The Occurrence of Hyperactivated Platelets and Fibrinaloid Microclots in ME/CFS, 2022, Nunes, Pretorius et al

[Mij]

Why are nutraceuticals mentioned?

I hope this doesn't involve taking 'natural' blood thinners (bromelain, nattokinase et), unmonitored, and assuming it's safe. Proper testing might not be available and some pwME will experiment on their own.

I took bromelain as a potential anticoagulant twenty years ago when hypercoagulation was a theory for pwME. I took the supplement for a few months before my blood panel was finalized and it really thinned my blood- I cut my finger once and it wouldn't stop bleeding. When my ISAC panel was finalized it was determined that I didn't have hypercoagulation. The head Hematologist here advised not to assume when taking blood thinners.

 

[DokaGirl]

I have factor V Leiden. This is often described as sticky blood or blood which is more liable to clot in certain circumstances such as immobility following surgery or during long haul air travel. A blood thinner, low molecular weight heparin, is often prescribed in these circumstances to prevent the possibility of clotting.

I have noticed on many occasions that the fatigue/ exhaustion that accompanies ME is significantly better after taking heparin in order to fly, allowing me to function at a higher level than expected. I don't know how or even whether this links with microclots but heparin improves my functioning.

It is a shame Dr Simpson's work from the 90s was not followed up, and that the OMF has not seemed to complete its work on red cell deformability. The latter might not link to microclots but blood related research has been started before and then abandoned. Resia Pretorius has been working very hard on microclots; I hope she has the resources to complete her efforts.

That is very interesting @Binkie4 that you feel better with heparin. It's my recall that David Berg's theory recommended heparin as a therapy.

Yes, agreed, it is very unfortunate that the research on blood for pwME has had such a stalled history. Frustrating, but not surprising given the managed lack of biomedical funding for ME.

 

[DokaGirl]

Since we're all happily speculating here, I'll add another idea to the mix (haven't read the study either, just to be certain I don't know what I'm talking about)

If only a subgroup is affected, could this be because the weird clotting is a corona-specific effect and that the affected ME subgroup just happens to have "very long covid" from one of the common cold coronaviruses circulating?

N=1 Thick, black blood, needles blocking up (that's the big ones like the ones they use for blood donations) and even having the nurses literally pull blood clots out of my veins when removing the needle used to be a regular occurrence for me. The doctor wasn't keen on blood thinners but didn't object to me trying supplements with blood-thinning effect (possibly because he thought they'd be useless?). Anyway, that's what I've been doing since. It's very effective for avoiding the blocked needles, my blood runs much better. Makes no difference to my ME though. And little if any (not sure on this one, definitely not a big effect) to my various symptoms related to capillaries doing strange things.

So I have a sneaky feeling that the whole blood clotting thing may turn out to be a sideshow. But prompt and rigorous replication would be much appreciated

My blood draws sound somewhat familiar to yours, @Ravn, but without the clots. They
have usually/most often been difficult. First to find a vein that doesn't wiggle away. Then finally to find one that at best, very reluctantly gives up blood. It goes better if I have lots of fluid before the blood draw. I sometimes use "blood-thinning" supplements. Surgery is another matter as of course no food or fluid for about 12 hours before the operation. Three times it's taken well over half an hour just to get an anesthetic needle into a cooperative vein.

Yes, I hope this study can be replicated.

 

[Dolphin]

 

[LarsSG]

The results of that figure look like a major difference but the authors reported even larger differences for diabetes type 2 and covid-19 in a 2020 paper:

I'm not sure what's going on, but it doesn't look like these are directly comparable. The controls in that earlier paper showed about five times higher average amyloid area %. So maybe the method was somehow different or maybe the control group was different.

 

[LarsSG]

Looking at their past papers, looks like they are claiming fibrin amyloid formation is present in migraine, T2 diabetes, rheumatoid arthritis, Alzheimer's, sepsis, septic shock, SIRS, and multiple organ dysfunction syndrome, acute Covid, Long Covid and now ME. That's just going off the titles of the papers, so I'm not sure how all these findings compare.

 

[Wyva]

Are there any conflicts of interest?

They haven't listed any this time but from one of the previous papers we know that Pretorius is director of Biocode Technologies.

Info from their website:

Research
We are a team of physiologists and biochemists who do novel research in inflammatory diseases, including cancer, cardiovascular disease and circulating inflammatory biomarkers.

Development
We combine and synergize concepts from the fields of engineering, physics, biochemistry and physiology to develop innovative inflammatory biomarker sensing solutions.

Data Management
We develop data management solutions to optimize the processing of our research and sensor data outputs for medical diagnostics.

Some people from the "Team" section (these people are not among the authors of the paper, I'm just trying to illustrate what the company is doing):

Este Burger (MEng)
Research and Design Engineer
Este completed her Electronic Engineering Master's degree at Stellenbosch University. Her research fields include biosensor design, fluorescence-based sensing techniques and optical design. She specialises in the detection of anomalous fibrin(ogen) clot-formation due to the presence of circulating inflammagens.

Simoné Turner
Physiologist
Simoné Turner completed her honors degree in Physiology at Stellenbosch University. Her research fields include haematology, oncology and pathology. She specialised in blood coagulation, circulating inflammatory markers and how these play a role in inflammatory conditions.

 

[ME/CFS Skeptic]

So maybe the method was somehow different or maybe the control group was different.

Yes could be, I don't know the finer details of the methods but from the outset they look the same. So it could also be that their results are simply all over the place. I mostly posted it because some (e.g Ponting) seemed impressed by the large difference.

 

[MSEsperanza]

It would great if people who are on Twitter could ask some of the questions so that people who are now excited about those findings will see the questions, too.

Especially the questions about the number of patients that actually had clots and whether the samples were blinded?

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I think we really need to see the values on the Amyloid area measure for the individual patients, as it is indicated in the paper that the differences were only found in a subset of patients. So the lower value than in other diseases could be because fewer patients had clotting, or because all those with clotting had it at a lower level, or some mix of the two.

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One thing that perhaps worried me most is that the method section of the paper says nothing about blinding. It indicates that samples were viewed under a microscope and areas selected for image analysis. I am afraid that this is the perfect scenario for observer bias. I used to do this sort of microscopic analysis and it is almost impossible not to be biased if you know what you are supposed to be looking at.

 

[LarsSG]

I also wonder about past Covid being an issue with these results. They say that patients were excluded if they had past Covid infection, but they don't say how and they don't report any serology results (though even that would not be definitive). I imagine in 2022 in South Africa where infection numbers have been very high and testing low, you're likely to have a fair number of people who had Covid and didn't know it in any group of 25 people.

Maybe ME plus recent Covid would give different results than ME alone, potentially helping explain why they found a wide range of results.

 

[TigerLilea]

Surgery is another matter as of course no food or fluid for about 12 hours before the operation.

I had surgery two years ago and they had me have a drink of water before I left for the hospital and they gave me a drink of water about 15 minutes before the surgery. Current thinking is that patients have better surgical outcomes when hydrated.

 

[Helene]

What happens if you have perpetually low platelet counts, and have some issues with clotting? I have ME/CFS and PEM, but I have low platelets, usually out of range low. I wonder if this matters.

Interested in what your investigations find @duncan . I too have below reference range platelet counts.

 

[MSEsperanza]

I've had a nurse shake a vial of fresh blood (mine) in front of me and ask me if it looked right, it was thick, dark, not red, viscous, and had taken her minues to obtain, and looked like tar.

Strange behavior from the nurse. Why would a nurse ask a patient if their drawn blood looked right?

As others reported strange colors, viscous or actually clotting blood in their fresh blood samples, and also nurses that commented on it, did you ever ask the nurses for an explanation?

I mean, if this was very unusual or indicative of an illness, wouldn't nurses either know about it or be more alerted about it and curious to know?

 

[DokaGirl]

I had surgery two years ago and they had me have a drink of water before I left for the hospital and they gave me a drink of water about 15 minutes before the surgery. Current thinking is that patients have better surgical outcomes when hydrated.

I agree. I was told to drink juice first before a surgery that I had 6 years ago.

I'm going soon for another surgery, and I was told no food or fluid for 12 hours before the surgery.

Just this one issue, one of many, shows how slow and patchy the uptake on new and better medical info is.

 

[Jonathan Edwards]

I mean, if this was very unusual or indicative of an illness, wouldn't nurses either know about it or be more alerted about it and curious to know?

It is entirely normal. If blood is taken from a small vein that can only provide a limited supply there is always a risk of clot formation on the needle or in the syringe. Venous blood is dark bluish purple anyway and if flow is slow it is likely to be more de-oxygenated. Colour has nothing to do with clotting.

 

[paolo]

Looking at their past papers, looks like they are claiming fibrin amyloid formation is present in migraine, T2 diabetes, rheumatoid arthritis, Alzheimer's, sepsis, septic shock, SIRS, and multiple organ dysfunction syndrome, acute Covid, Long Covid and now ME. That's just going off the titles of the papers, so I'm not sure how all these findings compare.

It seems that dr. Pretorius is also involved in patents for treatments of blot clots in Alzheimer's disease, Parkinson's disease, and type 2 diabetes (this page, bottom).

 

[Jonathan Edwards]

I agree. I was told to drink juice first before a surgery that I had 6 years ago.

I'm going soon for another surgery, and I was told no food or fluid for 12 hours before the surgery.

Maybe just this one issue shows how slow and patchy the uptake on new and better medical info is.

I don't think there is anything new about this to be honest. Adequate hydration has been a priority at least ever since I was a medical student. It is normally addressed by using intravenous fluid.

 

[JemPD]

series of ostensibly unrelated findings can be cobbled together into a self-consistent narrative - as long as you don't mention the ones that don't fit that is.

Like the BPSers do.

I hope this isnt going to be another blind alley by researchers who want their theories to be correct and are not being rigorous/sceptical enough about them to really interrogate the theory/finding, rather than seeking to prove it.

 

[DokaGirl]

I don't think there is anything new about this to be honest. Adequate hydration has been a priority at least ever since I was a medical student. It is normally addressed by using intravenous fluid.

Thank you @Jonathan Edwards.
The problem I've encountered with 3 various surgeries, is that the medical staff work for quite a while to get any needle into one of my veins. This with surgeons waiting, and the time ticking away.

In 2016, it was new to me to be advised to drink juice before the surgery. Other than in 2016, I've been told nil by mouth before surgery, including this upcoming operation.

I have the same problem with blood tests if I haven't sufficiently hydrated before the tests.
I don't mind needles, but sometimes it takes several tries for one session.

 

[Chris Ponting]

One thing that perhaps worried me most is that the method section of the paper says nothing about blinding. It indicates that samples were viewed under a microscope and areas selected for image analysis. I am afraid that this is the perfect scenario for observer bias. I used to do this sort of microscopic analysis and it is almost impossible not to be biased if you know what you are supposed to be looking at.

Hi Jonathan. I asked Doug Kell about this specifically, and he said that the experimentalists were blinded to case/control status.