Is me/cfs a blood disorder?

SNT Gatchaman

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Consul

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@SNT Gatchaman A couple of questions on the micro clot theory. Wouldnt there be a marked prevalence of cold hands/feet in me/cfs patients if there were micro clots going on? And dont you think the micro clots would sometimes lump together forming clots in e.g the head or lungs, so that me/cfs patients would have a marked prevalence of hospitalization because of these conditions?
 

SNT Gatchaman

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Wouldnt there be a marked prevalence of cold hands/feet in me/cfs patients if there were micro clots going on?
I think the idea is that the micro-clots are taking effect at the capillary level (reducing oxygen diffusion to tissues) and at the red-cell level (impairing their deformability and transit through capillaries). This is all theoretical currently. The micro-clots aren't occluding larger vessels, sufficient to cause eg limb ischaemia.

You might get cold peripheries at times though, related to the POTS changes which I suspect are failed compensations for the micro-circulation issues.

And dont you think the micro clots would sometimes lump together forming clots in e.g the head or lungs, so that me/cfs patients would have a marked prevalence of hospitalization because of these conditions?
At this time we don't know that micro-clots are the problem in ME (but the symptom overlap is so striking, that it has to be related). There's obviously something very special about the micro-clots — they've only recently been appreciated, so presumably tend not to cause clinically obvious DVT, stroke etc.

One possibility is that they are present in the early phase of the disease, i.e. the earliest long Covid is only just over 18 months. Perhaps they clear but persistent / late-phase ME is because of long-standing effects on the micro-circulation. (I was wondering about induced short capillary AV shunts for example.)

Much yet to learn, but this seems incredibly promising to me. I hope we are able to show micro-clots in ME. One way to almost immediately answer the question is if the nano-needle technique gave a positive result without the monocytes in the sample. Then we'd be pretty confident that the long term ME patients they were testing (with high specificity) were due to micro-clots (the "something in the blood").
 

Shanti1

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I keep seeing conflicting information about lab testing. Is there any agreement yet on tests that might help indicate something's wrong?
@junkcrap50

The tests I posted are the ones that I could find where there are studies on pwME showing coagulation abnormalities. Standard coagulation tests are generally normal in pwME (PT/PTT, D-Dimer, fibrinogen). There is also a study showing low RBC deformability in pwME, but that isn't looked at on standard testing. Microclots are, as of yet, unproven in ME/CFS.

Thromboelastography (TEG) has been shown to be abnormal in acute COVID. I didn't see any studies on TEG in Long-COVID, but it seems it would be abnormal if it is being proposed as a method to monitor therapy in Long-COVID.

I didn't find studies on TEG in pwME. However, this study, which looked at clotting pathways, platelet aggregation, and whole blood aggregation (not TEG technique exactly, but looking at similar parameters), did not find increased clotting in pwME.
 

Shanti1

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My thought is that there are issues with clotting and RBCs in pwME, but I am skeptical that the same microclots seen in Long-COVID are occurring in ME/CFS. The COVID virus, specifically the S1 portion of the spike protein, has been shown to induce severe clotting pathology in acute COVID and to alter the structure of fibrinogen so that clots are resistant to break down.

Most pathogens associated with ME/CFS are not associated with severe coagulopathy. You can find a case here and there, but it isn't like COVID where it is a primary feature. I personally think that pathology would have been detected prior as microthrombi aren't a new phenomenon, just put in the spotlight by COVID-19.

Where I am seeing a connection is that pwME and Long-COVID tend to be positive for some of the same antiphospholipid antibodies, which are associated with a higher likelihood of clots.
https://www.science.org/doi/full/10.1126/scitranslmed.abd3876
https://pubmed.ncbi.nlm.nih.gov/10695770/
https://paolomaccallini.com/2016/07...e-anti-cardiolipin-antibodies-and-mast-cells/
 
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Except... standard blood tests in ME are normal. No evidence of intravascular haemolysis, circulating inflammatory mediators etc.
But I'd say it's unlikley that someone suffering the early symptoms of me/cfs would (in the UK) have much in the way of blood work done. And if they did get any tests done at a later stage the RBC abnormalities might have resolved themselves leaving the damage undetected.
 

Shanti1

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I am happy to be proven wrong on the microclots, as it would be great to have something concrete to target, but that is my current take. What we need is the microclot detection as described by Dr. Pretorius to be performed on pwME for a definitive answer. Hopeful these tests will be performed on pwME who have not had COVID so as not to confuse the issue.

It is also possible that a subset of people with ME have microclots, but given the vast number of ME triggers, it is hard to imagine that all do. I am also of the mindset that blood clotting/RBC issues are only one of many facets in ME/CFS
 
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Most pathogens associated with ME/CFS are not associated with severe coagulopathy.
And it is not certain as to what percentage of cases started with an infection.
I am also of the mindset that blood clotting/RBC issues are only one of many facets in ME/CFS
I'd agree that micro clots might not be found in all cases but I'd be suprised if RBC abnormalities were not. Just going on what Ron Davis et al found.
 

Shanti1

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I'd agree that micro clots might not be found in all cases but I'd be suprised if RBC abnormalities were not. Just going on what Ron Davis et al found.
You may be right on that. Linking to the paper below so others can reference it.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398549/

Edit: low RBC deformability is thought to be due to increased oxidative stress. In my mind, it is probably one of many downstream effects from the ME/CFS trigger and is something acquired post-ME/CFS.
 

Shanti1

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More on the "something" in the plasma reported by Ron Davis:

Induced pluripotent stem cells as suitable sensors for fibromyalgia and ME/CFS (Monzón-Nomdedeu et al., 2021)

https://www.wjgnet.com/1948-0210/full/v13/i8/1134.htm
In support of the “ME/CFS-specific plasma factor” reported by Ron Davis and his team at Stanford University, CA, United States, Elisa Oltra´s team at the Catholic University of Valencia, Valencia, Spain, in collaboration with Karl Morten´s group at Oxford University, Oxford, United Kingdom, found that cellular oxygen consumption was altered upon addition of ME/CFS human plasma (unpublished, preliminary data). The impact of ME/CFS plasma on the respiration of the muscle cell line used as reported in the assays mentioned above is believed to reflect the altered metabolic status of the patients.
This indicates something inhibiting mitochondrial function beyond RBC deformation and clots.

Paper first was posted by Pyrrhus here:
https://forums.phoenixrising.me/thr...-and-me-cfs-monzon-nomdedeu-et-al-2021.85271/
 

Oliver3

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Sounds like science fiction! How about a more ordinary explaination of what might be going on. Like this....me/cfs starts with the formation of abnormal red blood cells. These are broken down in the vascular system (intravascular hemolysis) releasing inflammatory chemicals (including free hemoglobin) leading to dysfunction of the circulatory system and it is this dysfunction that causes symptoms. Red blood cell abnormalities can be caused by: Some drugs, nutritional deficiencies, infection, excessive exercise, Radiotherapy and probably metabolic disorders. EDIT you dont need micro clots for any of the above.
Ha..no, the open med foundation were looking into the electrical fields in mitochondria I believe. As I understand it, you need protons to move down the electron chain and through mitochondria.
I don't discount anything your saying but we all run on electricity. Hence the fashion for grounding etc.
The fact that the omf were looking at mitos and electricity I found strangely compelling.
Kruse does delve into sci fi.
He asserts that autoimmunity is mainly a modern day phenomena resulting from electricity.
Whilst I have no ability to deconstruct his argument, it does sound a bit far fetched. That said. We can't rule anything out.
His belief is that all the healthy eating protocols, standard naturopathic, allopathic models miss out the importance of us as electrical beings
 

Oliver3

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Sounds like science fiction! How about a more ordinary explaination of what might be going on. Like this....me/cfs starts with the formation of abnormal red blood cells. These are broken down in the vascular system (intravascular hemolysis) releasing inflammatory chemicals (including free hemoglobin) leading to dysfunction of the circulatory system and it is this dysfunction that causes symptoms. Red blood cell abnormalities can be caused by: Some drugs, nutritional deficiencies, infection, excessive exercise, Radiotherapy and probably metabolic disorders. EDIT you dont need micro clots for any of the above.
https://www.nih.gov/news-events/nih-research-matters/muscle-mitochondria-may-form-energy-power-grid

Here's what I was reffering to . This idea that electrical fields play an important role in our MiTo and muscle health
 

Shanti1

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ATP is also involved in that deforming process......
Wow, it sure is: https://www.frontiersin.org/articles/10.3389/fphys.2018.00656/full

Also found that RBC deformation stimulates capillary dilation, so if they don't deform, it could further compromise blood flow:
Red Blood Cell Deformability, Vasoactive Mediators, and Adhesion (McMahon 2019)
Thus, RBC deformation is an important stimulus for ATP export from RBCs and allows them to dilate arterioles and readily traverse capillaries that are in some cases smaller in diameter than the RBC itself.
Another factor to consider is altered phospholipid metabolism in ME/CFS, which could alter the RBC cell membrane composition.

I'd agree that micro clots might not be found in all cases but I'd be surprised if RBC abnormalities were not. Just going on what Ron Davis et al found.
Along these lines, low RBC deformability is considered a blood hyperviscosity syndrome and is consistent with the low ESR observed in most ME/CFS patients. This is just more evidence that the low RBC deformability is a consistent theme.
 
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Except... standard blood tests in ME are normal. No evidence of intravascular haemolysis, circulating inflammatory mediators etc. I think the red cells are specifically not broken down — they likely persist for their standard 120 days, but have poor deformability.

The micro-clots are a good explanation for all of this - sequestering activated platelets and inflammatory mediators that are still having biological effects, but hidden from our plasma tests.
Isn't it the case though that normal healthy RBCs also present with poor deformability when exposed to hypoxic conditions? I believe Ron Davis mentioned that in his most recent update.

I'm not sure if microclots are the only potential causative factor but it appears that there is definitely something in the endothelial tissues causing a widespread dysfunction.

I don't know if this rules out things like generalised high levels of oxidative stress or metabolic pathway deficits though - do microclots address why there is widespread collagen breakdown and issues with connective tissues?
 

SNT Gatchaman

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Isn't it the case though that normal healthy RBCs also present with poor deformability when exposed to hypoxic conditions? I believe Ron Davis mentioned that in his most recent update.
According to the posted summary there was a significant difference.

We heard an update on red cell deformability. In previous work, some labs have found a difference in red cell deformability between patients and healthy controls, and one lab found no difference. However, it was recently discovered that oxygen levels in the blood have a major impact on deformability. New instruments are being developed to measure deformability under controlled oxygen levels. There is a clear difference in deformability between patients and healthy controls under low blood oxygen levels. Thus, this continues to provide promise for a fast and inexpensive biomarker and diagnostic test.