitive and specific immunochemical tools has been
developed that can quantitate the activities of various steps of the
hemostatic mechanism in vivo at the subnanomolar level. We have established
assays for F1+2 and the protein C activation peptide, which measure the
cleavage of the prothrombin molecule by factor Xa and the scission of
protein C by the thrombin-thrombomodulin complex, respectively. Nossel and
coworkers had previously constructed similar assays for fibrinopeptide A
(FPA) and fragment B beta 1-42, which monitor the cleavage of fibrinogen by
thrombin and the proteolysis of fibrin I by plasmin, respectively.
Substantial elevations in the levels of these markers have been found in
patients with disseminated intravascular coagulation and many subjects with
acute deep venous thrombosis. The F1+2 and FPA assays have been used to
demonstrate that significant increments in factor Xa activity but not
thrombin activity regularly occur in the blood of nonanticoagulated
individuals with congenital deficiencies of antithrombin or protein C.
These two disorders are known to be correlated with the subsequent
development of thrombosis. Patients with protein C deficiency have also
been noted to have significantly reduced plasma levels of protein C
activation peptide. By using the immunoassays for FPA and B beta 1-42 in
studies of postoperative patients, it has been shown that an imbalance
between the procoagulant action of thrombin and the anticoagulant effect of
plasmin on fibrin I polymer may induce an acquired thrombotic diathesis.
Finally, we have recently demonstrated that prothrombin activation as
measured by the F1+2 assay is suppressed by oral anticoagulants in the
blood of patients with thrombotic diatheses. These investigations suggest
that these assay techniques can be used to improve our understanding of the
hypercoagulable state as well as to develop more effective treatment
strategies for the prevention of thromboembolic events.
Volume 70,
Issue 2,
pp. 343-350,
08/01/1987
Copyright © 1987 by The American Society of Hematology
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|
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|
|
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|
|
|
|
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|
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|
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|
|
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|
|
|
|
|
|
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|
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|
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|
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|
|
|
|
|
|
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|
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|
|
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|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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113(4):
742 - 747.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
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94(3):
331 - 339.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
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Clinical and Applied Thrombosis/Hemostasis,
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[Abstract]
[PDF]
|
|
|
|
|
|
|
B. W. Bottiger, J. Motsch, H. Bohrer, T. Boker, M. Aulmann, P. P. Nawroth, and E. Martin
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November 1, 1995;
92(9):
2572 - 2578.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
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October 1, 1995;
15(10):
1675 - 1679.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. Amiral
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Clinical and Applied Thrombosis/Hemostasis,
September 1, 1995;
1(4):
243 - 259.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. Fareed, R. L. Bick, D. A. Hoppensteadt, and E. W. Bermes
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Clinical and Applied Thrombosis/Hemostasis,
March 1, 1995;
1(2):
87 - 102.
[Abstract]
[PDF]
|
|
|
|
|
|
|
V. Salomaa, V. Stinson JD, J.D. Kark, A.R. Folsom, C.E. Davis, and K.K. Wu
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Circulation,
January 15, 1995;
91(2):
284 - 290.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
K. Yamamoto, U. Ikeda, and K. Shimada
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N. Engl. J. Med.,
April 8, 1993;
328(14):
1043 - 1044.
[Full Text]
|
|
|
|
|
|
|
A. Cogo, A. Lensing, P. Prandoni, G. Canova, R. De Toni, S. Cuppini, and A. Ruol
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Angiology,
December 1, 1992;
43(12):
975 - 979.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Fisher and R. Francis
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Arch Neurol,
October 1, 1990;
47(10):
1075 - 1079.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. M. Bern, J. J. Lokich, S. R. Wallach, A. Bothe Jr., P. N. Benotti, C. F. Arkin, F. A. Greco, M. Huberman, and C. Moore
Very Low Doses of Warfarin Can Prevent Thrombosis in Central Venous Catheters: A Randomized Prospective Trial
Ann Intern Med,
March 15, 1990;
112(6):
423 - 428.
[Abstract]
[PDF]
|
|
|
|
|
