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Neutrophils and Neutrophil Extracellular Traps (NETs) Can Promote Clotting and Impact Clot Structure in a Distinctive Manner

1University of Leeds, Leeds Institute of Cardiovascular and Metabolic Medicine, Discovery and Translational Science Department, Leeds, United Kingdom, 2Wake Forest University, Department of Physics, Winston Salem, NC, United States, 3University of Leeds, The Astbury Centre for Structural Molecular Biology, Molecular & Nanoscale Physics, Leeds, United Kingdom

Abstract Number: PB1950

Meeting: ISTH 2020 Congress

Theme: Vascular Biology » Blood Cells and Vessel Wall

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 mechanical properties, 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 promoted clot formation in pooled normal plasma without the addition of other triggers of coagulation. Both also delayed clot lysis. The procoagulant effect of neutrophils and NETs were also observed in FXII- and FVII-deficient plasma. However, the procoagulant effect of neutrophils was not observed, while NETs still induced clotting, in FXI-deficient plasma. NETs increased the density of clots, particularly in the areas immediately surrounding the NETs, but neutrophils did not. Neutrophil-induced clots were weak and showed large pores. NETs did not significantly affect the average pore size of clots.

Conclusions: NETs accelerate clotting and contribute to the formation of a denser clot architecture. These effects are not mediated through FVII, FXII or FXI but likely involve other components present in the plasma. Neutrophils, or mediators they release, induce clotting via FXI.

To cite this abstract in AMA style:

Shi Y, Baker SR, Gauer JS, Philippou H, Connell SD, Ariens RAS. Neutrophils and Neutrophil Extracellular Traps (NETs) Can Promote Clotting and Impact Clot Structure in a Distinctive Manner [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/neutrophils-and-neutrophil-extracellular-traps-nets-can-promote-clotting-and-impact-clot-structure-in-a-distinctive-manner/. Accessed September 27, 2023.

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