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.
P A Von dem Borne, L Bajzar, J C Meijers, M E Nesheim, B N Bouma
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Blood Coagulation & Fibrinolysis | 2006 |
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Journal of Thrombosis and Haemostasis | 2006 |
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Thrombosis Research | 2006 |
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Mechanism of action, development and clinical experience of recombinant FVIIa
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Journal of Thrombosis and Haemostasis | 2005 |
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Studies in Multidisciplinarity
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Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis
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Blood | 2005 |
Tissue factor and tissue factor pathway inhibitor
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Anaesthesia | 2004 |
New insights into factors affecting clot stability: a role for thrombin activatable fibrinolysis inhibitor (TAFI; plasma procarboxypeptidase B, plasma procarboxypeptidase U, procarboxypeptidase R)
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Seminars in Hematology | 2004 |
Does an enzyme other than thrombin contribute to unexpected changes in the levels of the different forms of thrombin activatable fibrinolysis inhibitor in patients with hemophilia A, hemophilia B and von Willebrand disease?
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Scandinavian Journal of Clinical & Laboratory Investigation | 2004 |
Hyperprothrombinemia associated with prothrombin G20210A mutation inhibits plasma fibrinolysis through a TAFI-mediated mechanism
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Blood | 2004 |
Thrombin-activatable fibrinolysis inhibitor and the risk for recurrent venous thromboembolism
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Blood | 2004 |
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Journal of Thrombosis and Haemostasis | 2003 |
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BN Bouma, JC Meijers |
Journal of Thrombosis and Haemostasis | 2003 |
Thrombin Activatable Fibrinolysis Inhibitor (TAFI) at the Interface between Coagulation and Fibrinolysis
BN Bouma, LO Mosnier |
Pathophysiology of Haemostasis and Thrombosis | 2003 |
Inherited factor XI deficiency confers no protection against acute myocardial infarction
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Journal of Thrombosis and Haemostasis | 2003 |
Eptifibatide-induced thrombocytopenia and coronary bypass operation
KA Tanaka, JD Vega, AB Kelly, SR Hanson, JH Levy |
Journal of Thrombosis and Haemostasis | 2003 |
Perioperative topical bovine thrombin exposure is not associated with hemodialysis graft thrombosis
MD Vannorsdall, YS Arkel, DH Ku, FL Lucas, J Himmelfarb |
Kidney International | 2003 |
Plasmatic coagulation and fibrinolytic system alterations in PNH
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Blood Coagulation & Fibrinolysis | 2003 |
Rebuttal to: Effect of heparin on TAFI-dependent inhibition of fibrinolysis
T Lisman, PG de Groot |
Journal of Thrombosis and Haemostasis | 2003 |
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Blood Coagulation & Fibrinolysis | 2003 |
Thrombin and Fibrinolysis
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The Journal of biological chemistry | 2003 |
Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life
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Journal of Clinical Investigation | 2002 |
In Vivo Regulation of the Functions of Plasminogen by Plasma Carboxypeptidase B
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Journal of Clinical Investigation | 2002 |
Paradoxical hyperfibrinolysis is associated with a more intensely haemorrhagic phenotype in severe congenital haemophilia
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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 |