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J Thromb Haemost
. 2023 Jan 27;S1538-7836(23)00059-4.
doi: 10.1016/j.jtha.2023.01.018. Online ahead of print.
Alterations in platelet proteome signature and impaired platelet integrin αIIbβ3 activation in patients with COVID-19
Lucy J Goudswaard 1 , Christopher M Williams 2 , Jawad Khalil 2 , Kate L Burley 2 , Fergus Hamilton 3 , David Arnold 4 , Alice Milne 4 , Phil A Lewis 5 , Kate J Heesom 5 , Stuart J Mundell 2 , Andrew D Davidson 6 , Alastair W Poole 2 , Ingeborg Hers 7
Affiliations
- PMID: 36716966
- PMCID: PMC9883069
- DOI: 10.1016/j.jtha.2023.01.018
Abstract
Background: Patients with coronavirus disease-19 (COVID-19) are at increased risk of thrombosis, which is associated with altered platelet function and coagulopathy, contributing to excess mortality.
Objectives: We aimed to characterise the mechanism of altered platelet function in COVID-19 patients.
Methods: The platelet proteome, platelet functional responses and platelet-neutrophil aggregates were compared between patients hospitalised with COVID-19 and healthy control subjects using Tandem Mass Tag (TMT) proteomic analysis, Western blotting and flow cytometry.
Results: COVID-19 patients showed a different profile of platelet protein expression (858 altered out of 5773 quantified). Levels of COVID-19 plasma markers were enhanced in COVID-19 platelets. Gene ontology (GO) pathway analysis demonstrated that levels of granule secretory proteins were raised, whereas some platelet activation proteins, such as the thrombopoietin receptor and PKCα, were lowered. Basally, COVID-19 platelets showed enhanced phosphatidylserine (PS) exposure, with unaltered integrin αIIbβ3 activation and P-selectin expression. Agonist-stimulated integrin αIIbβ3 activation and PS exposure, but not P-selectin expression, were significantly decreased in COVID-19 patients. COVID-19 patients had high levels of platelet-neutrophil aggregates, even under basal conditions, compared to controls. This interaction was disrupted by blocking P-selectin, demonstrating that platelet P-selectin is critical for the interaction.
Conclusions: Overall, our data suggests the presence of two platelet populations in patients with COVID-19: one with circulating platelets with an altered proteome and reduced functional responses and another with P-selectin expressing neutrophil-associated platelets. Platelet driven thromboinflammation may therefore be one of the key factors enhancing the risk of thrombosis in COVID-19 patients.
Keywords: COVID-19; SARS-CoV-2; platelet activation; proteomics; thromboinflammation.