PB0085 - Impaired exercise capacity in Post-COVID syndrome: The role of VWF-ADAMTS13 axis

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Nithya Prasannan

Consultant Haematologist
University College Hospitals London NHS Foundation Trust
London, England, United Kingdom

Co-Author(s)

MH

Melissa Heightman

Respiratory Consultant
UCLH
London, England, United Kingdom
TH

Toby Hillman

Respiratory Consultant
UCLH
London, England, United Kingdom
EW

Emma Wall

Consultant
UCLH
London, England, United Kingdom
RB

Robert Bell

Cardiology Consultant
UCLH
London, England, United Kingdom
AK

Anna Kessler

Clinical Fellow
UCLH
London, England, United Kingdom
Lucy Neave, MBBS MRCP FRCPath

Clinical Research Fellow
UCLH Hospitals NHS Trust / Haemostasis Research Unit, University College London
London, England, United Kingdom
Andrew J. Doyle, MBChB MRCP FRCPath

Consultant Haematologist
Guy's & St Thomas' NHS Foundation Trust
London, England, United Kingdom
AD

Akshitha Devaraj

Clinical Fellow
UCLH
London, England, United Kingdom
DS

Deepak Singh

Head of Special Coagulation
Health Services Laboratories
London, England, United Kingdom
HD

Hakim-Moulay Dehbi

Statistician
UCL
London, England, United Kingdom
MS

Marie Scully

Professor
Bloomsbury Institute of Intensive Care Medicine
London, England, United Kingdom

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.