This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oliver, J. A. Articles by Hoffman, M. Search for Related Content PubMed PubMed Citation Articles by Oliver, J. A. Articles by Hoffman, M. Related Collections Coagulation and fibronolysis Platelets

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:170-177.)
© 1999 American Heart Association, Inc.

Original Contributions

Thrombin Activates Factor XI on Activated Platelets in the Absence of Factor XII

Julie A. Oliver; Dougald M. Monroe; Harold R. Roberts; Maureane Hoffman

From the Department of Medicine and Center for Thrombosis and Hemostasis, University of North Carolina, Chapel Hill (J.A.O., D.M.M., H.R.R., M.H.), and the Department of Pathology, Durham Veterans Affairs Medical Center and Duke University, Durham (J.A.O., M.H.), NC.

Correspondence to Maureane Hoffman, MD, PhD, Laboratory Service (113), Durham VA Medical Center, 508 Fulton St, Durham, NC 27705. E-mail maureane{at}med.unc.edu

Abstract—Thrombin can activate factor XI in the presence of dextran sulfate or sulfatides. However, a physiological cofactor for thrombin activation of factor XI has not been identified. We examined this question in a cell-based, tissue factor–initiated model system. In the absence of factor XII, factor XI enhanced thrombin generation in this model. The effect on thrombin generation was reproduced by 2 to 5 pmol/L factor XIa. A specific inhibitor of factor XIIa did not diminish the effect of factor XI. Thus, factor XI can be activated in a model system that does not contain factor XIIa or nonphysiological cofactors. Preincubation of factor XI with activated platelets and thrombin or factor Xa enhanced subsequent thrombin generation in the model system. Preincubation of factor XI with thrombin or factor Xa, but without platelets, did not enhance thrombin generation, suggesting that these proteases might activate factor XI on platelet surfaces. Thrombin and factor Xa were then directly tested for their ability to activate factor XI. In the presence of dextran sulfate, thrombin or factor Xa activated factor XI. Thrombin, but not factor Xa, also cleaved detectable amounts of factor XI in the presence of activated platelets. Thus, thrombin activates enough factor XI to enhance subsequent thrombin generation in a model system. Platelet surfaces might provide the site for thrombin activation of functionally significant amounts of factor XI in vivo.

Key Words: factor XIa • factor XIIa • factor IXa • human blood coagulation • contact system

This article has been cited by other articles:

				D. V. Kravtsov, A. Matafonov, E. I. Tucker, M.-f. Sun, P. N. Walsh, A. Gruber, and D. Gailani Factor XI contributes to thrombin generation in the absence of factor XII Blood, July 9, 2009; 114(2): 452 - 458. [Abstract] [Full Text] [PDF]

				G. Romney and M. Glick An Updated Concept of Coagulation With Clinical Implications J Am Dent Assoc, May 1, 2009; 140(5): 567 - 574. [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]

				D. M. Monroe and M. Hoffman What Does It Take to Make the Perfect Clot? Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 41 - 48. [Abstract] [Full Text] [PDF]

				C. L. Kempton, M. Hoffman, H. R. Roberts, and D. M. Monroe Platelet Heterogeneity: Variation in Coagulation Complexes on Platelet Subpopulations Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 861 - 866. [Abstract] [Full Text] [PDF]

				N. Mackman Role of Tissue Factor in Hemostasis, Thrombosis, and Vascular Development Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1015 - 1022. [Abstract] [Full Text] [PDF]

				A. S. Wolberg, D. M. Monroe, H. R. Roberts, and M. Hoffman Elevated prothrombin results in clots with an altered fiber structure: a possible mechanism of the increased thrombotic risk Blood, April 15, 2003; 101(8): 3008 - 3013. [Abstract] [Full Text] [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]

				A. Zivelin, F. Bauduer, L. Ducout, H. Peretz, N. Rosenberg, R. Yatuv, and U. Seligsohn Factor XI deficiency in French Basques is caused predominantly by an ancestral Cys38Arg mutation in the factor XI gene Blood, April 1, 2002; 99(7): 2448 - 2454. [Abstract] [Full Text] [PDF]

				J. C.M. Meijers, W. L.H. Tekelenburg, B. N. Bouma, R. M. Bertina, and F. R. Rosendaal High Levels of Coagulation Factor XI as a Risk Factor for Venous Thrombosis N. Engl. J. Med., March 9, 2000; 342(10): 696 - 701. [Abstract] [Full Text] [PDF]

				D. L. French and U. Seligsohn Platelet Glycoprotein IIb/IIIa Receptors and Glanzmann’s Thrombasthenia Arterioscler Thromb Vasc Biol, March 1, 2000; 20(3): 607 - 610. [Full Text] [PDF]

				F. A. Baglia and P. N. Walsh Thrombin-mediated Feedback Activation of Factor XI on the Activated Platelet Surface Is Preferred over Contact Activation by Factor XIIa or Factor XIa J. Biol. Chem., June 30, 2000; 275(27): 20514 - 20519. [Abstract] [Full Text] [PDF]