Abstract Number: VPB0607
Meeting: ISTH 2022 Congress
Background: Nitric oxide (NO) regulates both thrombosis and vascular leakage, two of the major complications of severe Covid19. Platelet-derived NO inhibits adhesion/aggregation and within microvascular endothelial cells NO-signalling mediates vascular endothelial growth factor (VEGF/VPF)-induced permeability. Recently, we identified novel platelet subpopulations with a differential ability to produce NO and the presence/absence of endothelial nitric oxide synthase (eNOS). We showed that eNOS-negative (eNOSneg) platelets initiate adhesion and aggregation, while eNOS-positive (eNOSpos) platelets limit aggregate growth. As inflammatory cytokines are known to counter-regulate eNOS and VEGF expression, we hypothesized that the ratio of eNOS-negative to –positive platelets may be increased in COVID-19 patients along with their VEGF content.
Aims: To determine the eNOS-positive to –negative platelet ratio and platelet VEGF levels within the blood of hospitalized COVID-19 patients.
Methods: Platelets were isolated from age- and sex-matched COVID-19 patients (ICU and non-ICU) and COVID-negative controls. Platelets were immunostained for eNOS, VEGF, and surface CD62P then analyzed using flow cytometry. A multiplex assay was used to measure plasma cytokines.
Results: The percentage of eNOSneg platelets within the blood of COVID-19 patients (ICU and non-ICU) was higher than that within healthy controls and their levels correlated with disease severity (81.2±2.8% ICU vs. 66.0 ±3.1% non-ICU vs. 6.1±1.3% controls, P-value < 0.001; Fig. 1). Accordingly, the percentage of eNOSpos platelets in COVID-19 patients was lower compared to controls, while the platelet VEGF content and surface CD62P of COVID-19 patients in ICU was higher than that of healthy controls (Fig. 2). Further, COVID-19 patients demonstrated higher TNFα, IL-6, and IL-1β plasma concentrations than controls.
Conclusion(s): Preliminary data suggests that eNOS-negative to -positive platelet ratios and VEGF content increase with COVID-19 severity, potentially predisposing patients to thrombosis and enhanced vascular permeability upon platelet activation. These platelet changes may be due to the actions of inflammatory cytokines on megakaryocytes.
To cite this abstract in AMA style:Asgari A, Ritchie B, Jurasz P. A Comparison of eNOS-based Platelet Subpopulation Ratios and Platelet VEGF Content within COVID-19 [abstract]. https://abstracts.isth.org/abstract/a-comparison-of-enos-based-platelet-subpopulation-ratios-and-platelet-vegf-content-within-covid-19/. Accessed November 30, 2023.
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