Understanding platelet dysfunction in sepsis

Sepsis is defined as the systemic response to infection and is associated with a significant mortality rate. The role of platelets in sepsis remains incompletely understood (Fig. 1). Under normal conditions approximately 1 9 10 platelets are produced daily; however, during physiological stress, this may increase over 20 times [1]. Pro-inflammatory cytokines activate the coagulation system. This response, in combination with endothelial damage, leads to platelet activation [2]. In addition, bacteria may trigger platelet activation either directly by releasing endotoxins, or indirectly by binding to plasma proteins to form complexes that become ligands for platelet receptors [1]. Activated platelets enhance leukocyte recruitment and aggregation between leucocytes, platelets and the endothelium. This improves the efficacy of leukocyte phagocytosis and formation of neutrophil extracellular traps (NETs) which both act via proteolytic activity to destroy microbes in the microvasculature tissue. Sepsis may result in hypercoagulation due to fibrin deposition, and platelet activation. This leads to the formation of micro-thrombi, as a host defence mechanism against pathogens in which platelets play a crucial role. However, the formation of micro-thrombi and the subsequent recruitment of immune cells into the microvasculature may also result in the development of renal, lung and liver dysfunction and progressive failure. In extreme situations, this may progress to disseminated intravascular coagulation (DIC), with severe thrombocytopenia and coagulation system impairment [1, 2]. Platelet dysfunction during sepsis correlates with a poorer prognosis. Thus the number, morphology and function may be used as biomarkers for risk stratification of patients with sepsis.