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Citations to this article

Thrombin-mediated activation of factor XI results in a thrombin-activatable fibrinolysis inhibitor-dependent inhibition of fibrinolysis.
P A Von dem Borne, … , M E Nesheim, B N Bouma
P A Von dem Borne, … , M E Nesheim, B N Bouma
Published May 15, 1997
Citation Information: J Clin Invest. 1997;99(10):2323-2327. https://doi.org/10.1172/JCI119412.
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Thrombin-mediated activation of factor XI results in a thrombin-activatable fibrinolysis inhibitor-dependent inhibition of fibrinolysis.

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Abstract

Recently, it has been shown that Factor XI can be activated by thrombin, and that Factor XIa significantly contributes to the generation of thrombin via the intrinsic pathway after the clot has been formed. This additional thrombin, generated inside the clot, was found to protect the clot from fibrinolysis. A plausible mechanism for this inhibitory effect of thrombin involves TAFI (thrombin-activatable fibrinolysis inhibitor, procarboxypeptidase B) which, upon activation, may inhibit fibrinolysis by removing carboxy-terminal lysines from fibrin. We studied the role of Factor XI and TAFI in fibrinolysis using a clot lysis assay. The lysis time was decreased twofold when TAFI was absent, when TAFI activation was inhibited by anti-TAFI antibodies, or when activated TAFI was inhibited by the competitive inhibitor (2-guanidinoethylmercapto)succinic acid. Inhibition of either TAFI activation or Factor XIa exhibited equivalent profibrinolytic effects. In the absence of TAFI, no additional effect of anti-Factor XI was observed on the rate of clot lysis. We conclude that the mechanism of Factor XI-dependent inhibition of fibrinolysis is through the generation of thrombin via the intrinsic pathway, and is dependent upon TAFI. This pathway may play a role in determining the fate of in vivo formed clots.

Authors

P A Von dem Borne, L Bajzar, J C Meijers, M E Nesheim, B N Bouma

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Journal of Thrombosis and Haemostasis 2003
Enhancement of fibrinolytic potential in vitro by anticoagulant drugs targeting activated factor X, but not by those inhibiting thrombin or tissue factor:
T Lisman, J Adelmeijer, HK Nieuwenhuis, PG de Groot
Blood Coagulation & Fibrinolysis 2003
Thrombin and Fibrinolysis
M Nesheim
Chest 2003
Stabilization Versus Inhibition of TAFIa by Competitive Inhibitors in Vitro
JB Walker, B Hughes, I James, P Haddock, C Kluft, L Bajzar
The Journal of biological chemistry 2003
Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life
Mariko Nagashima, Zheng-Feng Yin, Lei Zhao, Kathy White,Yanhong Zhu, Nina Lasky, Meredith Halks-Miller, George J. Broze, Jr., William P. Fay, John Morser
Journal of Clinical Investigation 2002
In Vivo Regulation of the Functions of Plasminogen by Plasma Carboxypeptidase B
Carmen M. Swaisgood, Detlef Schmitt, Dan Eaton, Edward F. Plow
Journal of Clinical Investigation 2002
Paradoxical hyperfibrinolysis is associated with a more intensely haemorrhagic phenotype in severe congenital haemophilia
M Grunewald, A Siegemund, A Grunewald, A Konegen, M Koksch, M Griesshammer
Haemophilia 2002
Overall haemostatic potential can be used for estimation of thrombin-activatable fibrinolysis inhibitor-dependent fibrinolysis in vivo and for possible follow-up of recombinant factor VIIa treatment in patients with inhibitors to factor VIII
JP Antovic, A Antovic, S He, L Tengborn, M Blomback
Haemophilia 2002
Effects of ximelagatran, the oral form of melagatran, in the treatment of caval vein thrombosis in conscious rats
S Carlsson, M Elg, C Mattsson
Thrombosis Research 2002
Enhanced endogenous thrombolysis induced by a specific factor Xa inhibitor, DX-9065a, evaluated in a rat arterial thrombolysis model in vivo
M Hashimoto, Y Onobayashi, K Oiwa, JC Giddings, J Yamamoto
Thrombosis Research 2002
Recombinant factor VIIa improves clot formation but not fibrolytic potential in patients with cirrhosis and during liver transplantation
T Lisman
Hepatology 2002
Studies on the Different Modes of Action of the Anticoagulant Protease Inhibitors DX-9065a and Argatroban: II. EFFECTS ON FIBRINOLYSIS
H Nagashima
The Journal of biological chemistry 2002
The Sepsis Text
JL Vincent, J Carlet, SM Opal
2002
Fast Homogeneous Assay for Plasma Procarboxypeptidase U
KA Schatteman, FJ Goossens, J Leurs, Y Kasahara, SS Scharpé, DF Hendriks
Clinical Chemistry and Laboratory Medicine 2001
Activation of coagulation factor XI, without detectable contact activation in dengue haemorrhagic fever
EC van Gorp, MC Minnema, C Suharti, AT Mairuhu, DP Brandjes, H Cate, CE Hack, JC Meijers
British Journal of Haematology 2001
Factor IX and thrombosis
GD Lowe
British Journal of Haematology 2001
Thrombin-Activatable Fibrinolysis Inhibitor (TAFI, Plasma Procarboxypeptidase B, Procarboxypeptidase R, Procarboxypeptidase U)
BN Bouma, PF Marx, LO Mosnier, JC Meijers
Thrombosis Research 2001
Fisiopatología de la hemostasia. Mecanismos de activación e inhibición. Implicaciones funcionales
RM Díaz, JH Santos, AP Ruiz, VH Linares
Medicine - Programa de Formación Médica Continuada Acreditado 2001
Treatment of Iatrogenic Femoral Pseudoaneurysms with Percutaneous Thrombin Injection: Experience in 54 Patients1
RG Sheiman, DP Brophy
Radiology 2001
Overview of Blood Coagulation
D Green
Hemodialysis International 2001
Coagulation problems in liver disease
SI Rapaport
Blood Coagulation & Fibrinolysis 2000
Role of blood coagulation factor XI in downregulation of fibrinolysis
BN Bouma, JC Meijers
Current Opinion in Hematology 2000
Reduced activity of TAFI (thrombin-activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia
JC Meijers, EJ Oudijk, LO Mosnier, R Bos, BN Bouma, HK Nieuwenhuis, R Fijnheer
British Journal of Haematology 2000
High Levels of Coagulation Factor XI as a Risk Factor for Venous Thrombosis
JC Meijers, WL Tekelenburg, BN Bouma, RM Bertina, FR Rosendaal
New England Journal of Medicine 2000
An Inhibitor of Activated Thrombin-Activatable Fibrinolysis Inhibitor Potentiates Tissue-Type Plasminogen Activator-Induced Thrombolysis in a Rabbit Jugular Vein Thrombolysis Model
M Nagashima, M Werner, M Wang, L Zhao, DR Light, R Pagila, J Morser, P Verhallen
Thrombosis Research 2000
Consequences of inhibition of plasma carboxypeptidase B on in vivo thrombolysis, thrombosis and hemostasis
CJ Refino, L DeGuzman, D Schmitt, R Smyth, S Jeet, MT Lipari, D Eaton, S Bunting
Fibrinolysis and Proteolysis 2000
Tissue factor pathway of coagulation in sepsis:
CE Hack
Critical Care Medicine 2000
Activation of Clotting Factors XI and IX in Patients With Acute Myocardial Infarction
MC Minnema, RJ Peters, R de Winter, YP Lubbers, S Barzegar, KA Bauer, RD Rosenberg, CE Hack, H ten Cate
Arteriosclerosis, thrombosis, and vascular biology 2000
Thrombin Activatable Fibrinolysis Inhibitor and an Antifibrinolytic Pathway
L Bajzar
Arteriosclerosis, thrombosis, and vascular biology 2000
Modulation of hemostatic mechanisms in bacterial infectious diseases
H Tapper, H Herwald
Blood 2000
Identification of a novel mutation in a non-Jewish factor XI deficient kindred
A Alhaq, M Mitchell, M Sethi, S Rahman, G Flynn, P Boulton, G Caeno, M Smith, G Savidge
British Journal of Haematology 1999
TAFI
ME Nesheim
Fibrinolysis and Proteolysis 1999
Activated human protein C prevents thrombin-induced thromboembolism in mice. Evidence that activated protein c reduces intravascular fibrin accumulation through the inhibition of additional thrombin generation
P Gresele, S Momi, M Berrettini, GG Nenci, HP Schwarz, N Semeraro, M Colucci
Journal of Clinical Investigation 1998
Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI. In vivo evidence for a role of factor XI as an anti-fibrinolytic factor
MC Minnema, PW Friederich, M Levi, PA von Borne, LO Mosnier, JC Meijers, BJ Biemond, CE Hack, BN Bouma, H Cate
Journal of Clinical Investigation 1998
Anti-prothrombin antibodies and their relation with thrombosis and lupus anticoagulant
PG Groot, DA Horbach, MJ Simmelink, EV Oort, RH Derksen
Lupus 1998
Both Cellular and Soluble Forms of Thrombomodulin Inhibit Fibrinolysis by Potentiating the Activation of Thrombin-activable Fibrinolysis Inhibitor
L Bajzar, M Nesheim, J Morser, PB Tracy
The Journal of biological chemistry 1998
Activation of Clotting Factor XI Without Detectable Contact Activation in Experimental Human Endotoxemia
MC Minnema, D Pajkrt, WA Wuillemin, D Roem, WK Bleeker, M Levi, SJ van Deventer, CE Hack, H ten Cate
Blood 1998

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