Circulating Microparticles Alter Formation, Structure and Properties of Fibrin Clots

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.

Ticagrelor attenuates the increase of extracellular vesicle concentrations in plasma after acute myocardial infarction compared to clopidogrel

“…43 Further, scanning electron microscopy revealed that thrombi expose 0.1-0.5 μm in diameter, granular and CD61-positive particles, suggesting that platelet EVs adhere to fibrin. 44,45 Incorporation of EVs in thrombi in the acute phase of AMI may result in a lower concentration of platelet EVs in systemic blood.…”

Blood clot contraction differentially modulates internal and external fibrinolysis

“…The outcomes were remarkably different when the effect of contraction on internal lysis was modeled by adding t‐PA prior to initiating clotting in order to recapitulate the physiological sequence of reactions . The concentration of t‐PA added (75 ng mL −1 ) did not initiate lysis until after the clot had been completely formed, as confirmed by a kinetic turbidimetry assay (Figure S4).…”

Fibrin Formation, Structure and Properties

“…Fibrin structure and properties are greatly influenced by the presence of blood cells, namely activated platelets and erythrocytes (Aleman et al 2014; Malecki et al 2015) that form a natural and very active environment for clot formation. In addition to whole cells, the effects of circulating cell-derived microparticles on the fibrin clot structure and properties have been recently demonstrated (Zubairova et al 2015). Fibrin can interact with other components of the extracellular matrix, both filamentous and non-filamentous, that not only affects fibrin structure but imparts additional mechanical and chemical stability (Maquart and Monboisse 2014).…”