Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critically [corrected] ill patients?

Abstract

Beyond haemostasis, platelets have emerged as versatile effectors of the immune response. The contribution of platelets in inflammation, tissue integrity and defence against infections has considerably widened the spectrum of their role in health and disease. Here, we propose a narrative review that first describes these new platelet attributes. We then examine their relevance to microcirculatory alterations in multi-organ dysfunction, a major sepsis complication. Rapid progresses that are made on the knowledge of novel platelet functions should improve the understanding of thrombocytopenia, a common condition and a predictor of adverse outcome in sepsis, and may provide potential avenues for management and therapy.

Keywords: Inflammation; Intensive care; Platelets; Sepsis.

Figures

Fig. 1

Platelets are integral players in the immune response, linking haemostasis, thrombosis, inflammation, pathogen clearance and tissue repair: a schematic representation. A growing body of evidence highlights a role for platelets beyond the confines of haemostasis and thrombosis. Some of platelet interfaces in innate immune response are schematized. Platelets are activated at sites of infection/tissue injury. Platelets and platelet-derived mediators contribute to arrest bleeding, to clear pathogens directly or indirectly by acting on various steps of the immune response, and to drive vascular/tissue repair by providing matrix building blocks and a multiplicity of signals that remodel matrix, attracting tissue progenitor cells and reconstructing the vascular frame. In doing so, platelets provide a coherent biological response contributing to cure infection and re-establish tissue architecture and homoeostasis. Scales are arbitrary. Platelet-derived microparticles (PMPs) recapitulate several of activated platelet functions. ECM extracellular matrix, MN monocytes, PMN polymorphonuclear neutrophils, MΦ macrophages

Fig. 2

Platelets monitor and are activated in response to noxious signals. Platelets sense and are activated by multiple signals generated in danger situations met by the organism. Interaction with pathogens, endothelial cell/tissue injury and interaction with foreign material activate platelets (see text for details). Platelet activation sparks off a broad range of responses, including the activation of various inflammation and coagulation pathways. Signals generated in inflammation and coagulation can in return activate platelets (thin arrow). PMPs platelet microparticles

Fig. 3

Microvasculature is a critical target of platelet activation in sepsis. Platelets circulate more concentrated close to the vascular wall and sense endothelium disturbances. In sepsis, many cellular and soluble actors concur to activate the endothelium. Activated/injured endothelium is a key driver of platelet activation. Signals generated by infection, inflammation and coagulation can also activate platelets in sepsis. The relative importance of platelet activation by PAMPs in sepsis is not well established. Platelet activation contributes to fuel various pro-inflammatory and pro-coagulant pathways with potential deleterious consequences on endothelium homoeostasis and integrity. Unmitigated platelet activation in sepsis may take a significant part in the complex global scenario that leads to impairment of the endothelium barrier and microcirculatory failure, a leading cause of organ dysfunction in sepsis. Only some pathophysiological events are schematized (see text for details). Scales are arbitrary. ROS reactive oxygen species, EC endothelial cells, NET neutrophils extracellular traps, PMPs platelet microparticles, ECM extracellular matrix