Platelets and Platelet Extracellular Vesicles in Hemostasis and Sepsis

Abstract

Platelets, cell fragments traditionally thought of as important only for hemostasis, substantially and dynamically contribute to the immune system’s response to infection. In addition, there is increasing evidence that externally active platelet entities, including platelet granules and platelet extracellular vesicles (PEVs), play a role not only in hemostasis, but also in inflammatory actions previously ascribed to platelets themselves. Given the functions of platelets and PEVs during inflammation and infection, their role in sepsis is being investigated. Sepsis is a condition marked by the dysregulation of the body’s normal activation of the immune system in response to a pathogen. The mechanisms for controlling infection locally become detrimental to the host if they are applied systemically. Similar to cells traditionally ascribed to the immune system, including neutrophils, lymphocytes, and macrophages, platelets are instrumental in helping a host clear an infection, but are also implicated in the uncontrolled amplification of the immune response that leads to sepsis. Clearly, the function of platelets is more complicated than its simple structure and primary role in hemostasis initially suggest. This review provides an overview of platelet and platelet extracellular vesicle structure and function, highlighting the complex role platelets and PEVs play in the body in the context of infection and sepsis.

High Mean Platelet Volume Associates with In-Hospital Mortality in Severe Pneumonia Patients

“…We inferred that platelet activation played an important role in the progression of SP. Platelets are activated after exposure to platelet agonists, which are released from already activated platelets, impaired cells, or other inflammatory factors [20]. After activation, platelets take part in the immune system via various fashions, including direct interaction with pathogens, regulation of inflammatory responses by the congenital and complement immune system, and contact with leukocytes and specific immune system [20].…”

“…Larger platelet expresses more procoagulant surface proteins and intracellular thromboxane A2 (TXA2), presenting a greater prothrombotic potency. TXA2 can also activate the pulmonary vascular endothelium, known to be integral in the process of acute lung injury related to serious infection [20]. In addition, platelet size has been reported to be a predictive marker of cardiovascular events [9].…”

“…Thus, female patients' platelets showed more attraction and interaction with neutrophils, leading to a greater inflammatory response. Moreover, higher activated platelets could result in disseminated intravascular coagulation (DIC) and embolism in the microvasculature, aggravating cell death and organ failure [20]. Platelets in females express a greater number of surface receptors, leading to binding much more fibrinogens and thus having a better ability to promote thrombosis and embolism [23].…”

The Functional Heterogeneity of Neutrophil-Derived Extracellular Vesicles Reflects the Status of the Parent Cell

“…The most known non-cellular effects are linked to platelet-derived EVs. Many studies show that platelet EVs promote coagulation and thus play an important role in the maintenance of homeostasis [ 41 ]. Their pro-coagulant activity is linked to the PS exposure on the EVs that can provide a catalytic surface for assembly of the coagulation complexes [ 42 ].…”

Vibrio vulnificus Hemolysin: Biological Activity, Regulation of vvhA Expression, and Role in Pathogenesis

“…Although an earlier work showed that virulent isolates produced high titers of hemolysin, were resistant to inactivation by serum complement (68), further information is needed to uncover the mechanism of VVHmediated evasion of complement killing, which may help us to better understand the basis of the V. vulnificus infection process in human blood. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target for sepsis (69)(70)(71). The mechanism of bacterial-induced platelet activation by pore-forming toxins has been well characterized in other Gram-positive bacteria (72).…”