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. Objective: We investigated the contribution of TAFI to the antifibrinolytic effect of platelets in whole blood by thromboelastography. Methods: Platelet-poor (PP-WB, < 40 x 103 µL-1) and platelet-rich (PR-WB, > 400 x 103 µL-1) blood samples were obtained from normal human blood (N-WB, 150-220 x 103 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). Results: t-PA-induced lysis time increased in parallel to 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. 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.

Autore Pugliese

• Colucci Mario

Tutti gli autori

• COLUCCI M.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2011

ISSN

1538-7933

ISBN

Non Disponibile

Numero di citazioni Wos

32

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

34

Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

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