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Impaired exercise capacity in Post-COVID syndrome: The role of VWF-ADAMTS13 axis

N. Prasannan1, M. Heightman2, T. Hillman2, E. Wall2, R. Bell2, A. Kessler2, L. Neave3, A. Doyle4, A. Devaraj2, D. Singh5, H. Dehbi6, M. Scully1

1University College Hospitals London NHS Foundation Trust, London, England, United Kingdom, 2UCLH, London, England, United Kingdom, 3UCLH Hospitals NHS Trust / Haemostasis Research Unit, University College London, London, England, United Kingdom, 4Guy's & St Thomas' NHS Foundation Trust, London, England, United Kingdom, 5Health Services Laboratories, London, England, United Kingdom, 6UCL, London, England, United Kingdom

Abstract Number: PB0085

Meeting: ISTH 2022 Congress

Theme: COVID and Coagulation » COVID and Coagulation, Clinical

Background: Post-COVID syndrome (PCS) is an increasingly recognised complication of acute SARS-CoV-2 infection, characterised by persistent fatigue, reduced exercise tolerance, chest pain, shortness of breath and cognitive slowing. Acute COVID-19 is strongly linked with increased risk of thrombosis; a prothrombotic state. Elevated Von Willebrand Factor (VWF) Antigen (Ag):ADAMTS13 ratio is associated with severity of acute COVID-19 infection.

Aims: We hypothesised that the pro-thrombotic state is implicated in the pathogenesis of PCS.

We investigated specialist coagulation parameters associated with reduced exercise capacity in patients with PCS to identify the utility of these parameters to determine ongoing disease activity. We also investigated if an association exists between elevated VWF(Ag):ADAMTS13 ratio and impaired exercise capacity in patients with PCS.

Methods: Retrospective analysis of VWF(Ag):ADAMTS13 ratio in patients with PCS at a dedicated post-COVID clinic. VWF(Ag):ADAMTS13 ratio was correlated with symptoms including exercise capacity as assessed by 1 minute sit-to-stand (STS) test and/or 6 minute walk test (6MWT). Peripheral oxygen desaturation ≥3% for 6MWT and STS test, and increase in lactate>1 from baseline during 6MWT were taken as markers of impaired exercise capacity.

Results: Elevated VWF(Ag):ADAMTS13 ratio (≥1.5) was found to be four times (OR 4.3) more likely in patients with impaired exercise capacity. 20% (56/276) had impaired exercise capacity, of which 55% (31/56) had a raised VWF(Ag):ADAMTS13 ratio ≥1.5 (p < 0.0001). A higher median VWF(Ag):ADAMTS13 ratio of 1.5 (IQR 1.2-1.7) in patients with abnormal exercise testing compared to 1.1 (IQR 0.9-1.4) in patients with normal exercise testing was found (p < 0.0001). FVIII and VWF(Ag) were elevated in 26% and 18% respectively and support a hypercoagulable state in patients with PCS.

Conclusion(s): These findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and highlight the potential role for prophylactic anticoagulation in the management of these patients.

Table

Proportion of patients with normal and raised VWF-Ag-:ADAMTS13 ratios split according to exercise test result. Significantly more patients with an abnormal exercise test had a VWF-Ag-:ADAMTS13 ratio≥1.5 -p < 0.0001, OR 4.3-

Image

Median VWF-Ag-:ADAMTS13 ratio in patients with normal and abnormal exercise tests. Median VWF-Ag-:ADAMTS13 ratio was 1.5 in patients with an abnormal exercise test compared to median ratio of 1.1 in patients with a normal exercise test -p < 0.0001-.

To cite this abstract in AMA style:

Prasannan N, Heightman M, Hillman T, Wall E, Bell R, Kessler A, Neave L, Doyle A, Devaraj A, Singh D, Dehbi H, Scully M. Impaired exercise capacity in Post-COVID syndrome: The role of VWF-ADAMTS13 axis [abstract]. https://abstracts.isth.org/abstract/impaired-exercise-capacity-in-post-covid-syndrome-the-role-of-vwf-adamts13-axis/. Accessed September 21, 2023.

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