Is Apheresis an effective treatment for Long Covid and ME?

[Reading_Steiner]

I await the fruit of your endeavours with anticipation, I tried a Time grape seed extract pill today and i'm not sure what to make of the effect, its not categorically positive, I expected it to barely do anything but it does feel like its made a significant change already. I feel strange but I can't really pin it down to anything specific, a few hours on and I feel more tired if anything super reluctant to do anything and my arms ache. I will wait for more information on this overall topic before I venture to try another go on this.

 

[perrier]

For those who may not have see this. Dr Pretorius says micro clots can be relatively easily detected:

Dr Asad writes: (today)

For those of you who have been asking about microclot detection. There is no marker as of yet, but here is a method by which they can be physically demonstrated #LongCovid #MECFS
Quote Tweet

Resia Pretorius

@resiapretorius
· Oct 30
Replying to @doctorasadkhan and @oabuhamad
Actually to find the microclots in a sample is very simple and fast with the addition of the marker Thioflavin T to plasma - however, a fluorescence microscope is needed. Platelet hyperactivation is seen by adding 1 or 2 fluorescent platelet markers to whole blood.


--------------------------


MY question is: how is it that Stanford has not accommodated Dr. Davis with a fluorescent microscope; or lent him one. How is this possible in America??


Are there no fluorescence microscopes in the USA? Why is Dr. Davis without one? How is it that America/ Stanford cannot provide this researcher with one?

 

[Breagjam]

For those who may not have see this. Dr Pretorius says micro clots can be relatively easily detected:

Dr Asad writes: (today)

For those of you who have been asking about microclot detection. There is no marker as of yet, but here is a method by which they can be physically demonstrated #LongCovid #MECFS
Quote Tweet

Resia Pretorius

@resiapretorius
· Oct 30
Replying to @doctorasadkhan and @oabuhamad
Actually to find the microclots in a sample is very simple and fast with the addition of the marker Thioflavin T to plasma - however, a fluorescence microscope is needed. Platelet hyperactivation is seen by adding 1 or 2 fluorescent platelet markers to whole blood.


--------------------------


MY question is: how is it that Stanford has not accommodated Dr. Davis with a fluorescent microscope; or lent him one. How is this possible in America??


Are there no fluorescence microscopes in the USA? Why is Dr. Davis without one? How is it that America/ Stanford cannot provide this researcher with one?

I agree wholeheartedly. Why is this happening in America. Ron’s son has a fundraiser going on to get Ron a fluorescent microscope - about $15k of the $30k has been raised on the spotfund website, but more $$ may have been donated through sending money to Ron via Stanford

 

[Shanti1]

Not at all, though order not yet submitted. It's the i-STAT Allinity, which is a cartridge based system. We had the CG4+ cartridge in mind. It may be prudent to include Hb and Hct also though. Please let me know if you think we should include other parameters.

Hbg and Hct could be useful since the body may extract more O2 from existing hemoglobin if oxygen delivery is decreased from anemia. Similarly, a polycythemia would cause increased oxygen delivery, and thus decreased oxygen extraction (higher SvO2).
Not sure what your budget is but I wonder if it would be worth including D-Dimer since it is often elevated months after acute COVID and is related to clotting (ref). I'm sure you are also getting an arterial oxygen saturation with pulse ox.

I believe the most accurate studies to date on this are the invasive CPET tests done by Systrom and team which were all on-the-day evaluations, sampling directly from the pulmonary artery (just prior to the lungs) and used controlled exercise on a cycle. This would have moved the lower body, but spared upper body movement.

Although the most accurate, it's too risky to keep a Swan-Ganz pulmonary artery catheter in over days in an awake and mobile patient. Even a short internal jugular central venous line would be too much infection risk for patients and controls, so that to follow the hypothesised descent and recovery over days post-exertion that I'm interested in trying to show, I think we're obliged to go with simple intermittent upper limb sampling. I suspect the swings would be quite marked in patients vs controls (though that remains to be shown).

If you know the limitations of SpVO2 and how to adjust your interpretation, you should be able to detect larger devience from normal, especially if it is really off. I can totally understand the need to go with a periferal draw over the others and think it is great that you are even able to attempt this experiment.

Below is a table from the first of the ME/CFS SvO2 exercise studies:
https://pubmed.ncbi.nlm.nih.gov/31493035/
It sounds like you will be doing your measurements following exertion, but while subjects are at rest, but I thought I would post this anyway. It shows how SvO2 drops during exercise in all groups, but less so in the ME/CFS group (all the poor oxygen extractors had ME/CFS diagnosis). The paper goes through the equation used to estimate oxygen extraction.

(NL=Normal, HV=Hyperventilators, SOEL=serum oxygen extraction with low PvO2, SOEH=serum oxygen extraction with high PvO2)
These were the reasons given for the poor oxygen extraction:

thank you for the advice above re: peripheral SvO2 readings. I was thinking analysis in days following an exercise event, where I would assume normal controls would have returned to normal — for the modest exercising, I had in mind, like a 10-15 minute gentle walk.

In the two ME/CFS studies discussed on this thread, samples were taken prior to exercise and during exercise, but not post-exercise or when PEM may have been occurring. Is your decision to measure post-exercise designed to catch something that the other studies didn't see? "Catch it in the act" so to speak when someone is symptomatic with PEM?
Thanks for your work on this

 

[SNT Gatchaman]

In the two ME/CFS studies discussed on this thread, samples were taken prior to exercise and during exercise, but not post-exercise or when PEM may have been occurring. Is your decision to measure post-exercise designed to catch something that the other studies didn't see? "Catch it in the act" so to speak when someone is symptomatic with PEM?

Yes that is exactly what I'm thinking about. I'm looking to capture evidence that suggests PEM might be associated with further impairment of RBC capillary transit - causing increased time for more oxygen extraction.

In that scenario, PEM might be less about tissue hypoxia in solid organs (in fact they'd have more O2), but may be more about hypoxia for circulating white blood cells and the haemodynamic changes related to a "traffic jam" in the capillary beds (of muscle, gut, brain etc).

It might even be that different forms of PEM occur when the inciting blood flow increase is occurring due to physical exercise, digestion or cognitive effort.

There may be better ways to evaluate this but off-the-cuff I can't see how e.g. a red cell-labelled scintiscan could differentiate. And apart from the PEM, this is not particularly risky to do.

 

[wabi-sabi]

It might even be that different forms of PEM occur when the inciting blood flow increase is occurring due to physical exercise, digestion or cognitive effort.

This sounds very interesting to me. How so many different types of effort can cause PEM has always been a point of confusion.

 

[Shanti1]

Yes that is exactly what I'm thinking about. I'm looking to capture evidence that suggests PEM might be associated with further impairment of RBC capillary transit - causing increased time for more oxygen extraction.

In that scenario, PEM might be less about tissue hypoxia in solid organs (in fact they'd have more O2), but may be more about hypoxia for circulating white blood cells and the haemodynamic changes related to a "traffic jam" in the capillary beds (of muscle, gut, brain etc).

It might even be that different forms of PEM occur when the inciting blood flow increase is occurring due to physical exercise, digestion or cognitive effort.

There may be better ways to evaluate this but off-the-cuff I can't see how e.g. a red cell-labelled scintiscan could differentiate. And apart from the PEM, this is not particularly risky to do.

So if SvO2 is significantly lower than controls in your experiment, and we also consider the previous at rest/exercise SvO2 studies as valid, it would show two different mechanisms for poor oxygenation in ME/CFS: 1. Poor oxygen extraction at rest and during exercise (high SvO2) due to mito dysfunction or capillary shunting related to dysautonomia and 2. Poor oxygenation during PEM due to low tissue perfusion and slower blood flow (low SvO2) resulting from possible hypercoagulation/micro-clots. If your experiment shows SvO2 similar to controls, then, even though we know clotting is a problem at some level, mechanism one is likely more predominant in all phases (at rest, exercise and PEM). That is how I'm thinking about it anyway.

This is stating the obvious, but BP, pulse, and respirations are important data to have as well.

 

[SNT Gatchaman]

This is stating the obvious, but BP, pulse, and respirations are important data to have as well.

Thank you again! Yes, and the POTS aspect is intriguing. I don't know if we would have sufficient accuracy in the blood tests to correlate P/BP changes with SvO2 on following days, but it's tantalising. In which case, we should probably go for lying-standing assessments too. That might be a clue to a (functional?) reduction in blood volume.

Gosh if we had decent numbers in a study, then the next level would be demonstrating an associated drop in cerebral blood flow.

This is starting to look like it might need a Systrom-type evaluation after all! I'm trying to gather the right people here, so early days.

Just to link for this thread, if not previously referenced on PR: on-the-day studies have been done before, as above and e.g. in this ME CPET paper presented at the IACFS-ME conference a couple of months ago.

 

[Countrygirl]

For those on Facebook, there is a group set up called Patient Initiative -Apheresis for Long Covid.

It might be interesting to join the more than 2000 members there for information and discussion.

 

[Countrygirl]

Nice Tweet from Asad:





Dr Asad Khan FRCP FRACP #FBLC

@doctorasadkhan

Trudie Chalder & Co stop whining. You’re pathetic. Exit now. Stop claiming graded exercise therapy is helpful when 67% of patients say it makes them worse. And don’t even think about turning your attention to #LongCovid! #MECFS #MyalgicEncephalomyelitis



meassociation.org.uk
Dr Shepherd’s rapid response to BMJ Article | The ME Association
ME/CFS: Exercise goals should be set by patients and not driven by treatment plan, says NICE Patient reports of harm from GET cannot be ignored Dear Editor Professor Trudie Chalder … Dr Shepherd’s...

 

[Countrygirl]

https://scitechdaily.com/overload-o...-H7RTwSgUnCAsn7InK4A8m2ZXEJmxGBYWkRHtVRjzTxXc

A simple introduction to the subject.

First evidence of inflammatory micro clots in blood of individuals suffering from Long COVID: This may be the cause of some of the lingering symptoms experienced by individuals with Long COVID.

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.


This unexpected finding was made by Prof Resia Pretorius, a researcher in the Department of Physiological Science at Stellenbosch University (SU), when she started looking at micro clots and their molecular content in blood samples from individuals with Long COVID. The findings have since been peer-reviewed and published in the journal Cardiovascular Diabetology in August 2021.

“We found high levels of various inflammatory molecules trapped in micro clots present in the blood of individuals with Long COVID. Some of the trapped molecules contain clotting proteins such as fibrinogen, as well as alpha(2)-antiplasmin,” Prof Pretorius explains.

Alpha(2)-antiplasmin is a molecule that prevents the breakdown of blood clots, while fibrinogen is the main clotting protein. Under normal conditions the body’s plasmin-antiplasmin system maintains a fine balance between blood clotting (the process by which blood thickens and coagulate to prevent blood loss after an injury) and fibrinolysis (the process of breaking down the fibrin in the coagulated blood to prevent blood clots from forming)........................................

 

[Countrygirl]

Here is Asad talking in detail about microclots and H.E.L.P. apheresis.

 

[BrightCandle]

There was a paper posted some pages back suggesting some anticoagulent drugs and supplments to try before getting HELP Apheresis so 4 days ago I started taking Bromelain 500mg in the morning and in the afternoon Lumbrokinase 20mg. IIRC the paper suggested it was 2 months before I would know if it was helping so I am not anticipating anything of note to occur yet. I did however before starting do a lancet test of my blood flow, pretty thick lucky to get a blob out for a glucose/uric acid test.

I squeezed out 3 times as much as normal today and it took a couple of goes for it to clot afterwards. Small amounts of progress and my blood is still thick but thinner than it was. So from that perspective there is a noticeable change already in that test, a very clear one. I don't feel any different otherwise, within the usual variance at the moment.

 

[Countrygirl]

Flushing niacin is a blood thinner and breaks down fibrin. Patients are taking it and a friend of mine who has worked up to 250 mg a day, split into 50mg dose, says it has improved her severe ME symptoms by 20%.

 

[perrier]

I read somewhere that Dr Proal is indicating that money needs to be raised for Dr. Pretorius to do the ME study using Apheresis. Dr. Pretorius will be in Mulheim in a week or so and she wanted to do the ME study after that. Does anyone have any news about what is happening with this? Thanks very much.

 

[SNT Gatchaman]

@Shanti1 I wrote out a draft research proposal along the lines that we've been discussing up-thread. It's being looked at by two of our local researchers in NZ over the next few days and hopefully they'll be able to consider its merit. I'm not an experienced researcher so of course my thoughts on this may be naive. I'll let you know if they can eliminate any foolishness and think it could fly. (They are very relevant and credible researchers).

While I'm spit-balling —

If a population study is not realistic, I was wondering a little more about what you could do by investigating a single patient (me) that potentially had less constraints (ethics etc). This is along the lines of the precision medicine studies that Warren Tate among others have talked about.

OMF have a pre- / post- PEM muscle biopsies project, which might be able to pick-up micro-clot even if that wasn't the initial specific intent. But while we're waiting on that...

If you were going to go to the trouble of inducing (even mild) PEM, why not check bloods before and days after for micro-clot burden along with a series of e.g. thigh muscle biopsies. Might be day 0, day 2, day 4, day 7. Imagine demonstrating an increase and then decrease in intramuscular capillary micro-clot, or the reverse pattern, even at n=1.

 

[BrightCandle]

Flushing niacin is a blood thinner and breaks down fibrin. Patients are taking it and a friend of mine who has worked up to 250 mg a day, split into 50mg dose, says it has improved her severe ME symptoms by 20%.

I have a long hauling friend who is taking B2 and the Selenium et et for the formulation stack and its definitely improved things. I thought the theory behind that was DNA damage causing deficiency in B2 however. Didn't help me but has helped them and its quick to act too, you know in a day or two.

 

[SNT Gatchaman]

I read somewhere that Dr Proal is indicating that money needs to be raised for Dr. Pretorius to do the ME study using Apheresis. Dr. Pretorius will be in Mulheim in a week or so and she wanted to do the ME study after that. Does anyone have any news about what is happening with this?

Nothing more than was discussed in the video up-thread, but I expect there will be plenty of coverage on this on social media that we can track.

Social media may end up quite important to this whole effort, esp. if they are after funding. On the back of Hannah Davis's patient-led Long Covid studies, I'm getting a sense of a modern incarnation of the moon-shot, but this time, instead of a Kennedy, it's all the patients saying "we choose to ... do the other things".

 

[Countrygirl]

I have a long hauling friend who is taking B2 and the Selenium et et for the formulation stack and its definitely improved things. I thought the theory behind that was DNA damage causing deficiency in B2 however. Didn't help me but has helped them and its quick to act too, you know in a day or two.

The improvement from B3/flushing niacin is rapid too and takes just two or three days for a noticeable improvement, according to friends who have tried it.

 

[Countrygirl]

Nothing more than was discussed in the video up-thread, but I expect there will be plenty of coverage on this on social media that we can track.

Social media may end up quite important to this whole effort, esp. if they are after funding.

Christoph Strock, who has very severe ME, I understand, has said on Twitter that he is offering to fund worthwhile research. He has already donated £50000 to Maureen Hanson to research enteroviruses. I emailed Dr Weir who passed the message on to Asad. I don't know if they have now got in contact and what the outcome might be.

Tweet

Christoph Ströck
I have great respect for
@DrMaureenHanson
and her work in #mecfs. I awarded 50k USD to her lab to look into Enteroviruses' potenial role in pathology of pwME . Why am I telling you this? /1


@cstroeckw

I have great respect for
@DrMaureenHanson
and her work in #mecfs. I awarded 50k USD to her lab to look into Enteroviruses' potenial role in pathology of pwME . Why am I telling you this? /1