The role of platelets in sepsis

Abstract

Platelets are small circulating anucleate cells that are of crucial importance in haemostasis. Over the last decade, it has become increasingly clear that platelets play an important role in inflammation and can influence both innate and adaptive immunity. Sepsis is a potentially lethal condition caused by detrimental host response to an invading pathogen. Dysbalanced immune response and activation of the coagulation system during sepsis are fundamental events leading to sepsis complications and organ failure. Platelets, being major effector cells in both haemostasis and inflammation, are involved in sepsis pathogenesis and contribute to sepsis complications. Platelets catalyse the development of hyperinflammation, disseminated intravascular coagulation and microthrombosis, and subsequently contribute to multiple organ failure. Inappropriate accumulation and activity of platelets are key events in the development of sepsis-related complications such as acute lung injury and acute kidney injury. Platelet activation readouts could serve as biomarkers for early sepsis recognition; inhibition of platelets in septic patients seems like an important target for immune-modulating therapy and appears promising based on animal models and retrospective human studies.

Contribution of Human Thrombospondin-1 to the Pathogenesis of Gram-Positive Bacteria

“…Due to their high number in the circulatory system and the expression of immune receptors, platelets can be considered as the first responding innate immune cells towards invading bacteria. Platelet activation is a common observation in septic patients, and it has therefore been suggested as biomarker for the development of sepsis [88]. …”

Can we find accessible and relevant markers for sepsis outcome?

“…(36,37) In septic patients thrombocytopenia is due to platelet consumption because of exacerbated activation of the coagulation system, also leading to coagulation factor consumption. Boechat et al proved that a platelet count lower than 150x10³/ uL was significantly correlated with mortality in patients with sepsis and that normalization of platelet count improved prognosis.…”

Platelets in sepsis — are there any new aspects?

“…PF4 binds to bacteria and reduces the lag time for aggregation. Other platelet receptors that mediate platelet-bacterial interactions are GPIbα, PAR1, and TLRs [8]. It has been suggested that platelets, through the expression of TLR4, act as a barometer for systemic infection [17] and function as sensors of pathogens.…”

“…During sepsis, an increase in circulating platelet-neutrophil complexes is observed. These complexes initially rise in the beginning of sepsis and decrease when MODS (multiple organ dysfunction syndrome) occurs indicating peripheral sequestration [8].…”

“…Activated platelets enhance further platelet activation via catalysation of the coagulation cascade, TXA2 and ADP release [8].…”