Fatal dysfunction and disintegration of thrombin-stimulated platelets

Haematologica
Oleg V KimJ W Weisel

Abstract

Platelets play a key role in formation of hemostatic clots and obstructive thrombi as well as in other biological processes. In response to physiological stimulants, including thrombin, platelets change their morphology, express adhesive molecules, undergo aggregation, and secrete bioactive substances, but their subsequent fate is largely unknown. Here we examine late-stage structural, metabolic, and functional consequences of thrombin-induced platelet activation. Using a combination of confocal microscopy, scanning and transmission electron microscopy, flow cytometry, biochemical and biomechanical measurements, we show that thrombin-induced activation is followed by time-dependent platelet dysfunction and disintegration. After ~30 minutes of incubation with thrombin, unlike with collagen or ADP, human platelets underwent disintegration into cellular fragments containing organelles, such as mitochondria, glycogen granules, and vacuoles. Platelet fragmentation was preceded by Ca2+ influx, integrin αIIbβ3 activation and phosphatidylserine exposure (activation phase), followed by mitochondrial depolarization, generation of reactive oxygen species, metabolic ATP depletion and impairment of platelet contractility along with dramatic...Continue Reading

Citations

Mar 22, 2020·Scientific Reports·Irina N ChernyshJohn W Weisel
Apr 11, 2020·International Journal of Molecular Sciences·Elmira R MordakhanovaRustem I Litvinov
Oct 28, 2020·Scientific Reports·Natalia G EvtuginaRustem I Litvinov
Feb 5, 2021·Research and Practice in Thrombosis and Haemostasis·John W Weisel, Rustem I Litvinov
May 11, 2021·Frontiers in Immunology·Etheresia Pretorius
Jul 3, 2021·Metabolites·Rustem I LitvinovJohn W Weisel

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Methods Mentioned

BETA
electron
flow cytometry
confocal microscopy
scanning electron microcopy
electron microscopy
confocal
transmission electron microscopy
flow

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