Platelets in infectious disease

Middleton, Elizabeth; Rondina, Matthew T.

doi:10.1182/asheducation-2016.1.256

Cited by 20 publications

(19 citation statements)

References 55 publications

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“…Conversely, our multivariate analysis showed that, as the PDW values increased, the probability of death decreased. Thus, our data suggest the role of platelets as host defense effectors in agreement with these studies [38][39][40][41][42] .…”

Section: Discussionsupporting

confidence: 91%

Immunologic Biomarkers, Morbidity and Mortality Among HIV Patients Hospitalized in a Tertiary Care Hospital in the Brazilian Amazon

Mota

Almeida

Santos

et al. 2020

Preprint

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Background: While antiretroviral therapy (ART) has significantly improved survival rates of people living with HIV, some regions in Brazil still show a linear trend of growth in the opportunistic infections that cause HIV-associated mortality. We aimed to describe HIV-associated morbidity and mortality among hospitalized medical patients in a tertiary care hospital in Manaus, in the Brazilian Amazon, by investigating clinical data and immunologic biomarkers in order to assess predictive factors of mortality in this patient group. Methods: We prospectively measured concentrations of cytokines Th1/Th2/Th17 and soluble CD14 (sCD14) and reviewed the laboratory parameters and opportunistic infections in outcomes of either death or discharge of eighty-three HIV/AIDS patients who were admitted in 2017-2018 to the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) in Manaus. Results: The mortality in the sample studied was 20.5%. Tuberculosis (TB) showed a relative risk (RR) =1.86 (confidence interval (CI) 1.14 to 2.81: and p = 0.026), and weight loss was the symptom (RR=1.81; CI: 1.21 to 2.53 and p = 0.007) most highly associated with the death outcome in HIV/AIDS inpatients. Univariable analyses showed that the eosinophil count, platelet distribution width (PDW), and alanine aminotransferase were the only laboratory parameters that differed among patients who died. In relation to cytokines and sCD14 levels, no differences were found between those who died or were discharged. A multivariable logistic regression model was used to predict mortality and showed that individuals with no digestive syndrome (especially the absence of oropharyngeal candidiasis), nor TB are 63% to 76% less likely to die, respectively. In addition, increases in PDW values also decreased the probability of death. Curiously, patients who were discharged showed a trend towards a concomitant increase in PDW and mean platelet volume (MPV) in relation to those who died.Conclusions: Opportunistic infections continue to be major events in morbidity and mortality of HIV/AIDS patients, and the relationship between increased PDW and the likelihood of survival suggests the need for future studies on innate immune response of platelets in HIV/AIDS inpatients.

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Section: Discussionsupporting

confidence: 91%

Immunologic Biomarkers, Morbidity and Mortality Among HIV Patients Hospitalized in a Tertiary Care Hospital in the Brazilian Amazon

Mota

Almeida

Santos

et al. 2020

Preprint

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“…The aforementioned role of platelets in the defence against pathogens suggests that they can interfere with the progression of infection. How can these observations be translated to sepsis pathophysiology [ 120 , 124 , 126 ]? Models suggest a protective role of platelets, as, for example, in streptococcal endocarditis, malaria or gram-negative pneumonia [ 127 – 129 ], and thrombocytopenia could be a risk factor for bacterial or fungal infection.…”

Section: Platelets Contribute To the Innate Immune Response Against Imentioning

confidence: 99%

Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critical ill patients?

Dewitte

Lepreux

Villeneuve

et al. 2017

Ann. Intensive Care

124

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Beyond haemostasis, platelets have emerged as versatile effectors of the immune response. The contribution of platelets in inflammation, tissue integrity and defence against infections has considerably widened the spectrum of their role in health and disease. Here, we propose a narrative review that first describes these new platelet attributes. We then examine their relevance to microcirculatory alterations in multi-organ dysfunction, a major sepsis complication. Rapid progresses that are made on the knowledge of novel platelet functions should improve the understanding of thrombocytopenia, a common condition and a predictor of adverse outcome in sepsis, and may provide potential avenues for management and therapy.

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“…Platelets are anuclear haematopoietic cells that play an essential role in haemostasis and its pathological counterpart thrombosis. Platelets also play critical roles in other physiological and pathological processes including inflammation, 1 infection, 2 vascular integrity, 3 development 4 and cancer metastasis. 5 Currently, we have a rudimentary understanding of the role of platelets in many of these functions and how these processes vary during development and throughout adulthood.…”

Section: Introductionmentioning

confidence: 99%

Significant Hypo-Responsiveness to GPVI and CLEC-2 Agonists in Pre-Term and Full-Term Neonatal Platelets and following Immune Thrombocytopenia

et al. 2018

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Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether the hypo-responsiveness is related to altered levels of glycoprotein VI (GPVI) and integrin α2β1, or to defects in downstream signalling events by comparison to platelet activation by C-type lectin-like receptor 2 (CLEC-2). GPVI and CLEC-2 activate a Src- and Syk-dependent signalling pathway upstream of phospholipase C (PLC) γ2. Phosphorylation of a conserved YxxL sequence known as a (hemi) immunotyrosine-based-activation-motif (ITAM) in both receptors is critical for Syk activation. Platelets from human pre-term and full-term neonates display mildly reduced expression of GPVI and CLEC-2, as well as integrin αIIbβ3, accounted for at the transcriptional level. They are also hypo-responsive to the two ITAM receptors, as shown by measurement of integrin αIIbβ3 activation, P-selectin expression and Syk and PLCγ2 phosphorylation. Mouse platelets are also hypo-responsive to GPVI and CLEC-2 from late gestation to 2 weeks of age, as determined by measurement of integrin αIIbβ3 activation. In contrast, the response to G protein-coupled receptor agonists was only mildly reduced and in some cases not altered in neonatal platelets of both species. A reduction in response to GPVI and CLEC-2, but not protease-activated receptor 4 (PAR-4) peptide, was also observed in adult mouse platelets following immune thrombocytopenia, whereas receptor expression was not impaired. Our results demonstrate developmental differences in platelet responsiveness to GPVI and CLEC-2, and also following immune platelet depletion leading to reduced Syk activation. The rapid generation of platelets during development or following platelet depletion is achieved at the expense of signalling by ITAM-coupled receptors.

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Platelets in infectious disease

Cited by 20 publications

References 55 publications

Immunologic Biomarkers, Morbidity and Mortality Among HIV Patients Hospitalized in a Tertiary Care Hospital in the Brazilian Amazon

Immunologic Biomarkers, Morbidity and Mortality Among HIV Patients Hospitalized in a Tertiary Care Hospital in the Brazilian Amazon

Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critical ill patients?

Significant Hypo-Responsiveness to GPVI and CLEC-2 Agonists in Pre-Term and Full-Term Neonatal Platelets and following Immune Thrombocytopenia

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