Uncertainties about the Roles of Anticoagulation and Microclots in Post-acute Sequelae of SARS-CoV-2 Infection, 2023, Connors and Ariëns

Uncertainties about the Roles of Anticoagulation and Microclots in Post-acute Sequelae of SARS-CoV-2 Infection
Jean M. Connors; Robert A.S. Ariëns

Three years after the start of the pandemic, approaches to the prevention and treatment of acute Covid-19 have been established. However, post-acute sequelae of SARS-CoV-2 infection (PASC) is now the focus of current investigations searching for the etiology of the symptoms and diagnostic strategies and treatments, as up to 10% of those with acute Covid-19 will go on to develop PASC, a significant public health burden.

Some have suggested that ongoing microvascular thrombosis and microclots may play a role in the persistent sequelae of Covid-19 infection. Treatments are being given to address the presumed role of thrombosis in PASC and some suggest that randomized controlled trials of anticoagulants in patients with PASC should be performed. In this Forum article, we focus on findings from patients with PASC that have led to the suggestion of using anticoagulants and discuss alternative considerations.

Link | PDF (Journal of Thrombosis and Haemostasis)

 

I can't access this currently, but presume it will be a strong rebuttal. I hope it will discuss mechanisms of hypercoagulability as a downstream effect.

 

I also don’t have access to it, but I always find it is a bit strange to write about a topic your colleagues next door have and currently are doing research on, without supposedly even reaching out to them or even being aware of their work.

 

I think hypercoagulability in LC (and ME) will be a part of the story, so thought it was worth spending some CME funds to access this journal for a year. (Hopefully our university will add it back into the portfolio, after it became MIA since the Jan move to Elsevier). Anyhow, I have this paper now and it says many things that we have discussed here. I think it's worth quoting some of the points.

Introduction

 

Macrovascular Thrombosis

Ref: Cardiovascular disease and mortality sequelae of COVID-19 in the UK Biobank (2023, Heart)

Ref: Long-term cardiovascular outcomes of COVID-19 (2022, Nature Medicine)

Ref: Venous thromboembolism secondary to hospitalization for COVID-19: patient management and long-term outcomes (2023, Research and Practice in Thrombosis and Haemostasis)

 

Coagulation and endothelial abnormalities

Ref: Impaired exercise capacity in post–COVID-19 syndrome: the role of VWF-ADAMTS13 axis (2022, Blood Advances)

Ref: Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction (2022, Journal of Thrombosis and Haemostasis)

Ref: Serum Metabolic Profile in Patients With Long-Covid PASC Syndrome: Clinical Implications (2021, Frontiers in Medicine)

Ref: NETosis induction reflects COVID-19 severity and long COVID: insights from a 2-center patient cohort study in Israel (2023, Journal of Thrombosis and Haemostasis)

Ref: Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome (2022, Journal of Thrombosis and Haemostasis)

Ref: Elevated vascular transformation blood biomarkers in Long-COVID indicate angiogenesis as a key pathophysiological mechanism (2022, Molecular Medicine)

 

Microclots

Most references are in S4ME under the microclot tag.

 

Ref: Plasma from patients with pulmonary embolism show aggregates that reduce after anticoagulation (2023, Nature Communications Medicine)

Senior author is this article's second author. It sounds as if that paper is worth posting separately.

ETA: Thread now here.

 

The next section basically re-states what @Jonathan Edwards has consistently written here.

 

They conclude —

 

I know I've already mentioned my own experience with clotting and anticoagulants here on the forum, but just in case anybody new is reading this, here's my N=1 experience with ME/CFS and Enoxaparin sodium.

 

Iwasaki was also very recently asked about microclots since her team are investigating them as well

https://www.youtube.com/watch?v=q4YIW2aU8dw

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I thought her opinion would be a decent reflection of their current research as she has a better tone than some of the “Twitter scientists”. The gist of it (or my interpretation of it) is that Akiko confirms that they find microclots and platelet hyperactivation in people after Covid (both Long-Covid and non-Long-Covid) as well as some HC. It's still ongoing work, they still need more controls which they are busy looking for. They are still cautious about this as it’s very early days, especially when it comes to a new theory for a new disease. It sounds like it will still take longer than this till the end of this year for first results to reappear. Naturally she also didn’t speak too highly of the current testing which is of course all not standardised or performed in some solid laboratory setting.

For me the takeaway still is though that at least they’ve being seeing something which she currently doesn't interpret to be an artefact of the methods.

 

Letter to the editor from Kell, Pretorius et al. Response from authors Connors and Ariëns. (Both are paywalled)

As there is an open study into microclots at another centre, it's probably helpful to record some of the letter's arguments.

In the letter, Kell et al discuss in two sections: incorrect citations; coagulation and endothelial dysfunction. In the first section, they conclude with —

A few of the points made in the section on coagulation and endothelial dysfunction —

The author response includes —

 

Reminds me of the people who trash recipes by commenting that they substituted 4 ingredients, halved one, doubled another, and the recipe is not good!

I thought MDs were better than this. It's been a while since I thought that, but I used to think that.

Then again when the standard approach to generic psychosocial rehabilitation doesn't care about substance, it seems natural that they would apply the same non-thinking to biomedical treatments, since the problem isn't with the treatments themselves but rather the patients, whom they see as not worth bothering to do anything.