Platelets in Sepsis: An Update on Experimental Models and Clinical Data

Abstract

Beyond their important role in hemostasis, platelets play a crucial role in inflammatory diseases. This becomes apparent during sepsis, where platelet count and activation correlate with disease outcome and survival. Sepsis is caused by a dysregulated host response to infection, leading to organ dysfunction, permanent disabilities, or death. During sepsis, tissue injury results from the concomitant uncontrolled activation of the complement, coagulation, and inflammatory systems as well as platelet dysfunction. The balance between the systemic inflammatory response syndrome (SIRS) and the compensatory anti-inflammatory response (CARS) regulates sepsis outcome. Persistent thrombocytopenia is considered as an independent risk factor of mortality in sepsis, although it is still unclear whether the drop in platelet count is the cause or the consequence of sepsis severity. The role of platelets in sepsis development and progression was addressed in different experimental in vivo models, particularly in mice, that represent various aspects of human sepsis. The immunomodulatory function of platelets depends on the experimental model, time, and type of infection. Understanding the molecular mechanism of platelet regulation in inflammation could bring us one step closer to understand this important aspect of primary hemostasis which drives thrombotic as well as bleeding complications in patients with sterile and infectious inflammation. In this review, we summarize the current understanding of the contribution of platelets to sepsis severity and outcome. We highlight the differences between platelet receptors in mice and humans and discuss the potential and limitations of animal models to study platelet-related functions in sepsis.

The dual role of platelet‐innate immune cell interactions in thrombo‐inflammation

“…Platelets express a wide range of complement receptors, pattern recognition receptors, in particular toll‐like receptors and Fc receptors, providing the ability to sense and respond to endogenous and exogenous inflammatory and infectious signals and initiate an immune response . Following activation, platelets secrete a large array of antimicrobial and immunomodulatory molecules that can directly kill pathogens and/or enhance immune cell differentiation and activation.…”

The proportion of patients with thrombocytopenia in three human‐susceptible coronavirus infections: a systematic review and meta‐analysis

“…Another reason for the heterogeneity might lie in the incubation period, which means the time of the blood test could possibly represent diverse stages of the illness in individuals. The mechanism of coronavirus‐related thrombocytopenia may be partly explained by the inflammation microenvironment created by coronaviruses and the cytokine storm afterwards, impairment of platelet biogenesis in lungs, as well as sequestration of platelets in capillary‐rich organs, such as the lungs and liver 22–24 …”

Integration Analysis of m6A-SNPs and eQTLs Associated With Sepsis Reveals Platelet Degranulation and Staphylococcus aureus Infection are Mediated by m6A mRNA Methylation

“…It is well accepted that platelet degranulation is a typical biomarker of sepsis. In the development of sepsis, platelet dysfunction plays a critical role in tissue injury (Assinger et al, 2019). Early onset neonatal sepsis can be predicted by platelet/lymphocyte ratio (Arcagok and Karabulut, 2019).…”