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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 Butenas, S. Articles by Mann, K. G. Search for Related Content PubMed PubMed Citation Articles by Butenas, S. Articles by Mann, K. G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 February 2002, Vol. 99, No. 3, pp. 923-930 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Mechanism of factor VIIa-dependent coagulation in hemophilia blood Saulius Butenas, Kathleen E. Brummel, Richard F. Branda, Sara G. Paradis, and Kenneth G. Mann From the University of Vermont, College of Medicine, Burlington. The ability of factor VIIa to initiate thrombin generation and clot formation in blood from healthy donors, blood from patients with hemophilia A, and in anti-factor IX antibody-induced ("acquired") hemophilia B blood was investigated. In normal blood, both factor VIIa-tissue factor (TF) complex and factor VIIa alone initiated thrombin generation. The efficiency of factor VIIa was about 0.0001 that of the factor VIIa-TF complex. In congenital hemophilia A blood and "acquired" hemophilia B blood in vitro, addition of 10 to 50 nM factor VIIa (pharmacologic concentrations) corrected the clotting time at all TF concentrations tested (0-100 pM) but had little effect on thrombin generation. Fibrinopeptide release and insoluble clot formation were only marginally influenced by addition of factor VIIa. TF alone had a more pronounced effect on thrombin generation; an increase in TF from 0 to 100 pM increased the maximum thrombin level in "acquired" hemophilia B blood from 120 to 480 nM. Platelet activation was considerably enhanced by addition of factor VIIa to both hemophilia A blood and "acquired" hemophilia B blood. Thus, pharmacologic concentrations of factor VIIa cannot restore normal thrombin generation in hemophilia A and hemophilia B blood in vitro. The efficacy of factor VIIa (10-50 nM) in hemophilia blood is dependent on TF. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Platelet-dependent action of high-dose factor VIIa Maureane Hoffman, Dougald M. Monroe, Harold R. Roberts, Kenneth G. Mann, and Saulius Butenas Blood 2002 100: 364-366. [Full Text] [PDF] This article has been cited by other articles: L. J. Bowman, W. E. Uber, M. R. Stroud, L. R. Christiansen, J. Lazarchick, A. J. Crumbley III, J. M. Kratz, J. M. Toole, F. A. Crawford Jr, and J. S. Ikonomidis Use of Recombinant Activated Factor VII Concentrate to Control Postoperative Hemorrhage in Complex Cardiovascular Surgery. Ann. Thorac. Surg., May 1, 2008; 85(5): 1669 - 1677. [Abstract] [Full Text] [PDF] T. Orfeo, K. E. Brummel-Ziedins, M. Gissel, S. Butenas, and K. G. Mann The Nature of the Stable Blood Clot Procoagulant Activities J. Biol. Chem., April 11, 2008; 283(15): 9776 - 9786. [Abstract] [Full Text] [PDF] F. Szlam, T. Taketomi, C. A. Sheppard, C. L. Kempton, J. H. Levy, and K. A. Tanaka Antithrombin Affects Hemostatic Response to Recombinant Activated Factor VII in Factor VIII Deficient Plasma Anesth. Analg., March 1, 2008; 106(3): 719 - 724. [Abstract] [Full Text] [PDF] N. Mackman, R. E. Tilley, and N. S. Key Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1687 - 1693. [Abstract] [Full Text] [PDF] P. M. Mannucci and M. Levi Prevention and Treatment of Major Blood Loss N. Engl. J. Med., May 31, 2007; 356(22): 2301 - 2311. [Full Text] [PDF] G. A. Allen, E. Persson, R. A. Campbell, M. Ezban, U. Hedner, and A. S. Wolberg A Variant of Recombinant Factor VIIa With Enhanced Procoagulant and Antifibrinolytic Activities in an In Vitro Model of Hemophilia Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): 683 - 689. [Abstract] [Full Text] [PDF] K. A. O'Connell, J. J. Wood, R. P. Wise, J. N. Lozier, and M. M. Braun Thromboembolic Adverse Events After Use of Recombinant Human Coagulation Factor VIIa JAMA, January 18, 2006; 295(3): 293 - 298. [Abstract] [Full Text] [PDF] A. D. Ma and D. Carrizosa Acquired Factor VIII Inhibitors: Pathophysiology and Treatment Hematology, January 1, 2006; 2006(1): 432 - 437. [Abstract] [Full Text] [PDF] T. Orfeo, S. Butenas, K. E. Brummel-Ziedins, and K. G. Mann The Tissue Factor Requirement in Blood Coagulation J. Biol. Chem., December 30, 2005; 280(52): 42887 - 42896. [Abstract] [Full Text] [PDF] V. B. Louvain-Quintard, E. P. Bianchini, C. Calmel-Tareau, M. Tagzirt, and B. F. Le Bonniec Thrombin-activable Factor X Re-establishes an Intrinsic Amplification in Tenase-deficient Plasmas J. Biol. Chem., December 16, 2005; 280(50): 41352 - 41359. [Abstract] [Full Text] [PDF] H. R. Roberts, D. M. Monroe, and G. C. White The use of recombinant factor VIIa in the treatment of bleeding disorders Blood, December 15, 2004; 104(13): 3858 - 3864. [Abstract] [Full Text] [PDF] T. Lisman, J. Adelmeijer, H. F. G. Heijnen, and P. G. de Groot Recombinant factor VIIa restores aggregation of {alpha}IIb{beta}3-deficient platelets via tissue factor-independent fibrin generation Blood, March 1, 2004; 103(5): 1720 - 1727. [Abstract] [Full Text] [PDF] M. Tranholm, K. Kristensen, A. T. Kristensen, C. Pyke, R. Rojkjaer, and E. Persson Improved hemostasis with superactive analogs of factor VIIa in a mouse model of hemophilia A Blood, November 15, 2003; 102(10): 3615 - 3620. [Abstract] [Full Text] [PDF] K. G. Mann Thrombin Formation Chest, September 1, 2003; 124(3_suppl): 4S - 10S. [Abstract] [Full Text] [PDF] V. N. Naik, C. D. Mazer, D. A. Latter, J. M. Teitel, and G. M.T. Hare Successful treatment using recombinant factor VIIa for severe bleeding post cardiopulmonary bypass: [La reussite d'un traitement avec le facteur VIIa recombinant pour un saignement abondant apres la circulation extracorporelle] Can J Anesth, June 1, 2003; 50(6): 599 - 602. [Abstract] [Full Text] [PDF] D. M. Monroe and H. R. Roberts Mechanism of Action of High-Dose Factor VIIa: Points of Agreement and Disagreement Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 8 - 9. [Full Text] [PDF] K. G. Mann and S. Butenas Response: Mechanism of Action of High-Dose Factor VIIa Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 10 - 10. [Full Text] [PDF] K. G. Mann, S. Butenas, and K. Brummel The Dynamics of Thrombin Formation Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 17 - 25. [Abstract] [Full Text] [PDF] S. Butenas, K. E. Brummel, S. G. Paradis, and K. G. Mann Influence of Factor VIIa and Phospholipids on Coagulation in "Acquired" Hemophilia Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 123 - 129. [Abstract] [Full Text] [PDF] K. G. Mann and M. Kalafatis Factor V: a combination of Dr Jekyll and Mr Hyde Blood, January 1, 2003; 101(1): 20 - 30. [Full Text] [PDF] S. R. Deitcher, T. L. Carman, and K. Kottke-Marchant Simultaneous Deep Venous Thrombosis and Acquired Factor VIII Inhibitor Clinical and Applied Thrombosis/Hemostasis, October 1, 2002; 8(4): 375 - 379. [Abstract] [PDF] D. M. Monroe, M. Hoffman, and H. R. Roberts Platelets and Thrombin Generation Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1381 - 1389. [Abstract] [Full Text] [PDF] M. Hoffman, D. M. Monroe, H. R. Roberts, K. G. Mann, and S. Butenas Platelet-dependent action of high-dose factor VIIa Blood, June 17, 2002; 100(1): 364 - 366. [Full Text] [PDF]

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