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.