SEARCH:   Advanced

Blood, 15 April 2004, Vol. 103, No. 8, pp. 3045-3050. Prepublished online as a Blood First Edition Paper on January 8, 2004; DOI 10.1182/blood-2003-07-2569. This Article Full Text (PDF) All Versions of this Article: 2003-07-2569v1 103/8/3045    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 Hamano, A. Articles by Sakata, Y. Search for Related Content PubMed PubMed Citation Articles by Hamano, A. Articles by Sakata, Y. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted July 30, 2003 Accepted December 24, 2003 Thrombophilic Dysfibrinogen Tokyo V with the amino acid substitution of Ala-327 to Thr: Formation of fragile but fibrinolysis-resistant fibrin clots and its relevance to arterial thromboembolism Akiei Hamano, Jun Mimuro*, Motonori Aoshima, Takeyoshi Itoh, Noboru Kitamura, Susumu Nishinarita, Katsuhiro Takano, Akira Ishiwata, Yuji Kashiwakura, Kazuki Niwa, Tomoko Ono, Seiji Madoiwa, Teruko Sugo, Michio Matsuda, and Yoichi Sakata Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, Minami-kawachi, Tochigi-ken, Japan Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan Department of Internal Medicine, Akiru General Municipal Hospital, Tokyo, Japan * Corresponding author; email: mimuro-j{at}jichi.ac.jp. Thrombophilic dysfibrinogen Tokyo V was identified in a 43-year old male with recurrent thromboembolism. Based on analyses of the patient fibrinogen genes, the amino acid sequence of the aberrant fibrinogen peptide, and deglycosylation experiments, fibrinogen Tokyo V was shown to have an amino acid substitution of Ala-327 to Thr and possibly extra glycosylation at Asn-325 because the mutation confers the N-linked glycosylation consensus sequence Asn-X-Thr. The mutation resulted in impaired function and hypofibrinogenemia (hypo-dysfibrinogen). Polymerization of fibrin monomers derived from patient fibrinogen was severely impaired with a partial correction in the presence of calcium, resulting in very low clottability. Additionally, a large amount of soluble cross-linked fibrin was formed upon thrombin treatment in the presence of factor XIII and calcium. However, Tokyo V-derived fibrin was resistant to degradation by tPA-catalyzed plasmin digestion. The structure of Tokyo V fibrin appeared severely perturbed since there are large pores inside the tangled fibrin networks and fiber ends at the boundaries. Taken together, these data suggest that Tokyo V fibrin clots are fragile, so that fibrinolysis-resistant insoluble fibrin and soluble fibrin polymers may be released to the circulation, partly accounting for the recurrent embolic episodes in the patient. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Fibrinogen faux pas Victor J. Marder Blood 2004 103: 2867-2868. [Full Text] [PDF] This article has been cited by other articles: R. Park, H.-J. Doh, S.-S. A. An, J.-R. Choi, K.-H. Chung, and K.-S. Song A novel fibrinogen variant (fibrinogen Seoul II; A{alpha}Gln328Pro) characterized by impaired fibrin {alpha}-chain cross-linking Blood, September 15, 2006; 108(6): 1919 - 1924. [Abstract] [Full Text] [PDF] K. S. Song, N. J. Park, J. R. Choi, H. J. Doh, and K. H. Chung Fibrinogen Seoul (FGG Ala341Asp): A Novel Mutation Associated With Hypodysfibrinogenemia Clinical and Applied Thrombosis/Hemostasis, July 1, 2006; 12(3): 338 - 343. [Abstract] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020