Abstract Number: PB0741
Meeting: ISTH 2020 Congress
Background: Activated platelets play crucial roles on hemostatic responses. They play diverse roles in the fibrinolysis and express of both pro- and anti-fibrinolytic activities. Employing real-time imaging analysis of the platelet-containing plasma clot formation and dissolution, we demonstrated that
1) activated platelets initiated not only coagulation but also fibrinolysis via triggering accumulation of plasminogen and tissue-type plasminogen activator (tPA) on their surface, and that
2) activated platelets attenuated fibrinolysis largely through the activation of thrombin-activatable fibrinolysis inhibitor (TAFI).
Aims: We evaluated how inhibition of coagulation cascade and/or thrombin activity modify TAFI-dependent inhibition of fibrinolysis, using anticoagulants including direct oral anticoagulants; DOACs.
Methods: Employing human platelet-containing plasma, tissue factor-triggering clotting time (CT) and tPA-initiated clot lysis time (CLT) were measured by turbidimetric assay, and these processes together with the accumulation of plasminogen were also visualized by confocal laser scanning microscopy. Thrombin generation during platelet-containing plasma clot formation was determined using fluorogenic substrate of thrombin.
1) In the presence of platelets, CLT was prolonged due to the activation of TAFI, which seemed dependent on the augmented thrombin generation.
2) Both rivaroxaban (activated factor X [FXa] inhibitor) and dabigatran (thrombin inhibitor) at the pharmacological concentration which effectively prolonged CT, similarly shortened CLT, and which were not shortened further by activated TAFI (TAFIa) inhibitor.
3) These two anticoagulants, however, differently modified platelet-associated fibrin network structure and localization of florescent-labeled plasminogen accumulation.
Conclusions: Modulation of the activated platelet-associated thrombin activity largely affected TAFI-dependent regulation of fibrinolysis.
To cite this abstract in AMA style:Suzuki Y, Sano H, Honkura N, Urano T. Modulation of Thrombin Generation or Thrombin Activity on Activated Platelets Surface Largely Affected TAFI-Dependent Regulation of Fibrinolysis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/modulation-of-thrombin-generation-or-thrombin-activity-on-activated-platelets-surface-largely-affected-tafi-dependent-regulation-of-fibrinolysis/. Accessed January 28, 2022.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/modulation-of-thrombin-generation-or-thrombin-activity-on-activated-platelets-surface-largely-affected-tafi-dependent-regulation-of-fibrinolysis/