Is Apheresis an effective treatment for Long Covid and ME?

[Keats]

I had video microscopy taken in 1999 and my blood looked exactly like that in the second slide. The Dr found it interesting (!) but had no idea how to sort it out. Subsequent blood tests for other conditions have had Drs saying ‘there’s something wrong with your blood but we don’t know what it is’, none of them pursued it. Needless to say I’ve been bedbound for nearly 30 years so, though I’m totally unscientific, all this is fascinating and exciting for me. Where do we go from here?

 

[lenora]

Mild Suggestion: That everyone read the latest from Dr. John Chia....you'll see many of these issues addressed in his studies/observations.

@Shanti1 was kind enough to post the entire conversation for all of us. You'll find it under New Post Activity...and may address some of your questions. Don't give up if you think it's all about enteroviruses. Also, please note that he mentions the Brain Donor Project....something I've been looking for and was actually able to register for online.

Also note that a lot of new drugs are coming out as a response to COVID....even before people develop serious symptoms. These drugs may help a lot of you. Worth listening to. Thanks @Shanti1. Yours, Lenora

 

[andyguitar]

Where do we go from here?

To a clinic that can provide this treatment... If you think it would work on you. If that sounds a bit sarcastic it's not ment to. Just want to make the point that although all this is interesting nobody will know if it will work unless they try it.

 

[junkcrap50]

Apparently, the tests for blood clotting don't detect it. Asad said his tests didn't, yet his blood is so thick it has clogged the machine a number of times.

Would the tests from Hemex Labs that was developed to detect problems in ME/CFS's blood, showing hypercoaguabiility and thick blood in me/cfs patients, show anything in Long Covid? That lab is no longer around as it was bought out and stopped offering the ME/CFS thick blood panel. But apparently some of those tests are available today from one lab in germany: https://cfsremission.com/2020/04/15/hemexs-isac-panel-for-me-cfs-is-available/ It would be interesting to see how those results look in long covid and if they are consistent with previous me/cfs research using these tests.

New research indicates that an overload of various inflammatory molecules, literally "trapped" inside insoluble microscopic blood clots (micro clots), might be the cause of some of the lingering symptoms experienced by individuals with Long COVID.

Random thought. Could these microclots be part of the "something in the blood" that Ron Davis found? I don't know the relative size of these microclots vs what he found. Could they be the carriers for whatever is inside, the miRNA or cytokine or virus fragment?

 

[Shanti1]

To reveal if coagulopathies relate to the course of COVID-19, we examined 255 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about ¼ of cases were associated with high levels of C-reactive protein and antiphospholipid antibodies, which impeded coagulation in vitro. Contraction of blood clots was hindered in about ½ of patients, especially in severe and fatal cases, and correlated directly with prothrombotic parameters. A decrease in platelet contractility was due to moderate thrombocytopenia in combination with platelet dysfunction. Clots with impaired contraction were porous, had a low content of compressed polyhedral erythrocytes (polyhedrocytes) and an even distribution of fibrin, suggesting that the uncompacted intravital clots are more obstructive but patients could also be prone to bleeding. The absence of consumption coagulopathy suggests the predominance of local and/or regional microthrombosis rather than disseminated intravascular coagulation. The results obtained (i) confirm the importance of hemostatic disorders in COVID-19 and their relation to systemic inflammation; (ii) justify monitoring of hemostasis, including the kinetics of blood clot contraction; (iii) substantiate the active prophylaxis of thrombotic complications in COVID-19. https://www.nature.com/articles/s41598-021-95397-6

I am not sure how this relates to my comment about microclots in COVID patients being different from other coagulopathies. The difference is noted, not so much in the formation, but the observation that COVID microclots are very resistant to normal breakdown by the body's natural enzymatic processes. This is based on the work of Dr. Pretorius who authored this paper that brought the micro-clot issue into the public eye. The second half of this video:

also goes over the unique nature of COVID clots (seems the fibrinogen mixed with spike protein is what causes the increased resistance to breakdown). I'm not saying that HELP apheresis couldn't be helpful for pwME, as it removes clotting factors as well as bacterial toxins (makes me think of the CBIS theory of ME), but that our micro-clots may not be as resistant to breakdown.

As I tend to do it seems i've started turning this over in my mind and looking for pattern mismatches etc.
I don't think i'm done yet but so far I've thought of a few things. Stress - tends to make people worse, this would line up with a narrowing of the blood vessels. Restless legs or body - mechanical stimulation of the muscles etc might help to shift reluctant red blood cells through the system ? PEM could simply be the result of 'running' the cells under hostile conditions ... mild to moderate lack of oxygen ? possible lack of other nutrients too ? we would expect to see increases in lactic acid under these conditions, which we do. That would explain why mild or moderates don't get PEM at 'rest', the oxygen supply is sufficient in that scenario but insufficient during exercise. Crashes and loss of stamina could either be when the toxicity in the cells becomes too much for too long of a period, or other factors amplify it, causing the cells to go on strike en masse while they regenerate / die off and regrow, this seems like a good fit for ' pacing well over time improves stamina '. The other explanation is that crashes happen when more red blood cells become deformed or however this process is occurring, which means that you feel really ill and have to rest, I suppose the question is wouldn't that turn the person a little more blue in color ? Lastly if the immune system has a hand in creating these issues or 'micro-clots', it would explain why my crashes are much worse when environmental factors in the air are also involved.

Great thought process, I have to think this is definitely a part of the ME pathology.

I would ask (as I have before) why blood cells become deformed. Is deformity a genetic or epigenetic condition such as sickle cell or spherocytosis? Deformed blood cells cannot transport oxidant. Are died-off cells, like spherocytosis, become waste (micro clots) that lingers and clots blood vessels? “The irregular shape of the red blood cells can cause the spleen to break them down faster. A normal red blood cell can live for up to 120 days, but red blood cell with hereditary spherocytosis might live for as few as 10 to 30 days.

Good question. I tend to think it is acquired through some trigger since most of us weren't born with ME and in twin studies often only one twin develops ME. Looking at the literature, it seems the deformity makes the RBC a bit flatter than usual and less flexible. The authors of this paper theorize that this is due to the higher levels of reactive oxygen species found in RBCs of pwME.

Apparently, this isn't enough for the spleen to remove the RBCs, otherwise, we would see hemolytic anemias, increased bilirubin, and falsely deceased HbA1Cs. The authors of this paper theorize that the change in RBC

In ME, the RBCs may be completely normal, and able to deform appropriately. But what if the micro-thrombi circulating with them are sufficient to impede their passage through the smallest capillaries? This would mean the RBCs don't get damaged, but are slow.

You may be interested in this paper which describes the actual physical changes in the RBCs of pwME: https://ashpublications.org/blood/a...rocyte-Deformability-As-a-Potential-Biomarker. So maybe it is a combo.

Also, coagulopathies tend to be associated with increase ESR and pwME have a decreased ESR. Low ESR is actually the most consistent biomarker for ME found yet (Cort has a nice write-up here).
Interestingly, blood hyperviscosity syndromes of all types result in a low ESR. Low RBC deformability is one cause hyperviscosity:
https://www.researchgate.net/public...cosity/link/0c960531ed0dd3724f000000/download (download the free full text)

Joshua Leisk now has 40 blood samples from patients after getting a variety of vaccines and has seen the red blood cell clustering and lack of red blood cell repelling each other - also in some samples the red blood cells look very strange...not perfectly round that is. He even saw what I think might now be fibrin about 4 weeks ago in one of the first ever samples, I thought it looked very odd the first time I saw it, but now I think it looks very similair to a micro clot (the micro clot article published an image of the micro clot and the two look incredibly similair).

Blood clots with low platelets is considered a rare side-effect for both AstraZeneca and J&J vaccine, but it makes sense to question if it could make matters worse for us on a more subtle level than what would be picked up by major adverse event reporting. Logically, any inflammatory state can aggravate a clotting situation because it increases fibrinogen.

I'm in the US so I can't really comment on the AstraZeneca vaccine, but I have seen a lot of labs now done post-vaccination and it is not uncommon to see high WBCs and high CRP (sometimes even up toward 100) in the week after vaccination, slowly returning to base-line over a month. Unfortunately, haven't seen any with fibrinogen or ESR measurements, but that would be interesting to look at too.

 

[Shanti1]

Would the tests from Hemex Labs that was developed to detect problems in ME/CFS's blood, showing hypercoaguabiility and thick blood in me/cfs patients, show anything in Long Covid? That lab is no longer around as it was bought out and stopped offering the ME/CFS thick blood panel. But apparently some of those tests are available today from one lab in germany: https://cfsremission.com/2020/04/15/hemexs-isac-panel-for-me-cfs-is-available/ It would be interesting to see how those results look in long covid and if they are consistent with previous me/cfs research using these tests.

Your post brings up a good point, the importance of the right testing because not all studies looking for hypercoagulable states in pwME have found a correlation (ref). The tests used in the study by Dr. Berg and on his ISAC panel are: Fibrinogen, Prothrombin Fragment 1+2, Thrombin/ AntiThrombin Complexes, Soluble Fibrin Monomer, and Platelet Activation by flow cytometry. He also found anti-B2GPI antibodies. These are a different set of tests than used by the study I referenced that found no correlation, and probably a different set of labs than what we would get if we ask our doctor to test us for hyper-coagulation.

In relation to what this tests look like in Long-COVID patients, I know that docs here are now testing Long-COVID patients for fibrinogen, d-dimer and PT/PTT, but I doubt the others in the ISAC panel are regularly run. Since most of the markers listed (not sure about Soluble FIbrin Monomer) are elevated in acute COVID, I would guess that, if the clotting issue is persisting in Long-COVID, these markers could still be elevated, those perhaps at a lower level than the accute phase (ref)(ref).

 

[Martin aka paused||M.E.]

Ok, to sum it up in my understanding:

Viruses like EV and SC19 might create proteins that are recognized by the platelets in a manner that cause blood coagulation. That seems to be a piece of the puzzle.
Viruses can cause excessive fibrin production. That eventually leads to accumulation. It builds fibrin blocks. These affect blood flow and lead to hypoxia in some parts (tissues, nerves) of the body.
This should lead to fermentation (lactate) due to anaerobic metabolism (although it should be noted that many pwME have low pyruvate pointing towards problems with glycolysis).
The response of the immune system to the pathogens additionally produce inflammation (epithelial inflammation that damages the cells).
Furthermore, the pathogens produce proteins that due to molecular mimicry let the body produce AAB.

The big??? is what is P.E.M. Is it low ATP (bc of hypoxia) being used up or do we have to think along the inflammatory axis: Stressors like exercise as potent stimulators of the innate immune response( IL-6, MIF) Any preexisting immune dysfunction would be revved up/restarted including autoimmune triggers.....?!?

I would not expect apheresis to cure this problem but being a highly effective treatment if it's the hypoxia route. And maybe both are very much linked together.

 

[SWAlexander]

Your post brings up a good point, the importance of the right testing because not all studies looking for hypercoagulable states in pwME have found a correlation (ref). The tests used in the study by Dr. Berg and on his ISAC panel are: Fibrinogen, Prothrombin Fragment 1+2, Thrombin/ AntiThrombin Complexes, Soluble Fibrin Monomer, and Platelet Activation by flow cytometry. He also found anti-B2GPI antibodies. These are a different set of tests than used by the study I referenced that found no correlation, and probably a different set of labs than what we would get if we ask our doctor to test us for hyper-coagulation.

In relation to what this tests look like in Long-COVID patients, I know that docs here are now testing Long-COVID patients for fibrinogen, d-dimer and PT/PTT, but I doubt the others in the ISAC panel are regularly run. Since most of the markers listed (not sure about Soluble FIbrin Monomer) are elevated in acute COVID, I would guess that, if the clotting issue is persisting in Long-COVID, these markers could still be elevated, those perhaps at a lower level than the accute phase (ref)(ref).

Dr. Resia Pretorius Ph.D. and Professor Lobster will join, Dr. Jaeger in her lab in Nov, to demonstrate how difficult it is to dissolve this cloth. (6 min into the video

)
I also asked Dr. Asad Khan if there was an explanation of what these clots & fibrin from his blood consist? That would be the most important finding. I also asked Dr. Jaeger the same question in an email, hoping to get an answer.

 

[SWAlexander]

this is a very important question.
GPCR-specific autoantibody signatures are associated with physiological and pathological immune homeostasis: https://www.nature.com/articles/s41467-018-07598-9

 

[godlovesatrier]

The cat is really amongst the pigeons now isn't it! Nice to see people questioning things publicly to make sure some due diligence is carried out. The quality assurance person in my loves this ha!

 

[andyguitar]

The big???

The big ??? for me @Martin aka paused||M.E. is what would make some people more likely to get me/cfs if it's a blood/circulatory disorder? A pre existing abnormality with the circulatory system perhaps? If yes then the persons medical history would provide a clue.

 

[SWAlexander]

The cat is really amongst the pigeons now isn't it! Nice to see people questioning things publicly to make sure some due diligence is carried out. The quality assurance person in my loves this ha!

Hi godlovesatrier. I don’t understand the phrase “The cat is really amongst the pigeons now isn't it!” Dr. Polster is only asking if it would take out the GPCR because of the TLR9 inhibitor (a drug).

 

[Shanti1]

The big ??? for me @Martin aka paused||M.E. is what would make some people more likely to get me/cfs if it's a blood/circulatory disorder? A pre existing abnormality with the circulatory system perhaps?

I am thinking that the RBC low deformability issue and the sub-clinical coagulopathy develop in response to the ME trigger (whatever that may be) and altered immune signaling. Thinking if we were born with these issues we would all develop ME early and identical twins would both have it. Inflammation and pathogens can lead to higher coagulation states. The authors in the RBC deformability paper think the lack of RBC flexibility develops because of the higher level of reactive oxygen species found in RBC of pwME. I also found @godlovesatrier post on live blood cell analysis interesting, it shows us that RBCs can change their physical characteristics/behavior based on their environment. I'm definitely open to other views and debate, we are all trying to figure this out together.

The big??? is what is P.E.M. Is it low ATP (bc of hypoxia) being used up or do we have to think along the inflammatory axis: Stressors like exercise as potent stimulators of the innate immune response( IL-6, MIF) Any preexisting immune dysfunction would be revved up/restarted including autoimmune triggers.....?!?

I like your summary .
I wish I knew the answer to your million-dollar question.... all of the above.....and then some?

 

[Martin aka paused||M.E.]

more likely to get me/cfs if it's a blood/circulatory disorder?

Since I think the fibrin problems are a consequence and not the cause we are still at the beginning with your question: I think it's not a genetic haplotype. I think it's an accumulation of stressors (”hits”) to the immune system (infections, injuries etc) and that everyone can get it

 

[godlovesatrier]

Agree with Martin. Suspect it's another downstream symptom. But amazing to find.

Although I'd like more information about this patient who had ME who's gone into remission. Do we have anymore details? Validating ME patients who've gone into remission seems so tricky no matter the treatment. Which we all know already

Maybe someone will have a little more info on person x

 

[SWAlexander]

Shanti1 "Thinking if we were born with these issues we would all develop ME early and identical twins would both have it."
You may like to read this study:
A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Differ in Physiological Parameters and Gut Microbiome Composition
https://pubmed.ncbi.nlm.nih.gov/27721367/
or https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058431/

 

[SWAlexander]

Since I think the fibrin problems are a consequence and not the cause we are still at the beginning with your question: I think it's not a genetic haplotype. I think it's an accumulation of stressors (”hits”) to the immune system (infections, injuries etc) and that everyone can get it

"I think the fibrin problems"
I think you are right. If Apheresis could clean up the accumulated garbage in my blood and could fully function again, that would be a winner to me. I know I can´t change my Genes unless CRISPER cast 9 is working on all methylation.

 

[Reading_Steiner]

I haven't had time to look through this properly but are we saying that long covid could be caused by the vaccinations ? if its reliant on the spike protein to cause these micro clot then how would that be the case in long covid where the virus is presumably already dead and gone ? Did Dr Asad Khan take the vaccination ?
people have been recommending to take NAC to treat covid for a while now.

 

[Martin aka paused||M.E.]

I haven't had time to look through this properly but are we saying that long covid could be caused by the vaccinations ? if its reliant on the spike protein to cause these micro clot then how would that be the case in long covid where the virus is presumably already dead and gone ? Did Dr Asad Khan take the vaccination ?
people have been recommending to take NAC to treat covid for a while now.

Hypercoagulation seems to be caused by both. A friend of @godlovesatrier and me as a researcher who studies vaccine injuries and it's the same picture under the microscope of blood clots

 

[SWAlexander]

I haven't had time to look through this properly but are we saying that long covid could be caused by the vaccinations ? if its reliant on the spike protein to cause these micro clot then how would that be the case in long covid where the virus is presumably already dead and gone ? Did Dr Asad Khan take the vaccination ?
people have been recommending to take NAC to treat covid for a while now.

I don't think micro clots are caused by vaccinations. I had micro clots in the arms (PICC line) after every surgery in 2012 and the last in 2016 in addition to thrombosis in the legs. (Factor V Leiden) The PICC line was plugged up every day and had to be flushed out and I became very nauseous when they flushed.
Inherited hypercoagulable conditions include:

• Factor V Leiden (the most common)
• Prothrombin gene mutation
• Deficiencies of natural proteins that prevent clotting (such as antithrombin, protein C and protein S)
• Elevated levels of homocysteine
• Elevated levels of fibrinogen or dysfunctional fibrinogen (dysfibrinogenemia)
• Elevated levels of factor VIII (still being investigated as an inherited condition) and other factors including factor IX and XI
• Abnormal fibrinolytic system, including hypoplasminogenemia, dysplasminogenemia and elevation in levels of plasminogen activator inhibitor (PAI-1 )
  https://my.clevelandclinic.org/health/diseases/16788-blood-clotting-disorders-hypercoagulable-states