Sepsis - it is all about the platelets

Dermot Cox, Dermot Cox

Abstract

Sepsis is accompanied by thrombocytopenia and the severity of the thrombocytopenia is associated with mortality. This thrombocytopenia is characteristic of disseminated intravascular coagulation (DIC), the sepsis-associated coagulopathy. Many of the pathogens, both bacterial and viral, that cause sepsis also directly activate platelets, which suggests that pathogen-induced platelet activation leads to systemic thrombosis and drives the multi-organ failure of DIC. In this paper we review the mechanisms of platelet activation by pathogens and the evidence for a role for anti-platelet agents in the management of sepsis.

Keywords: anti-platelet agents; innate immunity; platelets; sepsis; thrombosis.

Conflict of interest statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2023 Cox.

Figures

Figure 1
Figure 1
Showing the main mechanisms of pathogen-induced platelet activation. (A) Bacteria such as S. aureus express proteins that bind fibrinogen which in turn binds to GPIIb/IIIa. Simultaneously, IgG binds to the bacteria and also to FcγRIIa generating an activation signal. (B) Any bacteria can bind IgG which in turn leads to the assembly of complement. The IgG binds to FcγRIIa and the complement to a complement receptor to generate an activation signal. (C) Bacteria such as H. pylori express a protein that binds vWF, which in turn binds GPIb. IgG also binds to the bacteria and also to FcγRIIa generating an activation signal. (D) Bacteria such as S. sanguinis express proteins (e.g. serine-repeat protein; srp) that can directly bind GPIb. This generates an FcγRIIa-dependent activation signal. (E) Bacteria such as S. pneumonia express a protein that binds to Toll-like receptor (TLR) 2. In conjunction with IgG engagement of FcγRIIa they can generate an activation signal. (F) DENV E-glycoprotein can bind directly to DC-SIGN and non-structural protein (NSP)-1 can bind to TLR4. In conjunction with IgG binding to FcγRIIa this leads to the generation of an activation signal. (G) Some viruses express proteins that bind to TLR (e.g TLR 2, 4 &7) leading to a platelet activation signal.

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Source: PubMed

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