Alterations in platelet proteome signature and impaired platelet integrin αIIbβ3 activation in patients with COVID-19

J Thromb Haemost. 2023 May;21(5):1307-1321. doi: 10.1016/j.jtha.2023.01.018. Epub 2023 Jan 28.

Abstract

Background: Patients with COVID-19 are at increased risk of thrombosis, which is associated with altered platelet function and coagulopathy, contributing to excess mortality.

Objectives: To characterize 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 hospitalized with COVID-19 and healthy control subjects using tandem mass tag proteomic analysis, Western blotting, and flow cytometry.

Results: COVID-19 patients showed a different profile of platelet protein expression (858 altered of the 5773 quantified). Levels of COVID-19 plasma markers were enhanced in the platelets of COVID-19 patients. Gene ontology pathway analysis demonstrated that the levels of granule secretory proteins were raised, whereas those of platelet activation proteins, such as the thrombopoietin receptor and protein kinase Cα, were lowered. Basally, platelets of COVID-19 patients showed enhanced phosphatidylserine exposure, with unaltered integrin αIIbβ3 activation and P-selectin expression. Agonist-stimulated integrin αIIbβ3 activation and phosphatidylserine exposure, but not P-selectin expression, were decreased in COVID-19 patients. COVID-19 patients had high levels of platelet-neutrophil aggregates, even under basal conditions, compared to controls. This association was disrupted by blocking P-selectin, demonstrating that platelet P-selectin is critical for the interaction.

Conclusions: Overall, our data suggest the presence of 2 platelet populations in patients with COVID-19: one of circulating platelets with an altered proteome and reduced functional responses and another of 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets / metabolism
  • COVID-19* / complications
  • Humans
  • Inflammation / metabolism
  • Phosphatidylserines / metabolism
  • Platelet Activation
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Proteome / metabolism
  • Proteomics
  • Selectins / metabolism
  • Thrombosis* / etiology

Substances

  • Proteome
  • Phosphatidylserines
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Selectins