Microparticles: new light shed on the understanding of venous thromboembolism

Zhou, Lin; Qi, Xiaolong; Xu, Mingxin; Yu, Mengxiao; Liu, Ming-Lin; Song, Haoming

doi:10.1038/aps.2014.73

Cited by 29 publications

(21 citation statements)

References 94 publications

(113 reference statements)

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“…The increased incidence of venous thrombosis throughout the course of GBM has been well documented (38). In fact, the elevated levels of circulating MVs in cancer patients has been correlated with thrombosis in a number of cancer types (9,11,30). However, it has previously been demonstrated that elevated levels of TF-positive MVs do not correlate with thrombosis occurrence in patients with GBM (39).…”

Section: Discussionmentioning

confidence: 99%

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Hypoxia regulates the expression of tissue factor pathway signaling elements in a rat glioma model

et al. 2016

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Abstract. Hypoxia and necrosis are fundamental features of glioma, and their emergence is critical for the rapid biological progression of this fatal tumor. The presence of vaso-occlusive thrombus is higher in grade IV tumors [glioblastoma multiforme (GBM)] compared with lower grade tumors, suggesting that the procoagulant properties of the tumor contribute to its aggressive behavior, as well as the establishment of tumor hypoxia and necrosis. Tissue factor (TF), the primary cellular initiator of coagulation, is overexpressed in GBMs and likely favors a thrombotic microenvironment. Phosphatase and tensin homolog (PTEN) loss and hypoxia are two common alterations observed in glioma that may be responsible for TF upregulation. In the present study, ST1 and P7 rat glioma lines, with different levels of aggressiveness, were comparatively analyzed with the aim of identifying differences in procoagulant mechanisms. The results indicated that P7 cells display potent procoagulant activity compared with ST1 cells. Flow cytometric analysis showed less pronounced levels of TF in ST1 cells compared with P7 cells. Notably, P7 cells supported factor X (FX) activation via factor VIIa, whereas no significant FXa generation was observed in ST1 cells. Furthermore, the exposure of phosphatidylserine on the surface of P7 and ST1 cells was investigated. The results supported the assembly of prothrombinase complexes, accounting for the production of thrombin. Furthermore, reverse transcription-quantitative polymerase chain reaction showed that CoCl 2 (known to induce a hypoxic-like stress) led to an upregulation of TF levels in P7 and ST1 cells. Therefore, increased TF expression in P7 cells was accompanied by increased TF procoagulant activity. In addition, hypoxia increased the shedding of procoagulant TF-bearing microvesicles in both cell lines. Finally, hypoxic stress induced by treatment with CoCl 2 upregulated the expression of the PAR1 receptor in both P7 and ST1 cells. In addition to PAR1, P7, but not ST1 cells, expressed higher levels of PAR2 under hypoxic stress. Thus, modulating these molecular interactions may provide additional insights for the development of more efficient therapeutic strategies against aggressive glioma.

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Section: Discussionmentioning

confidence: 99%

“…Increased TF expression has been also associated with cancer-associated thrombosis, a highly relevant systemic response (8,9). In fact, several studies suggest that circulating extracellular vesicles containing TF may be important in a patient's prothrombotic state (10,11).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia regulates the expression of tissue factor pathway signaling elements in a rat glioma model

et al. 2016

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“…Further, although rates of VTE are heavily debated, autopsies have shown pulmonary embolism (PE) rates up to 35% (38) and PE-related mortality rates as high as 40% (11). Microparticles are known contributors to hypercoagulability in various disease processes (18, 19, 39), and previous research has demonstrated that PMPs are associated with increased procoagulant activity in fresh frozen plasma (40) and are associated with hypercoagulability in other injury models (22). The current study is the first to highlight the link between PMPs and coagulation in burns and future burn care may require targeted anticoagulation strategies based on the time course after injury, including use of agents that target platelets and PMPs specifically, to more effectively prevent thrombosis-related morbidity and mortality.…”

Section: Discussionmentioning

confidence: 99%

Impact of Platelets and Platelet-Derived Microparticles on Hypercoagulability Following Burn Injury

Kuethe

Rice

Veile

et al. 2016

Shock

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An acute burn induced coagulopathy develops after scald injury, which evolves into a subacute, hypercoagulable state. Microparticles, specifically platelet-derived MPs (PMPs), have been suggested as possible contributors. We first developed a model of burn-induced coagulopathy and then sought to investigate the role of platelets and PMPs in coagulation after burn. We hypothesized that changes in circulating platelet and PMP populations after injury would contribute to the post-burn, hypercoagulable state. A murine scald model with 28% TBSA full thickness burn injury was utilized and blood samples were collected at intervals after injury. Circulating MP populations, platelet counts, overall coagulation, and platelet function were determined. Burn injury led to hypercoagulability on post-burn day one (PBD1), which persisted 6 days after injury (PBD6). On PBD1, there was a significant decrease in platelet numbers and a decline in platelet contribution to clot formation with a concomitant increase in circulating procoagulant PMPs. On PBD6, there was a significant increase in platelet numbers and in platelet activation with no change in PMPs compared with sham. Further, on PBD1 decreased ADP-induced platelet activation was observed with a contrasting increase in ADP-induced platelet activation on PBD6. We therefore concluded that there was a temporal change in the mechanisms leading to a hypercoagulable state after scald injury, that PMPs are responsible for changes seen on PBD1, and finally that ADP-induced platelet activation was key to the augmented clotting mechanisms 6 days after burn.

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“…Most of these conditions are characterized by a hypercoagulable state, which may lead to venous thrombosis. Indeed, the direct link between MPs and VTE is supported by a considerable amount of new evidence [24,25,27]. MPs may become in the future one of the novel biomarkers for early primary and/or secondary VTE prevention protocols [28].…”

Section: Introductionmentioning

confidence: 99%

Modulating thrombotic diathesis in hereditary thrombophilia and antiphospholipid antibody syndrome: a role for circulating microparticles?

Campello

Radu

Spiezia

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Over the past decades, there have been great advances in the understanding of the pathogenesis of venous thromboembolism (VTE) in patients with inherited and acquired thrombophilia [mainly antiphospholipid antibody syndrome (APS)]. However, a number of questions remain unanswered. Prognostic markers capable of estimating the individual VTE risk would be of great use. Microparticles (MPs) are sub-micron membrane vesicles constitutively released from the surface of cells after cellular activation and apoptosis. The effects of MPs on thrombogenesis include the exposure of phopshatidylserine and the expression of tissue factor and MPs have been described in clinical studies as possible diagnostic and prognostic biomarkers for VTE. This review will provide a novel perspective on the current knowledge and research trends on the possible role of MPs in hereditary thrombophilia and APS. Basically, the published data show that circulating MPs may contribute to the development of VTE in thrombophilic carriers, both in mild and severe states. Moreover, the presence of endothelial-MPs and plateletMPs has been described in antiphospholipid syndrome and seems to be directly linked to antiphospholipid antibodies and not to other underlying autoimmune disorders or the thrombotic event itself. In conclusion, circulating MPs may constitute an epiphenomenon of thrombophilia itself and could be up-regulated in acute particular conditions, promoting a global prothrombotic state up to the threshold of the clinical relevant thrombotic event.

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Microparticles: new light shed on the understanding of venous thromboembolism

Cited by 29 publications

References 94 publications

Hypoxia regulates the expression of tissue factor pathway signaling elements in a rat glioma model

Hypoxia regulates the expression of tissue factor pathway signaling elements in a rat glioma model

Impact of Platelets and Platelet-Derived Microparticles on Hypercoagulability Following Burn Injury

Modulating thrombotic diathesis in hereditary thrombophilia and antiphospholipid antibody syndrome: a role for circulating microparticles?

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