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Blood, 9 July 2009, Vol. 114, No. 2, pp. 452-458. Prepublished online as a Blood First Edition Paper on April 7, 2009; DOI 10.1182/blood-2009-02-203604. This Article Full Text (PDF) All Versions of this Article: blood-2009-02-203604v1 114/2/452    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 Kravtsov, D. V. Articles by Gailani, D. Search for Related Content PubMed PubMed Citation Articles by Kravtsov, D. V. Articles by Gailani, D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 4, 2009 Accepted March 31, 2009 Factor XI contributes to thrombin generation in the absence of factor XII Dmitri V. Kravtsov, Anton Matafonov, Erik I. Tucker, Mao-fu Sun, Peter N. Walsh, Andras Gruber, and David Gailani* Department of Pathology, Vanderbilt University, Nashville, TN, United States Departments of Science and Engineering and Medicine, Oregon Health and Science University, Portland, OR, United States The Sol Sherry Thrombosis Research Center and the Departments of Biochemistry and Medicine, Temple University School of Medicine, Philadelphia, PA, United States Department of Medicine, Vanderbilt University, Nashville, TN, United States * Corresponding author; email: dave.gailani{at}vanderbilt.edu. During surface-initiated blood coagulation in vitro, activated factor XII (fXIIa) converts factor XI (fXI) to fXIa. While fXI deficiency is associated with a hemorrhagic disorder, factor XII deficiency is not, suggesting fXI can be activated by other mechanisms in vivo. Thrombin activates fXI, and several studies suggest that fXI promotes coagulation independent of fXII. However, a recent study failed to find evidence for fXII-independent activation of fXI in plasma. Using plasma in which fXII is either inhibited or absent, we show that fXI contributes to plasma thrombin generation when coagulation is initiated with low concentrations of tissue factor, factor Xa or -thrombin. The results could not be accounted for by fXIa contamination of the plasma systems. Replacing fXI with recombinant fXI that activates factor IX poorly, or fXI that is activated poorly by thrombin, reduced thrombin generation. An antibody that blocks fXIa activation of factor IX reduced thrombin generation, however, an antibody that specifically interferes with fXI activation by fXIIa did not. The results support a model in which fXI is activated by thrombin or another protease generated early in coagulation, with the resulting fXIa contributing to sustained thrombin generation through activation of factor IX. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Feedback controversy stops here Joost C. M. Meijers Blood 2009 114: 235. [Full Text] [PDF] This article has been cited by other articles: J. C. M. Meijers Feedback controversy stops here Blood, July 9, 2009; 114(2): 235 - 235. [Full Text] [PDF]

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