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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2157-2161. Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-06-2169. This Article Full Text (PDF) All Versions of this Article: 2003-06-2169v1 103/6/2157    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 Colucci, M. Articles by Semeraro, N. Search for Related Content PubMed PubMed Citation Articles by Colucci, M. Articles by Semeraro, N. Social Bookmarking                   What's this? Submitted July 1, 2003 Accepted November 12, 2003 Hyperprothrombinemia associated with prothrombin G20210A mutation inhibits plasma fibrinolysis through a TAFI-mediated mechanism Mario Colucci*, Bianca M Binetti, Armando Tripodi, Veena Chantarangkul, and Nicola Semeraro Department of Biomedical Sciences, Section of General Pathology, University of Bari, Bari, Italy A Bianchi Bonomi, Hemophilia & Thrombosis Center, Department of Internal Medicine, University & IRCCS Maggiore Hospital, Milan, Italy * Corresponding author; email: mario.colucci{at}dimo.uniba.it. The prothrombin gene mutation G20210A is a common risk factor for thrombosis and is associated with increased prothrombin levels. However, the mechanism whereby hyperprothrombinemia predispose to thrombosis remains unclear. Since thrombin is the physiologic activator of TAFI (thrombin activatable fibrinolysis inhibitor), the precursor of an antifibrinolytic carboxypeptidase (TAFIa), we evaluated the influence of hyperprothrombinemia on fibrinolysis. Thirty-two heterozygous carriers of the G20210A mutation and 30 non carriers were studied. Plasma fibrinolytic factors and TAFI levels were similar in the two groups. Mean lysis time of tissue factor-induced plasma clots exposed to 25 ng/ml exogenous t-PA was significantly longer in 20210A carriers than in controls. This difference disappeared upon addition of a specific inhibitor of TAFIa. Determination of thrombin and TAFIa activity, generated during clot lysis, revealed that G20210A mutation was associated with a significant enhancement of late thrombin formation and an increase in TAFI activation. Plasma prothrombin level was highly significantly correlated with both clot lysis time and TAFI activation. The addition of purified prothrombin, but not of factors X or VIIa, to normal plasma caused a concentration-dependent, TAFI-mediated inhibition of fibrinolysis. These findings provide a new mechanism that might contribute to the thrombotic risk in prothrombin 20210A carriers. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Semeraro, C. T. Ammollo, N. Semeraro, and M. Colucci Tissue factor-expressing monocytes inhibit fibrinolysis through a TAFI-mediated mechanism, and make clots resistant to heparins Haematologica, June 1, 2009; 94(6): 819 - 826. [Abstract] [Full Text] [PDF] T. Brighton, J. Janssen, and S. P. Butler Aging of Acute Deep Vein Thrombosis Measured by Radiolabeled 99mTc-rt-PA J. Nucl. Med., June 1, 2007; 48(6): 873 - 878. [Abstract] [Full Text] [PDF] T. Lisman, P. G. de Groot, J. C.M. Meijers, and F. R. Rosendaal Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis Blood, February 1, 2005; 105(3): 1102 - 1105. [Abstract] [Full Text] [PDF] F. R. Rosendaal Venous Thrombosis: The Role of Genes, Environment, and Behavior Hematology, January 1, 2005; 2005(1): 1 - 12. [Abstract] [Full Text] [PDF]

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