Localization of Short-Chain Polyphosphate Enhances its Ability to Clot Flowing Blood Plasma

Ju Hun Yeon, Nima Mazinani, Travis S. Schlappi, Karen Y T Chan, James R. Baylis, Stephanie A. Smith, Alexander J. Donovan, Damien Kudela, Galen D. Stucky, Ying Liu, James H. Morrissey, Christian J. Kastrup

Research output: Contribution to journalArticle

Abstract

Short-chain polyphosphate (polyP) is released from platelets upon platelet activation, but it is not clear if it contributes to thrombosis. PolyP has increased propensity to clot blood with increased polymer length and when localized onto particles, but it is unknown whether spatial localization of short-chain polyP can accelerate clotting of flowing blood. Here, numerical simulations predicted the effect of localization of polyP on clotting under flow, and this was tested in vitro using microfluidics. Synthetic polyP was more effective at triggering clotting of flowing blood plasma when localized on a surface than when solubilized in solution or when localized as nanoparticles, accelerating clotting at 10-200 fold lower concentrations, particularly at low to sub-physiological shear rates typical of where thrombosis occurs in large veins or valves. Thus, sub-micromolar concentrations of short-chain polyP can accelerate clotting of flowing blood plasma under flow at low to sub-physiological shear rates. However, a physiological mechanism for the localization of polyP to platelet or vascular surfaces remains unknown.

Original languageEnglish (US)
Article number42119
JournalScientific reports
Volume7
DOIs
StatePublished - Feb 10 2017

ASJC Scopus subject areas

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    Yeon, J. H., Mazinani, N., Schlappi, T. S., Chan, K. Y. T., Baylis, J. R., Smith, S. A., Donovan, A. J., Kudela, D., Stucky, G. D., Liu, Y., Morrissey, J. H., & Kastrup, C. J. (2017). Localization of Short-Chain Polyphosphate Enhances its Ability to Clot Flowing Blood Plasma. Scientific reports, 7, [42119]. https://doi.org/10.1038/srep42119