1. Sign our petition calling on Cochrane to withdraw their review of Exercise Therapy for CFS here.
    Dismiss Notice
  2. Guest, the 'News in Brief' for the week beginning 18th March 2024 is here.
    Dismiss Notice
  3. Welcome! To read the Core Purpose and Values of our forum, click here.
    Dismiss Notice

Impaired exercise capacity in post-COVID syndrome: the role of VWF-ADAMTS13 axis, 2022, Prasannan et al

Discussion in 'Long Covid research' started by LarsSG, May 11, 2022.

  1. LarsSG

    LarsSG Senior Member (Voting Rights)

    Messages:
    370
    Key Points
    • VWF(Ag):ADAMTS13 ratio ≥1.5 was evident in 28% of PCS cohort
    • 55% of patients with impaired exercise capacity had a raised VWF(Ag):ADAMTS13 ratio ≥1.5 (OR 4)
    Post-COVID syndrome (PCS) or Long-COVID 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, quantified by elevated Von Willebrand Factor (VWF) Antigen (Ag):ADAMTS13 ratio, and is associated with severity of acute COVID-19 infection. We 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.

    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. These 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.

    Link with full text PDF
     
    Mij, Grigor, DokaGirl and 7 others like this.
  2. Hutan

    Hutan Moderator Staff Member

    Messages:
    26,534
    Location:
    Aotearoa New Zealand
    ADAMTS13 regulates VWF. In acute Covid, an increase in VWF:Ag(antigen) and a decrease in ADAMTS13 has been reported.
    50 healthy controls were used to determine the healthy VWF(Ag)/ADAMTS13 ratio. They don't say whether some/all the healthy controls had recovered from Covid-19, or the age or sex ratio of the controls.
    72% of the patients reported fatigue - overall this was a mixed patient group reporting a range of symptoms including chest discomfort. 3% of the patient group are reported as being asymptomatic.


    So, median VWF(Ag)/ADAMTS13 ratio in controls was 0.98 (interquartile range 0.76 to 1.34). The ratio in patients was 1.2 (0.9-1.5). I think it is a bit of a stretch to say these are different if we take into account confounding factors like age.
    Execise test:
    I don't think the exercise test measure is a very sensitive test of exercise capacity in ME/CFS. Below, the chart comparing the ratios of those patients with normal and abnormal exercise test performance. The y axis is 0,1,2,3,4. Perhaps there is something there, bearing in mind the median of the healthy controls was approximately 1. I think we'd need to see the analysis repeated with just people reporting fatigue to begin to get an idea as to whether this is relevant to people with ME/CFS-like symptoms.

    Screen Shot 2023-07-11 at 5.20.14 am.png

    The chart is only for the subset who completed the test - not all patients did the exercise test, and some attempting it did not complete it.
    It's of note that older people had higher ratios - perhaps this accounts for the difference with the controls?
     
    Last edited: Jul 10, 2023
    SNT Gatchaman likes this.
  3. Hutan

    Hutan Moderator Staff Member

    Messages:
    26,534
    Location:
    Aotearoa New Zealand
    I had thought that the older people might have been more likely to have severe disease, and so the higher ratio might just have been a result of lung or heart damage, or of their treatments. It doesn't look as though hospitalisation/severe acute disease alone accounts for higher ratios here.

    But it looks as though a previous study did find a relationship between severe acute disease and the ratio; perhaps that is mediated by age?

    It's not clear to me what the basis of the authors saying that the ratio was not correlated with fatigue presence. The report is a bit patchy.

    I'm not finding the VWF(Ag): ADAMSTS13 ratio very compelling as a reason for ME/CFS-like symptoms.
     
    Last edited: Jul 10, 2023
    SNT Gatchaman likes this.

Share This Page