|
|
Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-08-2527.
Previous Article | Table of Contents | Next Article 
Blood, 15 April 2003, Vol. 101, No. 8, pp. 3008-3013
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Elevated prothrombin results in clots with an altered fiber
structure: a possible mechanism of the increased thrombotic
risk
Alisa S. Wolberg,
Dougald
M. Monroe,
Harold R. Roberts, and
Maureane Hoffman
From the Department of Pathology and Laboratory
Medicine, and Department of Medicine and Center for Thrombosis and
Hemostasis, University of North Carolina, Chapel Hill; Department of
Pathology, Duke University Medical Center, Durham, NC; and Durham
Veterans Affairs Medical Center, Durham, NC.
Individuals with elevated prothrombin levels are at increased risk
of venous thrombosis. To understand the mechanism behind this
observation, we studied the effect of prothrombin concentration on
thrombin generation and fibrin clot structure. The pattern of thrombin
generation was directly related to the prothrombin level at all
concentrations tested. From 0% to 300% of normal plasma levels of
prothrombin, increasing the prothrombin concentration increased the
initial rate, peak, and total amount of thrombin generated.
Importantly, fibrin clot structure was also affected by the prothrombin
concentration. Fibrin clots made from prothrombin concentrations less
than 10% of plasma levels were weak and poorly formed. Fibrin clots
made at 10% to 100% of plasma levels of prothrombin had similar fiber
structures (mass-to-length ratio; µ). However, the fiber
mass-to-length ratio decreased with increasing prothrombin levels more
than 100% of plasma levels, in a dose-dependent manner. These results
suggest that increased levels of prothrombin alter thrombin generation
and clot structure. Specifically, elevated prothrombin levels produce
clots with reduced fibrin mass-to-length ratios compared with normal
clots. We hypothesize that this alteration in fibrin clot structure is
an important determinant of the risk of thrombosis.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
R. A. Campbell, K. A. Overmyer, C. R. Bagnell, and A. S. Wolberg
Cellular Procoagulant Activity Dictates Clot Structure and Stability as a Function of Distance From the Cell Surface
Arterioscler Thromb Vasc Biol,
December 1, 2008;
28(12):
2247 - 2254.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. A. Smith and J. H. Morrissey
Polyphosphate enhances fibrin clot structure
Blood,
October 1, 2008;
112(7):
2810 - 2816.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. A. Allen, E. Persson, R. A. Campbell, M. Ezban, U. Hedner, and A. S. Wolberg
A Variant of Recombinant Factor VIIa With Enhanced Procoagulant and Antifibrinolytic Activities in an In Vitro Model of Hemophilia
Arterioscler Thromb Vasc Biol,
March 1, 2007;
27(3):
683 - 689.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Undas, J. Brozek, M. Jankowski, Z. Siudak, A. Szczeklik, and H. Jakubowski
Plasma Homocysteine Affects Fibrin Clot Permeability and Resistance to Lysis in Human Subjects
Arterioscler Thromb Vasc Biol,
June 1, 2006;
26(6):
1397 - 1404.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. M. Monroe and M. Hoffman
What Does It Take to Make the Perfect Clot?
Arterioscler Thromb Vasc Biol,
January 1, 2006;
26(1):
41 - 48.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. R. Roberts, D. M. Monroe, and G. C. White
The use of recombinant factor VIIa in the treatment of bleeding disorders
Blood,
December 15, 2004;
104(13):
3858 - 3864.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. M. Scott, R. A.S. Ariens, and P. J. Grant
Genetic and Environmental Determinants of Fibrin Structure and Function: Relevance to Clinical Disease
Arterioscler Thromb Vasc Biol,
September 1, 2004;
24(9):
1558 - 1566.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Colucci, B. M. Binetti, A. Tripodi, V. Chantarangkul, and N. Semeraro
Hyperprothrombinemia associated with prothrombin G20210A mutation inhibits plasma fibrinolysis through a TAFI-mediated mechanism
Blood,
March 15, 2004;
103(6):
2157 - 2161.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. V. Cooper, K. F. Standeven, and R. A. S. Ariens
Fibrinogen gamma-chain splice variant {gamma}' alters fibrin formation and structure
Blood,
July 15, 2003;
102(2):
535 - 540.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|