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Prepublished online as a Blood First Edition Paper on March 27, 2003; DOI 10.1182/blood-2002-10-3150. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3150v1 102/2/535    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Cooper, A. V. Articles by Ariëns, R. A. S. Search for Related Content PubMed PubMed Citation Articles by Cooper, A. V. Articles by Ariëns, R. A. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2003, Vol. 102, No. 2, pp. 535-540 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Fibrinogen gamma-chain splice variant ' alters fibrin formation and structure Amy V. Cooper, Kristina F. Standeven, and Robert A. S. Ariëns From the Academic Unit of Molecular Vascular Medicine, University of Leeds, Martin Wing, Leeds General Infirmary, United Kingdom. Fibrinogen A/' results from alternative splicing of mRNA. This variant, which constitutes approximately 8% to 15% of plasma fibrinogen, contains FXIII and thrombin binding sites. Our objective was to investigate whether A/' differs in fibrin formation and structure from the more common variant A/A. Both variants were separated and purified by anion-exchange chromatography. Fibrin formation and clot structure of the variants and unfractionated fibrinogen were investigated by turbidity and scanning electron microscopy (SEM). Thrombin cleavage of fibrinopeptides was analyzed by high-performance liquid chromatography (HPLC). Turbidity analysis showed significantly altered polymerization rates and overall fiber thickness in A/' clots compared with A/A and unfractionated fibrinogen. This finding was consistent with a range of thrombin concentrations. HPLC demonstrated reduced rates of fibrinopeptide B (FpB) release from A/' fibrinogen compared with A/A. Delayed FpB release was associated with delayed lateral aggregation of protofibrils and significant differences were found on SEM, with A/' clots consisting of smaller diameter fibers and increased numbers of branch points compared with both A/A and unfractionated fibrinogen. These results demonstrate that the A/' splice variant of fibrinogen directly alters fibrin formation and structure, which may help to explain the increased thrombotic risk associated with this variant. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M van Oijen, E Y L Cheung, C E M Geluk, A Hofman, P J Koudstaal, M M B Breteler, and M P de Maat Haplotypes of the fibrinogen gene and cerebral small vessel disease: the Rotterdam scan study J. Neurol. Neurosurg. Psychiatry, July 1, 2008; 79(7): 799 - 803. [Abstract] [Full Text] [PDF] J. C. Fredenburgh, A. R. Stafford, B. A. Leslie, and J. I. Weitz Bivalent Binding to {gamma}A/{gamma}'-Fibrin Engages Both Exosites of Thrombin and Protects It from Inhibition by the Antithrombin-Heparin Complex J. Biol. Chem., February 1, 2008; 283(5): 2470 - 2477. [Abstract] [Full Text] [PDF] C. V. Bamford, J. C. Fenno, H. F. Jenkinson, and D. 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