The micro-clot finding in Long Covid — implications for the possible aetiology of ME/CFS

[MSEsperanza]

No control group.

 

[Trish]

 

[Andy]

And I'm suspicious when the only results reported by patients, at least on that figure, were "No effect" or "Improved". 91 patients and nobody at all reported worsening of any measure? Again, hopefully the preprint explains this.

 

[Trish]

I think he would be far better just saying there's a preprint of a pilot study coming soon - and that it has no control group and no follow up after stopping the treatment as far as I can see from the tweets.

 

[Robert 1973]

No control group.

I can’t see from the tweets whether there were any objective outcome measures.

Kahn: “These are the fluorescence micrographs of microclots stained with Thioflavin T in 5 patients before (left) & after (right) the course of treatment. These patients had a corresponding good clinical response too.”

So no controls – for a treatment which has had a lot of publicity about its potential benefits – and just 5 patients*. It would be interesting to know it people examining the micrographs were blinded to the “good clinical responses”.

I hope I’m wrong but what I’m reading doesn’t inspire confidence.


[edit: *5 patients in the micrograph comparison graphic.]

 

[Trish]

91 patients, not 5.

 

[Robert 1973]

91 patients, not 5.

Thanks, edited to clarify.

 

[Jonathan Edwards]

The presentation is unprofessional in various respects.

I find it hard to see the ethical justification for giving anticoagulants, which carry significant morbidity and mortality, in a trial that does not look as if it can give any useable results.

 

[Creekside]

When I see results like that, my question is: would that group have had similar results if the treatment was magic crystals or other such things?

 

[Jonathan Edwards]

Depends a bit on the quality of the magic I guess.

One thing I note was that people either showed improvement or 'no effect'.
But since they were likely to have improved anyway maybe improvement is 'no effect'.
And 'no effect' really means failure to improve or worse - quite likely a bad effect.

 

[John Mac]

NHS doctor takes housebound daughter to Germany for Long Covid treatment

A doctor who took her daughter to Germany for treatment after she contracted Long Covid, said the NHS needs to "keep up with the science".

In an interview with ITV Meridian, Dr Binita Kane, NHS Respiratory Consultant said: "I think the NHS is doing its best given the resources that it's been given but if you're going to solve a problem, one of the fundamental issues is to understand the problem you're trying to solve and there hasn't been an acknowledgement that long covid is a multi system, complex, largely vascular disease that is debilitating tens of thousands of children across the country.

"We are stuck in a model where we're giving children rehab and psychological therapies and the NHS isn't keeping up with the science that's rapidly emerged over the last few years that's really helped us to understand what's causing the condition.

"A year ago my daughter, who was then 11, had been housebound for nearly a year with long covid. She was needing a wheelchair for distance and it was absolutely devastating to our family.

"Now, I'm a doctor and a scientist and I just wasn't willing to accept that this level of disability in a previously healthy child was normal and that there was nothing we could do.

"I sought to connect with scientists from across the world and I was really lucky enough to go out to Germany and they were able to look at my daughter's bloods under a microscope and they could see that she had very sticky blood, with clotting abnormalities and it made sense to me that that sludgy blood clogging up her little capillaries were then not able to give oxygen to the muscles and the tissues that she needed.

"She was treated with drug therapy for the abnormalities that were seen and then slowly over 6-8 months she got better. Now, those treatments weren't without some small risks but to me, the risk of doing nothing was far higher at that stage.

https://www.itv.com/news/meridian/2...-daughter-to-germany-for-long-covid-treatment

 

[Jonathan Edwards]

She was treated with drug therapy for the abnormalities that were seen and then slowly over 6-8 months she got better.

That would be very peculiar. If the treatment was some form of removal of clotting factors or clots then you would expect to see improvement immediately that would probably wear off after hours or days. I am not aware of any reason why it should lead to improvement gradually over months.

 

[CRG]

Kane and Chew-Graham publications: https://www.s4me.info/threads/bjgp-...nd-contradictions-by-chew-graham-et-al.27851/ and https://www.s4me.info/threads/bjgp-...tions-by-chew-graham-et-al.27851/#post-468035

"sludgy blood clogging up her little capillaries", those would be the dainty child capillaries as compared to giant adult capillaries !?

There's something very off about a clinician who would otherwise be bound by patient confidentiality, using parental privilege to use their own child as a patient exemplar.

 

[SNT Gatchaman]

I don't think she had apheresis - rather triple anticoagulants following "demonstration" of vascular/haematology pathology. I remember the Twitter thread Binita posted last year, although I had assumed it was apheresis at the time.

From May 2022 —

There's something very off about a clinician who would otherwise be bound by patient confidentiality, using parental privilege to use their own child as a patient exemplar.

I think I recall she indicated that Jasmin herself pushed to discuss publicly, for the potential benefit of other children. This could be viewed similar to how we have more mature children co-sign their surgical consent forms along with their parents. The law requires the parental decision/signature, but from a principle of autonomy and empowerment, co-signing often helpfully assists in the grey zone. In children with long-term conditions, they are often very informed as you might imagine. That is probably off-topic and orthogonal to whether this treatment was correct, and helpful.

Later in the thread, Binita said —

 

[Robert 1973]

days. I am not aware of any reason why it should lead to improvement gradually over months.

And a gradual improvement over 6-8 months is a fairly typical outcome for a child who has had a post-viral syndrome for less than 2 years with no treatment.

For anyone unaware Binita Kane was co-hosting the Independent SAGE meeting in Long Covid with Trish Greenhalgh (see: https://www.s4me.info/threads/united-kingdom-independent-sage.24432/page-4#post-466510)

It’s good that Binita and others at the meeting raised the problems with BPS ME/CFS research and therapies but they undermine their credibility if they do not apply the same critical standards to biomedical research.

I would be delighted if the micro-clots theory proved to have some clinical significance which led to effective treatments becoming available but from my limited understanding we are a very long way from that at the moment. In the meantime desperate and vulnerable patients are being encouraged try expensive unevidenced therapies which are not without risks.

I can understand patients wanting to take those risks – I have tried various experimental treatments in the past – but those taking a lead on LC should be highlighting the issues and calling for more high-quality research instead of promoting unevidenced therapies based on anecdotes and unreplicated studies of questionable significance.

 

[Jonathan Edwards]

I don't think she had apheresis - rather triple anticoagulants following "demonstration" of vascular/haematology pathology.

Interesting point. There is still a query as to why pathology subtle enough not to be visible in terms of physical signs or standard tests would take months to resolve on anticoagulation. Again, I would rather expect rapid improvement at least over a couple of weeks. Resolution of neurological problems with clot lysis occurs pretty immediately.

 

[Robert 1973]

Playing Devil’s advocate here: if someone had been unwell and significantly disabled for 12 months, even if the therapy had an immediate effect on the pathology which was causing the symptoms, is it conceivable that it might still take a few months for the patient to get back to get back to fitness?

I seem to recall that at the Indie SAGE meeting Anthony Costello said he’d tried an anticoagulant for his long covid and that he had noticed his fatigue had subsequently improved. He was careful to add that it was purely anecdotal, and he could not know whether the improvement was due to the treatment, but he said words to the effect that he thought it was worth a try as it was relatively low risk despite being unevidenced.

Is Costello someone you know from UCL Jo?

 

[Jonathan Edwards]

is it conceivable that it might still take a few months for the patient to get back to get back to fitness?

The idea that it might take that long is conceivable. I just cannot at the moment conceive of any mechanism that is likely to apply.

One of the key aspects of credibility of anecdotal evidence from cases or pilot studies is seeing the therapeutic dynamic follow an expected path. Like a dose response curve it turns a single observation into a shape that is far less likely to have occurred by chance.

The theory seems to be postulating what is called diffuse intravascular coagulation (DIC).
DIC is traditionally recognised by one of the most florid skin rashes of all - the sheets of purpura that occur in meningococcal septicaemia. Even in the subacute form secondary to endocarditis tiny infarcts are seen in the nail bed and retina.

A thrombus in a capillary will block it completely - whether child or adult. This is visible. I still don't know what people think the actual pathology is.

 

[Sly Saint]

sticky blood

I remember reports of this for ME from twenty + years ago.

 

[CRG]

A thrombus in a capillary will block it completely - whether child or adult. This is visible. I still don't know what people think the actual pathology is.

Devil's advocate but - if near surface capillaries are not involved, only those associated with internal structures: liver, kidneys, spleen, small intestine - then there could be non-visible disease. Even then organ specific symptomology would surely be evident ? And why the larger fenestrated or sinusoid capillaries and not the smaller continuous capillaries ?