Abstract Number: PB0118
Meeting: ISTH 2021 Congress
Background: Neutrophils release mediators (e.g. matrix metalloproteinases and serine proteases) which can influence thrombus formation. Neutrophil Extracellular Traps (NETs), which are extruded from neutrophils, have been shown to provide a “scaffold” for thrombosis and to increase the resistance of clots to fibrinolysis and thrombolysis. However, the interactions between neutrophils or NETs and fibrin(ogen) in clots, as well as the mechanisms behind these interactions are not yet fully understood.
Aims: To investigate the role of neutrophils/NETs in blood coagulation, fibrin formation, clot stability and clot porosity, in order to decipher how neutrophils/NETs interact with the fibrin network.
Methods: Human neutrophils were isolated from whole blood by the standard density gradient centrifugation method. Neutrophils were stimulated by Phorbol 12-myristate 13-acetate to generate NETs. Turbidity measurements were used to measure the kinetics of clot formation. Confocal microscopy was used to investigate the effects of neutrophils/NETs on overall clot network structure. Permeation experiments were carried out to investigate clot porosity.
Results: Neutrophils and NETs promote clotting in plasma without the addition of other coagulation triggers, but not in purified fibrinogen, indicating that other factors mediate the interaction. Both neutrophils and NETs also delayed clot lysis in plasma. The procoagulant effects of neutrophils and NETs were also observed in FXII- and FVII-deficient plasma. In FXI-deficient plasma, only the procoagulant effects of NETs were observed, but not of neutrophils. NETs increased the density of clots, particularly in the vicinity of the NETs, while neutrophils-induced clots were less stable and more porous.
Conclusions: NETs accelerate clotting and contribute to the formation of a denser clot architecture that is more resistant to lysis. Neutrophils, or their released mediators, may induce clotting in a different manner to NETs, mediated by FXI.
To cite this abstract in AMA style:Shi Y, Gauer JS, Baker SR, Philippou H, Connell SD, Ariëns RAS. Neutrophils Can Promote Clotting by Secreting Proteins that Activate FXI while NETs Promote Clotting Independently of FXI in vitro [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/neutrophils-can-promote-clotting-by-secreting-proteins-that-activate-fxi-while-nets-promote-clotting-independently-of-fxi-in-vitro/. Accessed December 2, 2022.
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