Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome, 2022

Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome
Adela Constantinescu-Bercu, Anna Kessler, Rens de Groot, Bertina Dragunaite, Melissa Heightman, Toby Hillman, Laura C. Price, Ewan Brennan, Raphael Sivera, Karen Vanhoorelbeke, Deepak Singh, Marie Scully

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.

Link | PDF (J Thrombosis and Haemostasis)

 

Researchers partly funded via UK NIHR / STIMULATE-ICP.

Concluding —

 

The data look intelligible and quite convincing in this study.
The prothrombotic tendency looks statistically solid but there is major overlap. It is unlikely to be the direct cause of post-Covid symptoms as a whole.

 

See related: Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19 in acute Covid.

 

Is this a potential way to separate out long Covid related to "prothrombotic state" and thereby focus on those who may have something akin to ME/CFS?

 

I wonder if some PWME also experience a prothrombotic state due to the evidence for sticky blood?

Is this confined to COVID or is it a state which PBMCs will switch to from other causes?

(EDIT sry should have mentioned this reference to PBMCs is a result of reading the abstract in this post ...
"Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19"
https://www.s4me.info/threads/trans...-covid-19-2022-maher-et-al.31143/#post-453436 )

 

Flippant - I wonder if anyone's suggested an exercise program, CBT, and assessing it via questionnaires [PACE] --- after all, good enough for people with ME/CFS!

 

See also Generation of potentially inhibitory autoantibodies to ADAMTS13 in coronavirus disease (2023)