Role of extracellular vesicles in the development of sepsis-induced coagulopathy

The advances of research on extracellular vesicles (EVs) are of particular interest to the clinicians as well as the researchers who are studying coagulation disorder in sepsis. Here, we intend to update the latest knowledge and currently unsolved problems that should be addressed.

Secreted membrane-enclosed vesicles including apoptotic bodies, exosomes, ectosomes, microvesicles, and microparticles are generically called EVs. Though the basic structure of these vesicles is the same, i.e., originating from the plasma membrane, their characteristics differ significantly depending on their surface structures and interior components. Numerous studies have shown elevated levels of circulating EVs that exhibit proinflammatory and procoagulant properties during sepsis. These EVs are known to play important roles in the development of coagulation disorder and organ dysfunction in sepsis. Coagulation disorder in sepsis is characterized by activated coagulation, disrupted anticoagulant systems, and imbalanced fibrinolytic systems. These processes collaborate with one another and contribute to the development of disseminated intravascular coagulation (DIC), with devastating consequences. As part of this pathogenesis, the membrane-exposed tissue factor, phosphatidylserine and bioactive substances contained within the vesicles, such as histones, nucleosomes, and high-mobility group box 1, contribute to the development of DIC. EVs not only upregulate the procoagulant systems by themselves, but they also disseminate prothrombotic activities by transferring their procoagulant properties to distant target cells. Though the basic concept behind the role of procoagulant properties, EVs in the development of sepsis-induced coagulopathy has started to be unveiled, knowledge of the actual status is far from satisfactory, mainly because of the lack of standardized assay procedures. Recent advances and current problems that remain to be resolved are introduced in this review.

The recent studies succeeded to elucidate the important roles of EVs in the progress of coagulation disorder in sepsis. However, further harmonization in terminology, methodology, and evaluation methods is required for future studies.