Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots.

Laily D Zubairova,John W Weisel,Chandrasekaran Nagaswami,Yuriy F Zuev,Roza M Nabiullina,Rustem I Litvinov,Ilshat G Mustafin

doi:10.1038/srep17611

Laily D Zubairova, John W Weisel + Show 5 more

Open Access

https://doi.org/10.1038/srep17611

Copy DOI

Abstract

Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1–0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis.

Highlights

Circulating microparticles (MPs) are 0.1–1-μ m-large phospholipid vesicles[1] released from blood and vascular cells upon activation and apoptosis
Despite numerous studies on the association of MPs with various pathological conditions, it is still unclear whether circulating MPs present in the blood of healthy subjects may affect blood clotting and haemostasis, including their impact on the formation and properties of fibrin networks, a major structure and a mechanical scaffold of clots and thrombi
To determine the importance of circulating MPs we used an approach based on elimination of MPs from normal platelet-free plasma (PFP) by filtration, yielding microparticle-depleted plasma (MDP)

Summary

Introduction

Circulating microparticles (MPs) are 0.1–1-μ m-large phospholipid vesicles[1] released from blood and vascular cells upon activation and apoptosis. The question remains open as to whether MPs normally present in blood have a potential to affect haemostasis and can be an additional physiological determinant of the structure and properties of a blood clot determined largely by the fibrin network scaffold. To answer this question, we studied the effects of MPs in vitro on the kinetics of fibrin polymerisation, fibrin network structure and susceptibility to fibrinolysis. The results provide a better understanding of the mechanisms underlying formation of lysis-resistant haemostatic fibrin clots as well as clots and thrombi formed in pathological conditions associated with increased vesiculation of blood and vascular cells

Methods

Results

Conclusion