tetano
Editor, Senior Moderator
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 α[SUB]IIb[/SUB]β[SUB]3[/SUB] activation in patients with COVID-19
Lucy J Goudswaard[SUP] 1 [/SUP], Christopher M Williams[SUP] 2 [/SUP], Jawad Khalil[SUP] 2 [/SUP], Kate L Burley[SUP] 2 [/SUP], Fergus Hamilton[SUP] 3 [/SUP], David Arnold[SUP] 4 [/SUP], Alice Milne[SUP] 4 [/SUP], Phil A Lewis[SUP] 5 [/SUP], Kate J Heesom[SUP] 5 [/SUP], Stuart J Mundell[SUP] 2 [/SUP], Andrew D Davidson[SUP] 6 [/SUP], Alastair W Poole[SUP] 2 [/SUP], Ingeborg Hers[SUP] 7 [/SUP]
Affiliations
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 α[SUB]IIb[/SUB]β[SUB]3[/SUB] activation and P-selectin expression. Agonist-stimulated integrin α[SUB]IIb[/SUB]β[SUB]3[/SUB] 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.
. 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 α[SUB]IIb[/SUB]β[SUB]3[/SUB] activation in patients with COVID-19
Lucy J Goudswaard[SUP] 1 [/SUP], Christopher M Williams[SUP] 2 [/SUP], Jawad Khalil[SUP] 2 [/SUP], Kate L Burley[SUP] 2 [/SUP], Fergus Hamilton[SUP] 3 [/SUP], David Arnold[SUP] 4 [/SUP], Alice Milne[SUP] 4 [/SUP], Phil A Lewis[SUP] 5 [/SUP], Kate J Heesom[SUP] 5 [/SUP], Stuart J Mundell[SUP] 2 [/SUP], Andrew D Davidson[SUP] 6 [/SUP], Alastair W Poole[SUP] 2 [/SUP], Ingeborg Hers[SUP] 7 [/SUP]
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 α[SUB]IIb[/SUB]β[SUB]3[/SUB] activation and P-selectin expression. Agonist-stimulated integrin α[SUB]IIb[/SUB]β[SUB]3[/SUB] 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.