Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis

Hally, Kathryn; Fauteux‐Daniel, Sébastien; Hamzeh‐Cognasse, Hind; Larsen, Peter; Cognasse, Fabrice

doi:10.3390/ijms21176150

Cited by 66 publications

(69 citation statements)

References 182 publications

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“…1 However, platelets can also be actively involved in the inflammatory response by interacting with endothelial cells and circulating leukocytes. 2,3 Either through direct interactions or the release of soluble mediators, platelets can influence both innate (neutrophils, monocytes, and macrophages) and adaptive immune cells (lymphocytes). Platelets communicate with the immune system to recruit and initiate an inflammatory response [4][5][6] and, also by virtue of their number in circulation, can therefore be considered the primary sentinels of the bloodstream.…”

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confidence: 99%

“…Platelets communicate with the immune system to recruit and initiate an inflammatory response [4][5][6] and, also by virtue of their number in circulation, can therefore be considered the primary sentinels of the bloodstream. 2 Aside from initiation, platelets also have a recently appreciated role in resolving inflammation. Platelets contribute to this resolution in several ways, including interaction and modification of immune (T cells, neutrophils, and macrophages) and nonimmune cells (endothelial cells).…”

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confidence: 99%

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Effects and Side Effects of Platelet Transfusion

et al. 2021

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Aside from their canonical role in hemostasis, it is increasingly recognized that platelets have inflammatory functions and can regulate both adaptive and innate immune responses. The main topic this review aims to cover is the proinflammatory effects and side effects of platelet transfusion. Platelets prepared for transfusion are subject to stress injury upon collection, preparation, and storage. With these types of stress, they undergo morphologic, metabolic, and functional modulations which are likely to induce platelet activation and the release of biological response modifiers (BRMs). As a consequence, platelet concentrates (PCs) accumulate BRMs during processing and storage, and these BRMs are ultimately transfused alongside platelets. It has been shown that BRMs present in PCs can induce immune responses and posttransfusion reactions in the transfusion recipient. Several recent reports within the transfusion literature have investigated the concept of platelets as immune cells. Nevertheless, current and future investigations will face the challenge of encompassing the immunological role of platelets in the scope of transfusion.

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Effects and Side Effects of Platelet Transfusion

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“…DVT and pulmonary embolism occurred in a lady being treated for idiopathic thrombocytopenia purpura with intravenous immunoglobulin (Lee et al, 2007). (Hally et al, 2020) provide an overview of the platelet TOLL-like receptors including their response to PAMPS and DAMPS. They note that fibroblast stimulating lipopeptide-1 (FSL-1) is found to stimulate platelet production of IL-6 via the TLR2/6 receptors.…”

Section: Resultsmentioning

confidence: 99%

“…They suggest that a COVID-19-related generalised thrombotic microvascular injury results from complement activation. Numerous cases of collapsing glomerulopathy have been described in COVID-19 (Larsen et al, 2020)(Gaillard et al, 2020)(Peleg et al, 2020)(Nasr et al, 2020)(Magoon et al, 2020)(Jhaveri et al, 2020)(Kadosh et al, 2020). Collapsing glomerulopathy as a morphological variant of focal segmental glomerulosclerosis is in turn associated both with thrombotic microangiopathy (Buob et al, 2016) and alternative complement pathway activation (Thurman et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

Characterising COVID-19 as a Viral Clotting Fever: A Mixed Methods Scoping Review

Marley

2020

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BackgroundThe COVID-19 pandemic has claimed over 1 million lives globally and results from the SARS-COV2 virus. COVID-19 is associated with a coagulopathy. In this mixed-methods PRISMA-compliant scoping review, we set out to determine if ARDS, sepsis and DIC could account for the coagulopathy and if there were any other features of the coagulopathy we could determine so as to inform future research. Methods: We used a search strategy to identify papers with clinically relevant thromboembolic events in COVID-19. We then developed a technique referred to as an Abridged Thematic Analysis (ATA) to quickly identify themes in the papers so as to increase the yield of clinically relevant information. We further developed Validated Abridged Thematic Analysis (VATA) to validate the resulting taxonomy of themes. Finally we developed a number of methods that can be used by other researchers to take forwards this work. Results: We identified 56 studies with 10,523 patients, 456 patients with COVID-19 and thromboembolic events (TBE’s) and 586 thrombembolic events. There were an average of 1.3 TBE’s per patient. There were five main arterial territories with corresponding clinical sequelae: Acute limb ischaemia, myocardial infarcts, strokes, mesenteric ischaemia and pulmonary embolism. We also identified DVT’s. There were two further groups: medical-device-related coagulopathy and dermal lesions. In a subgroup of 119 patients we found mortality ranged from 26% in DVT to 79% in acute limb ischaemia although there was evidence of selection bias in the latter group. All patients were hospitalised and the average age of survivors was 63 versus 73 for those who died. 91/150 patients with TE’s had fever. From the ATA, we identified 16 characteristics of the clotting pathology in COVID-19. From the VATA, we identified 34 mechanisms leading to coagulopathy and grouped them according to Virchow’s triad of vascular damage, stasis and hypercoagulability. Coagulopathy occurred with and without each of ARDS, Sepsis and DIC. We conclude that COVID-19 leads to the syndrome of a viral clotting fever in a subgroup of patients and that the presentation of coagulopathy and fever should raise the possibility of COVID-19 as a differential. We make recommendations for future research studies.

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“…• Upregulation of expression of platelet activation markers, i.e., CD62P and CD40L (127,130,134,135 bind to TLRs resulting in activation of platelets (198). This sustained platelet activation may contribute to the persistent inflammation and cardiovascular morbidities observed in HIV-infected individuals, despite cART (130).…”

Section: Platelet Activation Increasedmentioning

confidence: 99%

Interactions of HIV and Antiretroviral Therapy With Neutrophils and Platelets

et al. 2021

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Neutrophils are important components of the innate immune system that mediate pathogen defense by multiple processes including phagocytosis, release of proteolytic enzymes, production of reactive oxygen species, and neutrophil extracellular trap formation. Abnormalities of neutrophil count and function have been described in the setting of HIV infection, with the majority of antiretroviral agents (ARVs), excluding zidovudine, having been reported to correct neutropenia. Questions still remain, however, about their impact on neutrophil function, particularly the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment. In this context, the effects of protease inhibitors and integrase strand transfer inhibitors, in particular, on neutrophil function remain poorly understood and deserve further study. Besides mediating hemostatic functions, platelets are increasingly recognized as critical role players in the immune response against infection. In the setting of HIV, these cells have been found to harbor the virus, even in the presence of antiretroviral therapy (ART) potentially promoting viral dissemination. While HIV-infected individuals often present with thrombocytopenia, they have also been reported to have increased platelet activation, as measured by an upregulation of expression of CD62P (P-selectin), CD40 ligand, glycoprotein IV, and RANTES. Despite ART-mediated viral suppression, HIV-infected individuals reportedly have sustained platelet activation and dysfunction. This, in turn, contributes to persistent immune activation and an inflammatory vascular environment, seemingly involving neutrophil-platelet-endothelium interactions that increase the risk for development of comorbidities such as cardiovascular disease (CVD) that has become the leading cause of morbidity and mortality in HIV-infected individuals on treatment, clearly underscoring the importance of unraveling the possible etiologic roles of ARVs. In this context, abacavir and ritonavir-boosted lopinavir and darunavir have all been linked to an increased risk of CVD. This narrative review is therefore focused primarily on the role of neutrophils and platelets in HIV transmission and disease, as well as on the effect of HIV and the most common ARVs on the numbers and functions of these cells, including neutrophil-platelet-endothelial interactions.

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Revisiting Platelets and Toll-Like Receptors (TLRs): At the Interface of Vascular Immunity and Thrombosis

Cited by 66 publications

References 182 publications

Effects and Side Effects of Platelet Transfusion

Effects and Side Effects of Platelet Transfusion

Characterising COVID-19 as a Viral Clotting Fever: A Mixed Methods Scoping Review

Interactions of HIV and Antiretroviral Therapy With Neutrophils and Platelets

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