Is Apheresis an effective treatment for Long Covid and ME?

[junkcrap50]

This person with ME/CFS has been on heparin for 4 years and noticed a huge improvement. In a tweet lower down, she says her doctor is with the Holtorf Medical Group. Dr. Holtorf has talked about thick blood and a fibrin layer coating the blood vessels, preventing nutrient and oxygen delivery for many years.

 

[perrier]

This person with ME/CFS has been on heparin for 4 years and noticed a huge improvement. In a tweet lower down, she says her doctor is with the Holtorf Medical Group. Dr. Holtorf has talked about thick blood and a fibrin layer coating the blood vessels, preventing nutrient and oxygen delivery for many years.
View attachment 45653

Yes, Dr. Holtorf has been using heparin for ages and ages, and has talked of thick sticky blood for a long time. He is not invited to ME conferences for some reason. The problem is that a good number of patients have not been able to tolerate the heparin injections.

 

[GlassCannonLife]

Dr Jaeger has updated the pre-apheresis treatment for patients.

Any ideas (anyone) why he is recommending against using the proteolytic enzymes?

 

[GlassCannonLife]

This person with ME/CFS has been on heparin for 4 years and noticed a huge improvement. In a tweet lower down, she says her doctor is with the Holtorf Medical Group. Dr. Holtorf has talked about thick blood and a fibrin layer coating the blood vessels, preventing nutrient and oxygen delivery for many years.
View attachment 45653

Any ideas how fast they noticed the changes? I did 6 weeks of enoxaparin recently and didn't notice any benefits on my ME

 

[BrightCandle]

It could just be the natural flow of the condition but I am having some of the best weeks of the past few years right now, I have a lot more energy. Still on bromelain and lumbrokinase . Would be nice to get to the official drugs of course but well we all know how hard that is as an ME patient doctors being the way they are. Still too early and small progress to be able to say its anything but a blip but I am improving currently after a long plateau after HASD 3.2 and the subsequent crash and recovery.

 

[SNT Gatchaman]

Cheers for posting that @Countrygirl Looks like something that should not be tried without proper medical supervision!

Yes, agree 100%. These are potentially dangerous drugs and they're being used in combination. They would need to be supervised appropriately. I've been aware of this for probably a little longer than most here and I have not self-medicated. I want to be fixed tomorrow, but I am waiting for trial indications of what may be best.

It may be that a gentle return to normal fibrinolytic balance is much better for cellular recovery than going in all guns blazing. The opposite may also be true. We don't yet know.

We also don't know about how this could tie in to long-term ME and optimising recovery potential.

 

[junkcrap50]

Any ideas (anyone) why he is recommending against using the proteolytic enzymes?

Probably because it's complicates the medication dosing and monitoring. You don't know how much of the thinning is coming from the enzymes or drugs. And I don't think there's that much research on them vs drugs. Plus, if you're trying to establish a treatment protocol, these enzymes are not standard across brands/types. Also hard to compare patients if they are at various enzyme dosages, depending how much is in per capsule per brand/etc.

Any ideas how fast they noticed the changes? I did 6 weeks of enoxaparin recently and didn't notice any benefits on my ME

I don't know. I don't have twitter, but if you do, you can ask her on twitter.

 

[Countrygirl]

This may prove not to be relevant but I was reminded of Dr Les Simpson's claim that ME was caused by poor blood flow in the capillaries and the resultant deprivation of oxygen and nutrients. He maintained it was the abnormal, still RBCs in addition to abnormally small capillaries that was the cause.

I ordered his book Ramsay's Disease and have just finished it. I made notes as I read. If anyone is interested, I will put them here.

 

[GlassCannonLife]

This may prove not to be relevant but I was reminded of Dr Les Simpson's claim that ME was caused by poor blood flow in the capillaries and the resultant deprivation of oxygen and nutrients. He maintained it was the abnormal, still RBCs in addition to abnormally small capillaries that was the cause.

I ordered his book Ramsay's Disease and have just finished it. I made notes as I read. If anyone is interested, I will put them here.

That's interesting, thanks for sharing your notes.

I noticed he mentions that when they put the RBCs in saline they revert to a normal morphology - perhaps this is why saline infusions can be transiently helpful?

It's a shame he couldn't get the paper published showing exercise caused a change in RBC shape. Generally if you provide further supporting data then reviewers will accept it (or you can find a different journal). Seems unfortunate that he didn't persist with that? Or did he publish it elsewhere and I missed that?

Also, crazy to see that the other papers where he's talking about this were from 1997 and it hasn't been explored further!

Does he specify a dose of hydroxocobalamin? I have a large bladder of this (500 mL at 2 mg/mL) so I can try as much as seems worthy of experimentation. I normally do 1 mg each morning but that doesn't really give me any significant benefits, maybe a very slight boost in energy.

It does seem in line with the other ME experts though in that he seems to have just chosen a single dysfunction that he is attributing all of the problems to - I wonder if he is right? The data seems promising but then so does a lot of data in ME studies that doesn't seem to translate into clinical outcomes.

 

[andyguitar]

He maintained it was the abnormal, still RBCs in addition to abnormally small capillaries that was the cause.

I've come across the small capillaries idea before (possibly from Dr Simpson) but I think it's a result of the dysfunction rather than the primary cause. An interesting idea though and worth investigation.

 

[SNT Gatchaman]

I ordered his book Ramsay's Disease and have just finished it. I made notes as I read. If anyone is interested, I will put them here.

I am reading this book too. I would be very interested to read your notes and thoughts @Countrygirl. I've been reading through Les Simpson's papers also and I think his findings were and will be very pertinent to working the disease out.

I think that following an immune system event (typically virus, currently SARS-CoV-2) the pathology involves the interplay between —

1. Platelet activation
2. Endothelial inflammation and dysfunction
3. Red blood cell deformability

I expect these factors will self-reinforce and perpetuate the disease into its chronic form (with all other symptoms following from this).

A key term to watch out for in the near future will be "inflammatory - coagulation mediator cross-talk".

 

[andyguitar]

Also, crazy to see that the other papers where he's talking about this were from 1997 and it hasn't been explored further!

I can remember that years and years ago an English High Court Judge started a campaign to try to get the NHS to use Heparin to treat ME ( his daughter had it and got better from Heparin treatment) he didnt have any luck.

 

[SlamDancin]

@SNT Gatchaman My health is currently deteriorating and I’m experiencing a crash as we speak. The symptoms that are very noticeable are a pounding heart beat and a burning feeling in my head and face. Any idea relative to your theory of why these symptoms would occur?

 

[SNT Gatchaman]

I'm very sorry to read that @SlamDancin.
I think the range of specific symptoms we experience when stable and during a crash are very broad. According to this model, many of these symptoms would be downstream to events in the micro-circulation. From a high-level view it may relate to worsened tissue hypoxia.

Let's say a classic PEM episode is induced by walking too far or climbing stairs. This might produce impaired micro-circulation performance in a couple of ways, due to the required higher cardiac output. There might be an accumulation of micro-clots in the capillaries; as well as worsening deformability of red cells. Both could act to reduce the amount of O2 delivered to tissues. The micro-clots may be forced to the periphery of the vessel as RBCs try and squeeze through. This would make a barrier to O2 diffusion (and maybe increase endothelial inflammation).

A "clogged" micro-circulation might lead to compensatory attempts via heart rate and blood pressure changes.

From Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome —

ME/CFS patients may experience altered vascular responses following aerobic exercise, contrary to what is seen in healthy populations. This is thought to be a result of the increased presence of oxidative stress and low-grade vascular inflammation, which may be exacerbated by exercise and contribute to the onset of PEM

I'm only considering the pseudo-macroscopic view above — what might be happening to cells. What's happening within cells, in terms of the altered metabolic pathways is another level to consider.

----
So why hasn't this been discovered before, e.g. post-mortem studies on ME patients? The capillary endothelial inflammatory change may be modest - just taking effect over an entire body network. Platelet activation may be the predominant factor. The micro-clots, even if they were badly clagging the micro-circulation might be invisible.

Post-mortem, the blood coagulates anyway and this occurs quite quickly. It's often been challenging to diagnose if someone died of a thromboembolic event (e.g. PE). I don't think you could detect micro-clots at standard PM, unless you knew to look for them (and we've only just discovered them in living patients).

 

[mariovitali]

@SlamDancin : Sorry to hear this, i hope you feel better soon...

@SNT Gatchaman

I have been using an Information Extraction system to help identify connections between ME-relevant topics.

I am not sure if this is already known but i found that there is a connection between the topics you are looking at and the complement C1Q. The following study identifies C1Q as a marker :

https://www.mdpi.com/2077-0383/10/18/4171


A surprise among the concepts were flavonoids. They appeared to be highly ranked. A bit of searching and i found the following :


https://pubmed.ncbi.nlm.nih.gov/28412372/


In other words, flavonoids appear to be inhibiting platelet aggregation. One other thing i found is that collagen induces platelet aggregation :

Platelet aggregation with collagen

Collagen is the most thrombogenic component of the suben- dothelium (1). Following vascular damage, collagen is exposed to circulating platelets and both acts as a substrate for the adhesion of platelets (2–4) and induces platelet activation (4).

I wonder if this is why EDS (collagen breakdown) + ME/CFS usually co-exist?

 

[SNT Gatchaman]

Thank you for the refs. Yes I think complement will be part of the micro-clot story. The Pretorius paper identified C1 at 25x level between long and acute Covid. C7 was 20x in LC vs controls too.

I wonder if this is why EDS (collagen breakdown) + ME/CFS usually co-exist?

Yes, I really like the way that can hang together. Two platelet receptors respond to collagen exposed from damaged blood vessels (part of the intrinsic pathway of the coagulation system). Not sure if EDS collagen is abnormal, so also more activating in itself, but the vessel walls are more likely to be repeatedly damaged - probably at continuous low level.

I can't yet see how this might tie into CCI - or rather specifically how a fusion might fix the whole disease. Perhaps it's able to just bring the collagen exposure load and overall platelet activation down below the threshold of self-perpetuation. Coupled with the enforced recovery post surgery, maybe that could do it?

 

[GlassCannonLife]

Thank you for the refs. Yes I think complement will be part of the micro-clot story. The Pretorius paper identified C1 at 25x level between long and acute Covid. C7 was 20x in LC vs controls too.



Yes, I really like the way that can hang together. Two platelet receptors respond to collagen exposed from damaged blood vessels (part of the intrinsic pathway of the coagulation system). Not sure if EDS collagen is abnormal, so also more activating in itself, but the vessel walls are more likely to be repeatedly damaged - probably at continuous low level.

I can't yet see how this might tie into CCI - or rather specifically how a fusion might fix the whole disease. Perhaps it's able to just bring the collagen exposure load and overall platelet activation down below the threshold of self-perpetuation. Coupled with the enforced recovery post surgery, maybe that could do it?

Yeah the CCI story is strange, particularly when you see cases that didn't have ME or CCI (like Jen Brea), who then develop CCI gradually through a lack of activity and worsened collagen handling because of ME.. And then are cured by fixing the CCI.? I wonder if they had already been cured from their root cause previously but then the CCI kept their ME around?

 

[junkcrap50]

So why hasn't this been discovered before, e.g. post-mortem studies on ME patients? The capillary endothelial inflammatory change may be modest - just taking effect over an entire body network. Platelet activation may be the predominant factor. The micro-clots, even if they were badly clagging the micro-circulation might be invisible.

Not postmortem studies, but why not biopsies? Could they not see a microclot obstructing a small capillary? You would have to be a bit lucky to catch it, right place right time.

 

[SNT Gatchaman]

Could they not see a microclot obstructing a small capillary? You would have to be a bit lucky to catch it, right place right time.

I (briefly) considered doing this on myself, but I discussed with an anatomical pathologist friend of mine and he thinks it would be pretty challenging even knowing what we were going for. Honestly, I think this will be proven on blood microscopy, cell marker and inflammatory marker studies. A bit of medical imaging may also be able to complement, which I'm going to try and look into.

In the meantime, I think we sit and wait for a few weeks and see what is found with the micro-clot studies that have just started with the South African team in Germany. I am optimistic that we are about to hit the good part of a hockey stick graph with the research - flat for decades due to BPS dominance, but about to take off with new biomedical insight.

 

[Countrygirl]

Just a thought I am leaving here as I am short of time just now, but wouldn't Dr Vance Spence's (MEResearchUK) two papers that discussed the 'severe' endothelium damage his team identified in ME be a relevant part of this discussion? Are they in the PR archive, perhaps?