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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-08-2527. This Article Full Text (PDF) All Versions of this Article: 2002-08-2527v1 101/8/3008    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wolberg, A. S Articles by Hoffman, M. Search for Related Content PubMed PubMed Citation Articles by Wolberg, A. S Articles by Hoffman, M. Social Bookmarking                   What's this? Submitted August 23, 2002 Accepted November 17, 2002 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* Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA Department of Medicine, University of North Carolina, Chapel Hill, NC, USA Center for Thrombosis and Hemostasis, Chapel Hill, NC, USA Department of Pathology, Duke University, Durham, NC, USA; Department of Laboratory Service, Durham VA Medical Center, Durham, NC, USA * Corresponding author; email: maureane{at}med.unc.edu. 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/length ratio; µ). However, the fiber mass/length ratio decreased with increasing prothrombin levels greater 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/length ratios compared to normal clots. 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