Abnormal Blood Clotting Due To Elevated Von Willebrand Factor (VWF) Antigen (Ag): ADAMTS13 Ratio In Most Post COVID Individuals Impairs Exercise Capacity
A new study by researchers from the Haemostasis Research Unit at the University College London-UK and the University College London Hospital-UK has found that most Post COVID individuals have an abnormal blood clotting condition due to an elevated Von Willebrand Factor (VWF) antigen (Ag): ADAMTS13 ratio that generally impairs exercise capacity in most of these individuals.
or Post-COVID syndrome (PCS) is an increasingly recognized complication of acute SARS-CoV-2 infection, characterized 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, quantified by elevated Von Willebrand Factor (VWF) Antigen (Ag): ADAMTS13 ratio, and is associated with severity of acute COVID-19 infection.
The study team investigated if patients with PCS also had evidence of a pro-thrombotic state associating with symptom severity. In a large cohort of patients referred to a dedicated post-COVID-19 clinic, thrombotic risk including VWF(Ag): ADAMTS13 ratio, was investigated.
The study findings showed that an elevated VWF(Ag):ADAMTS13 ratio (≥1.5) was raised in nearly one-third of the cohort and four times more likely in patients with impaired exercise capacity as evidenced by desaturation ≥3% and/or rise in lactate level more than 1 from baseline on 1-minute sit to stand test and/or 6-minute walk test (p<0.0001). 20% (56/276) had impaired exercise capacity, of which 55% (31/56) had a raised VWF(Ag): ADAMTS13 ratio ≥1.5 (p<0.0001). FVIII and VWF(Ag) were elevated in 26% and 18% respectively and support a hypercoagulable state in some patients with PCS.
The study findings suggest possible ongoing microvascular/endothelial dysfunction in the pathogenesis of PCS and highlight a potential role for antithrombotic therapy in the management of these patients.
The study findings were published in the peer reviewed journal: Blood Advances. https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2021006944/485206/Impaired-exercise-capacity-in-post-COVID-syndrome
The study findings indicated that a high percentage of individuals suffering from long COVID may face an increased risk of abnormal blood clotting.
The study team also found that this blood abnormality was four times more likely in those experiencing difficulties with basic exercise more than 12 weeks after their COVID-19 infection.
The research is the first to report an association between abnormal blood clotting tests and reduced exercise capacity in people with long COVID, offers important new insight into the potential mechanisms behind the longer-term effects of COVID-19 infection.
Post-COVID Syndrome (PCS) or Long COVID is a condition that occurs in individuals previously infected with COVID-19 and results in symptoms that persist months after the initial onset of infection.
Typical common symptoms include fatigue, chest pain, shortness of breath, and brain fog, and one study estimates that up to half of all
people who recover from infection continue to experience lingering symptoms.
As Long COVID is an emerging condition, its biological basis is still not fully understood.
This study provides insight into the underlying medical mechanisms, such as damage to cells that line blood vessels, of the disease.
Lead study author Dr Nithya Prasannan, of the Department of Haematology at the University College London Hospital told Thailand Medical News
, "By definition, this syndrome occurs when one experiences COVID-related symptoms long after the onset of infection that we can't attribute to any other cause or diagnosis. This study offers us laboratory and clinical evidence to begin to understand why some individuals experience Long COVID symptoms."
In order to conduct this study, a team led by Dr Melissa Heightman assessed individuals in an outpatient Post-COVID clinic between July 2020 and May 2021. Participants were said to have long COVID if they experienced symptoms three months after the onset of their original COVID-19 infection and if those symptoms persisted for at least two additional months in the absence of other contributing diagnoses.
The study team measured abnormal blood clotting markers by assessing the relative levels of two key proteins in the body. The team analyzed the ratio of Von Willebrand factor (VWF), a protein important in blood clotting, to ADAMTS13, a protein that cuts or splices VWF to prevent it from clogging blood vessels. If this ratio was raised, meaning that there was significantly more VWF than ADAMTS13 in the bloodstream, scientists characterized patients as being in a pro-thrombotic state, meaning that they could face a greater risk of developing blood clots.
Study participants also completed exercise tests, performing timed activities such as walking on a flat surface and/or repeatedly going from sitting to standing position from a chair while wearing oxygen monitors.
The study team measured oxygen levels and tested participants' blood before and after exercise to measure their lactate levels, which helped describe participant response to exertion.
Typically, during exercise, the body converts glucose (sugar) into energy using oxygen. However, when oxygen levels are depleted, the body starts producing lactate instead, which can be turned into energy without oxygen. In the study, patients who exhibited a significant decrease in oxygen levels (measured by a sensor on the patient's finger) while exercising and/or a rise in lactate afterward were said to demonstrate an impaired exercise capacity. Notably, patients with raised levels of blood clotting markers were also four times more likely to have an impaired exercise capacity.
The study team hopes in the future to assess patient bloodwork using different research platforms over the course of their long COVID illness to assess how their risk of thrombosis might change with the progression of their symptoms.
The study team suggest that this additional monitoring could not only help confirm possible mechanisms underlying long COVID, but also offer insight into the effects of potential treatment options for the condition.
Dr Prasannan explained, "I hope that people will view this research as a step forward in understanding what causes long COVID, which will hopefully help us guide future treatment options. I encourage people experiencing long COVID to participate in clinical trials when available because the more data we have, the better we can understand this condition."
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