Constantinescu-Bercu, Adela;
Kessler, Anna;
de Groot, Rens;
Dragunaite, Bertina;
Heightman, Melissa;
Hillman, Toby;
Price, Laura C;
... Scully, Marie; + view all
(2023)
Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome.
Journal of Thrombosis and Haemostasis
, 21
(1)
pp. 94-100.
10.1016/j.jtha.2022.10.013.
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Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post COVID syndrome.pdf - Published Version Download (2MB) | Preview |
Abstract
Background: Post-COVID syndrome (PCS) affects millions of people worldwide, causing a multitude of symptoms and impairing quality of life months or even years after acute COVID-19. A prothrombotic state has been suggested; however, underlying mechanisms remain to be elucidated. / Objectives: To investigate thrombogenicity in PCS using a microfluidic assay, linking microthrombi, thrombin generation, and the von Willebrand factor (VWF):a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13 (ADAMTS13) axis. / Methods: Citrated blood was perfused through microfluidic channels coated with collagen or an antibody against the VWF A3 domain, and thrombogenicity was monitored in real time. Thrombin generation assays were performed and α(2)-antiplasmin, VWF, and ADAMTS13 activity levels were also measured. / Results: We investigated thrombogenicity in a cohort of 21 patients with PCS with a median time following symptoms onset of 23 months using a dynamic microfluidic assay. Our data show a significant increase in platelet binding on both collagen and anti-VWF A3 in patients with PCS compared with that in controls, which positively correlated with VWF antigen (Ag) levels, the VWF(Ag):ADAMTS13 ratio (on anti-VWF A3), and inversely correlated with ADAMTS13 activity (on collagen). Thrombi forming on collagen presented different geometries in patients with PCS vs controls, with significantly increased thrombi area mainly attributable to thrombi length in the patient group. Thrombi length positively correlated with VWF(Ag):ADAMTS13 ratio and thrombin generation assay results, which were increased in 55.5% of patients. α(2)-Antiplasmin levels were normal in 89.5% of patients. / Conclusion: Together, these data present a dynamic assay to investigate the prothrombotic state in PCS, which may help unravel the mechanisms involved and/or establish new therapeutic strategies for this condition.
| Type: | Article |
|---|---|
| Title: | Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jtha.2022.10.013 |
| Publisher version: | https://doi.org/10.1016/j.jtha.2022.10.013 |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | long COVID, microfluidics, post-COVID syndrome, thrombosis, von Willebrand factor |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10163666 |
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