SEARCH:   Advanced

This Article Full Text Full Text (PDF) 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 Madoiwa, S. Articles by Sakata, Y. Search for Related Content PubMed PubMed Citation Articles by Madoiwa, S. Articles by Sakata, Y. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2001, Vol. 97, No. 12, pp. 3783-3789 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Autoantibody against prothrombin aberrantly alters the proenzyme to facilitate formation of a complex with its physiological inhibitor antithrombin III without thrombin conversion Seiji Madoiwa, Yuichi Nakamura, Jun Mimuro, Shinpei Furusawa, Takatoshi Koyama, Teruko Sugo, Michio Matsuda, and Yoichi Sakata From the Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, Minamikawachi-machi; the Third Department of Internal Medicine, Dokkyo University School of Medicine, Mibu-machi, Tochigi; and the First Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. Acquired coagulation factor inhibitors include pathologic immunoglobulins that specifically bind to coagulation factors and either neutralize their procoagulant activity, accelerate their clearance from the circulation, or have proteolytic activity to degrade them into inactive polypeptides. Here, an autoantibody against prothrombin is described in a patient with serious hemorrhagic diatheses. The autoantibody exerts its influence by a previously unknown mechanism in which it inhibits coagulation through aberrant activation of the proenzyme in a catalytic manner. The antibody-bound prothrombin formed a stable stoichiometric complex with antithrombin III, consisting of intact prothrombin and an antithrombin III molecule cleaved at the 393Arg-394Ser bond. The antibody dissociated from prothrombin after the complex formation with antithrombin III. Although the bound antibody elicited protease activity from prothrombin, the complex was not able to convert fibrinogen to fibrin or to activate protein C. Thus, this is the first description of an autoantibody that induces protease-like activity from a human proenzyme, permitting subsequent neutralization by its physiological inhibitor. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Toso, H. Zhu, and R. M. Camire The Conformational Switch from the Factor X Zymogen to Protease State Mediates Exosite Expression and Prothrombinase Assembly J. Biol. Chem., July 4, 2008; 283(27): 18627 - 18635. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020