Is Apheresis an effective treatment for Long Covid and ME?

[andyguitar]

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

My suggestion is for Dr Weir and other interested parties to get together with USA researchers for funding from the US Gov. Not much chance of getting funding from UK Gov.

 

[Shanti1]

I started taking Bromelain 500mg in the morning and in the afternoon Lumbrokinase 20mg.

Seems important to include bromelain specifically if you suspect Long-COVID like clots.

We know from Dr Pretorius's research that Long-COVID clots are high in alpha-2-antiplasmin, which confers the resistance to break down from the body's fibrinolytic enzymes.

It turns out alpha-2-antiplasmin is a serine-proteases inhibitor (ref) (ref). Nattokinase, serrapeptase, and lumbrokinase are all serine-proteases, however, bromelain is a Cysteine Protease, so it could possibly be more effective against an antiplasmin laden clot.

Bromelain has been shown to have antifibrotic activity (ref)

Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin (Aug 2021)

 

[Shanti1]

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.

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.

Of course, n=1 data can have value, which is why medical journals will accept case studies for publication. They basically say, "hey, there may be something here worth further investigation". However, establishing the finding in other with ME/CFS is necessary to know if the results can be more broadly applied, or if they are unique to you. This is even more important when the current literature (showing high SpVO2 in ME/CFS) runs contrary to your n=1.

If you were able/willing to get a muscle biopsy, and it demonstrated Long-COVID type micro-clots, even in an n=1, that would seem like a seminal finding (as long as you haven't also had symptomatic or recent COVID). Someone posted earlier in this thread on the exact method used to detect these clots, I didn't look at it in-depth, but it seems it requires some special processing and equipment.

If you can't get formal approval/funding for a study, maybe you can still informally gather data as opportunities present themselves? Gathering individual data over time, if done correctly can still provide powerful information. I still, think it would be important to get BP, pulse, Oxygen saturation, and respiration. Since low BP can cause low SpVO2 and hyperventilations can cause high SpVO2, it is important to have that data so you know those aren't the cause of an altered SpVO2 reading. Oxygen saturation will rule out lung pathology as the cause of low SpVO2.

It is also important to establish if any ME/CFS patients you are looking at have also had COVID, as that would cloud your results.

 

[dylemmaz]

does anyone know if pentoxifylline would be contraindicated in something like the microclot theory?

i have a script sitting right in front of me that i’ve yet to try. it should theoretically help with tissue oxygenation and red blood cell viscosity, as well as improving blood flow, and i’ve read potentially helps the body in its ability to break down blood clots. good idea or bad? thoughts?

 

[Shanti1]

does anyone know if pentoxifylline would be contraindicated in something like the microclot theory?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228656/

Pentoxifylline and its applications in dermatology
Pentoxifylline affects almost all factors responsible for blood viscosity and is among the first known hemorheologically active drug.[6] The primary hemorheological effects of pentoxifylline are caused by increased red blood cell deformability and decreased blood viscosity. The possible mechanism by which this is achieved involves increased erythrocyte adenosine triphosphate and other cyclic nucleotide levels.[7] Pentoxifylline leads to the inhibition of thromboxane and increase of prostacyclin synthesis. Hypercoagulability states improve because of decreased platelet aggregation and adhesion; increased plasminogen activator, plasmin and anti-thrombin III; decreased fibrinogen, alpha 2-antiplasmin, alpha-1 antitrypsin and alpha-2 macroglobulin.[3] Furthermore, pentoxifylline increases leukocyte deformability, inferring the possibility of a greater role of polymorphonuclear leukocytes in whole blood viscosity.[8,9] Thus, it can be considered as an almost complete rheological drug.[10]

Looks indicated to me for pretty much every blood abnormality discussed on this thread.
Only thing I saw is that it can decrease NK cell activity, but when you look at it as a whole, it seems worth trying. You could take something like AHCC to support NK cells while taking it, if you felt so inclined.

 

[Shanti1]

@dylemmaz I haven't read it yet, but you might be interested in this thread:
https://forums.phoenixrising.me/thr...ent-immunesupresive-agent-your-opinion.82559/
According to the title, perhaps the immune issue is a concern.
Of course, you can always try it and if you feel better, even if you decide not to stick with it, at least you will have gathered important information which can tell you what to focus on.

 

[andyguitar]

good idea or bad? thoughts?

How about staring with a very small dose to see how you get on?

 

[dylemmaz]

How about staring with a very small dose to see how you get on?

i’m prescribed 400mg once a day. this is already quite a low dose! i will report back with any improvements, since i think it is quite relevant to the conversation. thank you for the advice @andyguitar

and thank you for your expertise @Shanti1

 

[SNT Gatchaman]

If you were able/willing to get a muscle biopsy, and it demonstrated Long-COVID type micro-clots, even in an n=1, that would seem like a seminal finding (as long as you haven't also had symptomatic or recent COVID). Someone posted earlier in this thread on the exact method used to detect these clots, I didn't look at it in-depth, but it seems it requires some special processing and equipment.

I believe we have the special processing, equipment and background expertise. I hope to be able check my blood next week. We should also be able to make sure we can successfully re-create the Pretorius technique and confirm our accuracy. There may also be a more simple method coming that she's working on (important for the clinical application). If we show micro-clots in my blood, I'll proceed to a bit of self-sampling of muscle — I thought anterior thigh.

This is even more important when the current literature (showing high SpVO2 in ME/CFS) runs contrary to your n=1.

We'll run a nucleocapsid antibody test and maybe some clever B cell evaluation to confirm whether I was Covid or not. I'm six months post Pfizer-2 and 11 months in to my POTS/atypical ME illness, so would characterise myself as "early-phase". My conjecture is that "late-phase" ME patients compensate for continued micro-circulation impairments and develop increasing numbers of short AV collaterals. It's possible that this process happens to some degree after each PEM event and over time the SvO2 goes up due to the shunting. Agree very important to look at long-term ME patients if possible.

Agree very important to capture the cardiorespiratory and haemodynamic changes with this. Maybe best to do as a formal CPET protocol in that case.

 

[Martin aka paused||M.E.]

I haven't done measurements regarding 02 saturation. But I obviously have problems with fibrin. And it might be micro clots.
MMP-9 is an enzyme that breaks down fibrinogen. IL-1b is a cytokine that binds to fibrinogen.
Lp-PLA2 is very high and shows endothelial inflammation. It binds to LDL.

 

[Martin aka paused||M.E.]

I haven't done measurements regarding 02 saturation. But I obviously have problems with fibrin. And it might be micro clots.
MMP-9 is an enzyme that breaks down fibrinogen. IL-1b is a cytokine that binds to fibrinogen.
Lp-PLA2 is very high and shows endothelial inflammation. It binds to LDL.
View attachment 45460
View attachment 45462

Regarding the normal O2 saturation in ME studies Asad says here that this has NO meaning re micro clots > it's a non-specific parameter

 

[rmbotica]

@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.

I'm in Auckland and was about to reach out to Dr Anna Brooks about these HELP theories. Have you spoken to her? Let's collaborate.

 

[Countrygirl]

There is an interesting Radio interview in French on FB with this post beneath (I don't think it is on Youtube yet):

TUN-ENDCOV, a 100% Tunisian scientific study has just solved the mystery of #COVID_long. This Tunisian multicentric study has finally found an explanation for these persistent symptoms and even indicates a treatment!
Several teams of doctors and researchers have collaborated on this study. We called the 2 leaders to talk about it:

Pr LEILA ABID Pr in cardiology at CHU Hédi Chaker de Sfax, Past President of the Tunisian Society of Cardiology and Ardiovascular Surgery

Pr SALEM ABDESSALEM Pr aggregated in cardiology, former treasurer of the #STCCCV.

The midday is yours from #RTCI with Donia Chaouch from April 15, 2021

The gist of the interview is that in LC (and ME) there is severe damage to the endothelium and the drug S U L O D E X I D E reverses this and restores health.

I gather that this medication is not available in many countries such as the UK and France.

 

[Martin aka paused||M.E.]

The gist of the interview is that in LC (and ME) there is severe damage to the endothelium and the drug S U L O D E X I D E reverses this and restores health.

I think a combination of apheresis and BC007 could cure or at least treat this disease as well (I mean ME)

 

[Countrygirl]

Interesting tweets:

Resia Pretorius
@resiapretorius
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.

@doctorasadkhan
and
@oabuhamad
SCD40L is a platelet activation marker, but not necessarily of microclots?
Resia Pretorius
@resiapretorius
·
Nov 4
Hyperactivated platelets and microclots are both important - the 1 drives the other. Both these 2 pathologies must be addressed to assist the inflamed endothelial layers to heal. In longcovid endothelialitis is a significant pathology.
Show replies
Lorry
@Lorry15896818
·
4h
Replying to
@resiapretorius

@doctorasadkhan
and
@oabuhamad
If anyone has been wondering why statins and grams of nicotinic acid sometimes (lots of times actually!) work for long covid. Biofilm and cell wall membrane. G'day and Good luck!!
ncbi.nlm.nih.gov
The Significance of Lipids to Biofilm Formation in Candida albicans: An Emerging Perspective
Candida albicans, the dimorphic opportunistic human fungal pathogen, is capable of forming highly

https://pubmed.ncbi.nlm.nih.gov/34140635/
Online ahead of print.
Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?

Stefan R Bornstein 1 2 3 4, Karin Voit-Bak 5, Timo Donate 5, Roman N Rodionov 6, Raul R Gainetdinov 7 8, Sergey Tselmin 6, Waldemar Kanczkowski 6, Gregor M Müller 6, Martin Achleitner 6, Jun Wang 6, Julio Licinio 9, Michael Bauer 10, Allan H Young 11, Sandrine Thuret 12, Nicole Bechmann 6 13 14 15, Richard Straube 5


Lorry
@Lorry15896818
·
4h
Replying to
@resiapretorius

@doctorasadkhan
and
@oabuhamad
Asad&Resia, just search for babesiosis+IDC or/and babesiosis+coagulation+dogs and I guarantee you will have a good day!To make it even better search Candida as well for gastro based long Covid.I took Fluconazole, Artemisinin+Iron& Monolaurin and the improvements are by the day
charlos
@loscharlos
·
Nov 3
Replying to
@resiapretorius

@doctorasadkhan
and
@oabuhamad
So to clarify, a Thromboelastography (TEG) would not be sufficient?

Resia Pretorius
@resiapretorius
·Nov 3
TEG is an excellent point of care method! It tests blood clotting and a method we use all the time in the lab.
charlos
@loscharlos
·
Nov 3
Nice! But can it detect the micro clots found in #LongCovid ?
Resia Pretorius
@resiapretorius
·
Nov 3
It can detect the consequences of microclots and hyperactivated platelets in blood - in its various parameters. Thus it will immediately light up clotting issues.
charlos
@loscharlos
·
Nov 3
So would this test be a sufficient bio marker for #LongCovid microclots? From my understanding most major hospitals have this testing available correct?
Resia Pretorius
@resiapretorius
·
Nov 3
It will most definitely confirm clotting issues.
charlos
@loscharlos
·
Nov 3
@doctorasadkhan
sounds like Thromboelastography (TEG) would be sufficient biomarker ? This is available at most large hospitals.

There were a few people on slack talking about ordering this test, it being first abnormal lab, and using it to request anticoagulants.
Dr Asad Khan FRCP FRACP
@doctorasadkhan
·
Nov 3
Correct me if I’m wrong
@resiapretorius
but TEG is just evidence of clotting issues rather than microclots per se? Can be deranged for multiple reasons.

Resia Pretorius
@resiapretorius
·Nov 3
TEG looks at clotting parameters that include the reaction time, which is time to start of clotting - to the strength of the clot and clot breakdown. It shows both pathological clotting, as well as bleeding propensity. Microclots may interfere with clotting and noted with TEG.

 

[aquariusgirl]

I had high T/AT complexes on ISAC panel. Hm.

 

[Shanti1]

The gist of the interview is that in LC (and ME) there is severe damage to the endothelium and the drug S U L O D E X I D E reverses this and restores health.

Sulodexide looks like an interesting medication (aka Aterina). It is 80% low molecular weight heparin and 20% low molecular weight chondroitin. What makes it unique is that almost all heparin is given either IV (regular heparin) or subcutaneous injection (low molecular weight heparin) and this is an oral formula. Here is an informative post on the research on the use of heparin in ME/CFS.
https://livingwithchronicfatiguesyndrome.wordpress.com/2016/08/23/heparin-for-me/
It seems worth trying, too bad Sulodexide may be hard to get a hold of.

TEG looks at clotting parameters that include the reaction time, which is time to start of clotting - to the strength of the clot and clot breakdown. It shows both pathological clotting, as well as bleeding propensity. Microclots may interfere with clotting and noted with TEG.

Take home on TEG: it can tell you if you have a clotting problem (microclots included), but not if you specifically have resistant long-covid type micro-clots.

 

[JES]

Just taking blood thinning drugs like pentoxifylline or fibrinolytic enzymes will likely not be enough. Lots of people tried those supplements a decade or two ago following the hypercoagulation hypothesis of Dr. Berg (ref).

I trialed bromelain several years ago with some very interesting effects. I noticed a massive relief of my brain fog a couple of hours later and a subtle weird feeling as if my legs were in a shower. I realized this was all from the improved blood flow.

The problem with taking bromelain or other blood thinning supplements was that I consistently began to feel worse a day or two later following continuous use. Ramped up flu-like symptoms and POTS, etc. I think this would fit nicely with the idea that you can try to dissolve those blood clots and probably succeed, but ultimately the misbehaving protein or antibody that remains in the blood still does its damage unless you do something like apheresis.

 

[Martin aka paused||M.E.]

Just taking blood thinning drugs like pentoxifylline or fibrinolytic enzymes will likely not be enough. Lots of people tried those supplements a decade or two ago following the hypercoagulation hypothesis of Dr. Berg (ref).

I trialed bromelain several years ago with some very interesting effects. I noticed a massive relief of my brain fog a couple of hours later and a subtle weird feeling as if my legs were in a shower. I realized this was all from the improved blood flow.

The problem with taking bromalin or other blood thinning supplements was that I consistently began to feel worse a day or two later following continuous use. Ramped up flu-like symptoms and POTS, etc. I think this would fit nicely with the idea that you can try to dissolve those blood clots and probably succeed, but ultimately whatever protein or antibody that remains in the blood still dose its damage unless you do something like apheresis.

Yes, Asad said you have to remove them manually.

 

[perrier]

https://www.tlcsessions.net/episodes/episode-18-professor-resia-pretorius-microclots

Interview with Dr. Pretorius; very informative. She said that she will start the ME study in January. ( But I read on twitter that when Dr Pretorius comes to Germany next week, there will be some ME patients there. But it is hard to verify things on twitter. Someone in the know please post.). Also, in this interview Dr. P. states that it is Dr Proal who is indicating to her that ME is also likely due to microcloting. Another interesting point she highlighted was that she said some researchers in Yale found that the virus was lodged also in the gut, and they speculated that the spike proteins gets released from there too and that could be driving Long Covid. This would overlap with ME, as some folks have enterovirus in their GI tract (as found by Dr. Chia.).

Last night I also listened to the interview noted above @Countrygirl ; and the thesis there is that the endothelial lining is damaged and needs to be healed. I liked the way the Doctor kept likening the lining of capillaries to Teflon.

The issue for us, however, is : is all this pertinent to ME? Thanks everyone for a very interesting thread.