Polyanions in Coagulation and Thrombosis: Focus on Polyphosphate and Neutrophils Extracellular Traps

Abstract

Neutrophil extracellular traps (NETs) and polyphosphates (polyP) have been recognized as procoagulant polyanions. This review summarizes the activities and regulation of the two procoagulant mediators and compares their functions. NETs are composed of DNA which like polyP is built of phosphate units linked by high-energy phosphoanhydride bonds. Both NETs and polyP form insoluble particulate surfaces composed of a DNA/histone meshwork or Ca²⁺-rich nanoparticles, respectively. These polyanionic molecules modulate coagulation involving an array of mechanisms and trigger thrombosis via activation of the factor XII-driven procoagulant and proinflammatory contact pathway. Here, we outline the current knowledge on NETs and polyP with respect to their procoagulant and prothrombotic nature, strategies for interference of their activities in circulation, as well as the crosstalk between these two molecules. A better understanding of the underlying, cellular mechanisms will shed light on the therapeutic potential of targeting NETs and polyP in coagulation and thrombosis.

Keywords

polyanions - contact activation - NETs - polyP

Authors' Contributions

C.R., H.E., and T.R. wrote the manuscript. All authors edited the manuscript.

^* These two authors contributed equally to this work.

Publication History

Received: 03 October 2020

Accepted: 04 December 2020

Accepted Manuscript online:
11 December 2020

Article published online:
16 February 2021

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