Increased circulating platelet-derived extracellular vesicles in severe COVID-19 disease

The COVID-19 pandemic has brought to light the multifaceted nature of the disease, with coagulation disturbances emerging as significant contributors to its pathogenicity. While much attention has been given to understanding the role of coagulation factors, limited data exist on the involvement of extracellular vesicles (EVs) and residual cells (RCs) in COVID-19-related coagulopathies. In this study, researchers at Helsinki University Hospital and the University of Helsinki aimed to shed light on this aspect by assessing EVs and RCs in hospitalized COVID-19 patients.

Fifty hospitalized COVID-19 patients were categorized based on their D-dimer levels into high (>1.5 mg/L) or low (≤1.5 mg/L) groups, with 10 healthy controls included for comparison. The study utilized high sensitivity flow cytometry to assess medium-sized EVs (mEVs; 200-1000 nm) and large EVs/RCs (1000-4000 nm). These EVs were analyzed for specific markers associated with platelets, red blood cells, leukocytes, or endothelial cells. Additionally, lactadherin-binding was used to detect phosphatidyl serine EVs/RCs, indicating procoagulant activity. Small EVs (sEVs; 50-200 nm) and platelet integrin CD41a colocalization with general EV markers were assessed using single particle interferometric reflectance imaging sensor.

Patients with elevated D-dimer levels exhibited higher numbers of RCs and sEVs, irrespective of their cellular origin. Notably, platelet activation, reflected by increased levels of CD61+ and lactadherin+ mEVs and RCs, correlated with coagulation disturbances. Furthermore, patients with low D-dimer levels could be distinguished from healthy controls by examining the tetraspanin signatures of CD41a+ sEVs, suggesting the potential prognostic value of changes in circulating platelet sEV subpopulations during COVID-19 progression.

This study provides valuable insights into the role of EVs and RCs in COVID-19 coagulation disturbances. By leveraging advanced techniques, researchers have elucidated the association between EV characteristics and coagulation abnormalities, highlighting the potential of EV analysis as a tool for prognostication in COVID-19 patients. Further research in this area may lead to the development of targeted interventions to mitigate coagulation-related complications in COVID-19.

Helin T, Palviainen M, Lemponen M, Maaninka K, Siljander P, Joutsi-Korhonen L. (2024) Increased circulating platelet-derived extracellular vesicles in severe COVID-19 disease. Platelets 35(1):2313362. [article]

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