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The role of thrombin activatable fibrinolysis inhibitor and factor XI in platelet-mediated fibrinolysis resistance: a thromboelastographic study in whole blood.
- Source :
-
Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2011 Jan; Vol. 9 (1), pp. 154-62. - Publication Year :
- 2011
-
Abstract
- Background: The resistance of platelet-rich thrombi to fibrinolysis is generally attributed to clot retraction and platelet PAI-1 release. The role of TAFI in platelet-mediated resistance to lysis is unclear.<br />Objective: We investigated the contribution of TAFI to the antifibrinolytic effect of platelets in whole blood by thromboelastography.<br />Methods: Platelet-poor (PP-WB, < 40 × 10(3) μL(-1) ) and platelet-rich (PR-WB, > 400 × 10(3) μL(-1) ) blood samples were obtained from normal human blood (N-WB, 150-220 × 10(3) μL(-1) ). Clot lysis time was measured by thromboelastography in recalcified blood supplemented with t-PA (100 ng mL(-1) ) and tissue factor (1:1000 Recombiplastin).<br />Results: t-PA-induced lysis time increased in parallel with platelet concentration (up to 3-fold). Neutralization of TAFI, but not of PAI-1, shortened the lysis time by ∼ 50% in PR-WB and by < 10% in PP-WB. Accordingly, prothrombin F1+2 and TAFIa accumulation was greater in PR-WB than in PP-WB. A similar TAFI-dependent inhibition of fibrinolysis was observed when clot retraction was prevented by cytochalasin D or abciximab, or when platelet membranes were tested. Moreover, in blood with an intact contact system, platelet-mediated fibrinolysis resistance was attenuated by an anti-FXI but not by an anti F-XII antibody. Finally, platelets made the clots resistant to the profibrinolytic effect of heparin concentrations displaying a strong anticoagulant activity.<br />Conclusions: Our data indicate that TAFI activation is one major mechanism whereby platelets make clots resistant to fibrinolysis and underscore the importance of TAFI inhibitors as new antithrombotic agents.<br /> (© 2010 International Society on Thrombosis and Haemostasis.)
- Subjects :
- Abciximab
Antibodies, Monoclonal pharmacology
Anticoagulants pharmacology
Blood Platelets drug effects
Cytochalasin D pharmacology
Heparin pharmacology
Humans
Immunoglobulin Fab Fragments pharmacology
Peptide Fragments blood
Plasminogen Activator Inhibitor 1 blood
Platelet Aggregation Inhibitors pharmacology
Prothrombin
Thromboplastin metabolism
Time Factors
Tissue Plasminogen Activator blood
Blood Platelets metabolism
Carboxypeptidase B2 blood
Factor XI metabolism
Fibrinolysis drug effects
Thrombelastography
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7836
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and haemostasis : JTH
- Publication Type :
- Academic Journal
- Accession number :
- 20961395
- Full Text :
- https://doi.org/10.1111/j.1538-7836.2010.04120.x