Platelets and Platelet‐Derived Extracellular Vesicles in Liver Physiology and Disease

Balaphas, Alexandre; Meyer, Jérémy; Sadoul, Karin; Fontana, Pierre; Morel, Philippe; Gonelle‐Gispert, Carmen; Bühler, Léo H.

doi:10.1002/hep4.1358

Cited by 28 publications

(22 citation statements)

References 139 publications

(266 reference statements)

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“…Thrombocytopenia is also compensated by the presence of platelet-derived extracellular vesicles (EV); microparticles (0.1–1 μm) which are highly pro-coagulant and contribute to ongoing activation of coagulation ( 23 ). Recently a study by Stravitz et al showed that patients suffering from acute liver failure had an increased amount of these circulating microparticles ( 23 , 24 ).…”

Section: Rebalanced Hemostasismentioning

confidence: 99%

“…In summary, contrary to the common belief that acute liver failure patients are “autoanticoagulated,” they may be more prone to thrombosis rather than bleeding. There is a combination of (a) thrombocytopenia compensated with elevated levels of vWF, factor VIII and reduced ADAMTS-13, (b) a hypofibrinolytic state due to elevated PAI-1 and low plasminogen, and (c) elevated levels of pro-coagulant microparticles that may all lead to an increased risk of thrombosis and worsen outcome ( 23 , 24 ).…”

Section: Rebalanced Hemostasismentioning

confidence: 99%

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Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies

2020

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Pediatric Acute Liver Failure (PALF) is a rapidly progressive clinical syndrome encountered in the pediatric ICU which may rapidly progress to multi-organ dysfunction, and on occasion to life threatening cerebral edema and hemorrhage. Pediatric Acute Liver Failure is defined as severe acute hepatic dysfunction accompanied by encephalopathy and liver-based coagulopathy defined as prolongation of International Normalized Ratio (INR) >1.5. However, coagulopathy in PALF is complex and warrants a deeper understanding of the hemostatic balance in acute liver failure. Although an INR value of >1.5 is accepted as the evidence of coagulopathy and has historically been viewed as a prognostic factor of PALF, it may not accurately reflect the bleeding risk in PALF since it only measures procoagulant factors. Paradoxically, despite the prolongation of INR, bleeding risk is lower than expected (around 5%). This is due to “rebalanced hemostasis” due to concurrent changes in procoagulant, anticoagulant and fibrinolytic systems. Since the liver is involved in both procoagulant (Factors II, V, IX, XI, and fibrinogen) and anticoagulant (Protein C, Protein S, and antithrombin) protein synthesis, PALF results in “rebalanced hemostasis” or even may shift toward a hypercoagulable state. In addition to rebalanced coagulation there is altered platelet production due to decreased thrombopoietin production by liver, increased von Willebrand factor from low grade endothelial cell activation, and hyperfibrinolysis and dysfibrinogenemia from altered synthetic liver dysfunction. All these alterations contribute to the multifactorial nature of coagulopathy in PALF. Over exuberant use of prophylactic blood products in patients with PALF may contribute to morbidities such as fluid overload, transfusion-associated lung injury, and increased thrombosis risk. It is essential to use caution when using INR values for plasma and factor administration. In this review we will summarize the complexity of coagulation in PALF, explore “rebalanced hemostasis,” and discuss the limitations of current coagulation tests. We will also review strategies to accurately diagnose the coagulopathy of PALF and targeted therapies.

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Section: Rebalanced Hemostasismentioning

confidence: 99%

Section: Rebalanced Hemostasismentioning

confidence: 99%

Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies

2020

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“…Platelet-derived EVs are primarily characterised by the presence of CD41, CD42b and phosphatidylserine and have been demonstrated to play roles in exercise [27, 28], acute injury [29] and diabetes [30]. Platelet-derived EVs are regarded as the most abundant source of plasma EVs; however, it is unclear as to what proportion of the EV pool they represent, with approximations varying from 50 to 90% [29]. Platelet EV release is calcium dependent and relies on actin cytoskeleton destabilisation [31].…”

Section: Evs As Biomarkers Of Metabolic Diseasementioning

confidence: 99%

Extracellular vesicles in metabolic disease

et al. 2019

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Extracellular vesicles (EVs) are submicron-sized lipid envelopes that are produced and released from a parent cell and can be taken up by a recipient cell. EVs are capable of mediating cellular signalling by carrying nucleic acids, proteins, lipids and cellular metabolites between cells and organs. Metabolic dysfunction is associated with changes in plasma concentrations of EVs as well as alterations in their EV cargo. Since EVs can act as messengers between parent and recipient cells, they could be involved in cell-to-cell and organ-to-organ communication in metabolic diseases. Recent literature has shown that EVs are produced by cells within metabolic tissues, such as adipose tissue, pancreas, muscle and liver. These vesicles have therefore been proposed as a novel intercellular communication mode in systemic metabolic regulation. In this review, we will describe and discuss the current literature that investigates the role of adipose-derived EVs in the regulation of obesity-associated metabolic disease. We will particularly focus on the EV-dependent communication between adipocytes, the vasculature and immune cells in type 2 diabetes.Electronic supplementary materialThe online version of this article (10.1007/s00125-019-05014-5) contains a slide of the figure for download, which is available to authorised users.

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“…Furthermore, to add complexity, EVs can also be secreted from other cells and influence liver inflammation. In this regard, some evidence suggests that platelet-derived EVs may have proinflammatory effects in the liver, but this needs further confirmation [39,40]. Finally, it has also been shown that EVs are released from monocytic cells and induce polarization towards the anti-inflammatory M2 phenotype of neighboring naive monocytes by delivering cargo miR-27a, thus contributing to resolution of inflammation [41].…”

Section: Evs and Liver Inflammationmentioning

confidence: 99%

Extracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy

Hernández

Arab

Reyes

et al. 2020

Cells

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In recent years, knowledge on the biology and pathobiology of extracellular vesicles (EVs) has exploded. EVs are submicron membrane-bound structures secreted from different cell types containing a wide variety of bioactive molecules (e.g., proteins, lipids, and nucleic acids (coding and non-coding RNA) and mitochondrial DNA). EVs have important functions in cell-to-cell communication and are found in a wide variety of tissues and body fluids. Better delineation of EV structures and advances in the isolation and characterization of their cargo have allowed the diagnostic and therapeutic implications of these particles to be explored. In the field of liver diseases, EVs are emerging as key players in the pathogenesis of both nonalcoholic liver disease (NAFLD) and alcoholic liver disease (ALD), the most prevalent liver diseases worldwide, and their complications, including development of hepatocellular carcinoma. In these diseases, stressed/damaged hepatocytes release large quantities of EVs that contribute to the occurrence of inflammation, fibrogenesis, and angiogenesis, which are key pathobiological processes in liver disease progression. Moreover, the specific molecular signatures of released EVs in biofluids have allowed EVs to be considered as promising candidates to serve as disease biomarkers. Additionally, different experimental studies have shown that EVs may have potential for therapeutic use as a liver-specific delivery method of different agents, taking advantage of their hepatocellular uptake through interactions with specific receptors. In this review, we focused on the most recent findings concerning the role of EVs as new structures mediating autocrine and paracrine intercellular communication in both ALD and NAFLD, as well as their potential use as biomarkers of disease severity and progression. Emerging therapeutic applications of EVs in these liver diseases were also examined, along with the potential for successful transition from bench to clinic.

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Platelets and Platelet‐Derived Extracellular Vesicles in Liver Physiology and Disease

Cited by 28 publications

References 139 publications

Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies

Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies

Extracellular vesicles in metabolic disease

Extracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy

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