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Blood, 15 March 2004, Vol. 103, No. 6, pp. 1977-1978. This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mosesson, M. W. Search for Related Content PubMed Articles by Mosesson, M. W. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Fibrinogen contributions to arterial thrombus formation: vessel size counts The C-terminal regions of fibrinogen chains contribute to platelet adhesion and aggregation, fibrin assembly and cross-linking, and platelet-mediated clot retraction. Several other fibrin functions are localized to other regions of the molecule, including one involving sequestration of thrombin ("antithrombin I").1 Until the article by Jirouková and colleagues (page 1995) in this issue of Blood, it was unclear how such functionalities, which can serve to either promote or limit thrombosis, contributed to arterial thrombus formation. Their study has made some important inroads toward solving this puzzle by meticulously comparing thrombus formation in the carotid arteries of afibrinogenemic mice (fbg–/–) with that occurring in mice whose fibrinogen molecules lacked the chain platelet-binding motif (5), or in wild-type mice that had been treated with 7E9, a blocking antibody to the fibrinogen chain C-terminus. Large thrombi formed in fbg–/– mice, no doubt reflecting thrombin-mediated platelet thrombus formation. Consistent with previous studies, such platelet thrombi abruptly embolized downstream. In contrast, 5 mice or wild-type mice treated with 7E9 developed only small, nonocclusive mural thrombi that had a limited tendency to embolize. Such thrombi could not recruit platelets into the thrombus, but they retained their ability to polymerize and to bind and sequester thrombin, suggesting that this sequence of events provided the basis for the reduced effect. In contrast, previous investigations of smaller-caliber arterial vessels (mesenteric arterioles) had demonstrated a greater tendency for thrombi from 5 mice to embolize as well as to form an occlusive thrombus.2 Taken together, the findings indicate that differences in blood vessel size contribute to the complexity of fibrinogen's prothrombotic and antithrombotic effects. Such differences need to be taken into account when the efficacy of antithrombotic agents is being evaluated. Michael W. Mosesson The Blood Center of Southeastern Wisconsin References Mosesson MW. Antithrombin I: inhibition of thrombin generation in plasma by fibrin formation. Thromb Haemost. 2003;89: 9-12.[Medline] [Order article via Infotrieve] Ni H, Papalia JM, Degen JL, Wagner DD. Control of thrombus embolization and fibronectin internalization by integrin alpha IIb beta 3 engagement of the fibrinogen gamma chain. Blood. 2003;102: 3609-3614.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Antibody blockade or mutation of the fibrinogen -chain C-terminus is more effective in inhibiting murine arterial thrombus formation than complete absence of fibrinogen Markéta Jirousková, Igor Chereshnev, Heikki Väänänen, Jay L. Degen, and Barry S. Coller Blood 2004 103: 1995-2002. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mosesson, M. W. Search for Related Content PubMed Articles by Mosesson, M. W. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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