Is Apheresis an effective treatment for Long Covid and ME?

[Martin aka paused||M.E.]

How do you interpret this compared with your symptoms?

I think you know, CIRS usually has high MMP-9. I'm also curious if you relate your low reading to any of your symptoms.

I did the test bc I was looking for CIRS. I was very confused about the low results. But after reading in combination with my high LDL and Lp-LPA2 values it makes sense thinking of apharesis.
I think it’s responsible for many symptoms like muscle weakness.

 

[MonkeyMan]

When I listed: https://forums.phoenixrising.me/thr...r-long-covid-and-me.85939/page-5#post-2373071 I hoped somebody gets in. Did you contact the Braun Clinik?

Yes, and I just received a reply:

Unfortunately there are not HELP apheresis machines available in the US. Nevertheless there are some B. Braun Centers in Germany, which provide apheresis therapy. Please have a look at the following website:
https://www.bbraun.de/de/produkte-u...-blutbehandlung/help-lipoproteinapherese.html
In case there is any further question, please do not hesitate to contact us.

 

[SWAlexander]

Martin one more about muscle weakness and oxygen LDL.
"Marked narrowing in the coronary arteries, which are responsible for bringing oxygenated blood to the heart, can produce symptoms such as the chest pain of angina and shortness of breath, sweating, nausea, dizziness or light-headedness, breathlessness or palpitations."
Just got this very interesting article: Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.055340

 

[keepontruckin]

I see there are a couple of clinics in Switzerland that offer this inuspheresis. The Swiss Mountain Clinic seems to be run by dear Dr. Klinghardt who used to and probably still runs the clinic in Washington state for lyme disease. I think people who go there should be interviewed to ensure real improvements happen.

 

[Martin aka paused||M.E.]

Martin one more about muscle weakness and oxygen LDL.
"Marked narrowing in the coronary arteries, which are responsible for bringing oxygenated blood to the heart, can produce symptoms such as the chest pain of angina and shortness of breath, sweating, nausea, dizziness or light-headedness, breathlessness or palpitations."
Just got this very interesting article: Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.055340

You say it’s normal. I say it’s a hint because of low MMP-9 and endothial inflammation

 

[perrier]

Yes, and I just received a reply:

Unfortunately there are not HELP apheresis machines available in the US. Nevertheless there are some B. Braun Centers in Germany, which provide apheresis therapy. Please have a look at the following website:
https://www.bbraun.de/de/produkte-u...-blutbehandlung/help-lipoproteinapherese.html
In case there is any further question, please do not hesitate to contact us.

Thank you. Looks like a good number. But the key issue here is: will this treatment really help ME patients. Up until now, we have heard of a handful, and these are successful. (But folks, Rituximab, ozone, Valcyte etc etc also helped a handful of patients.) Why are the ME researchers/doctors are not responding to this whole issue--I guess with grants allocated the wheels just turn: I really don't know. But desperation exists in every household with a sick family member.

 

[SWAlexander]

You say it’s normal. I say it’s a hint because of low MMP-9 and endothial inflammation

Sorry, I don´t think it is normal. I have a hint that we all starve for oxygen and don't really know why.

 

[Pyrrhus]

I pulled the full-text study written about at Health Rising and it ALSO took an at-rest baseline venous oxygen saturation in the pulmonary artery (SmVO2) reading. The at-rest readings in those with ME/CFS were NORMAL, as in between 60-70%. It was only during exertion when the SmVO2 reading became abnormal (higher than it should be), showing low oxygen extraction.

Unexplained exertional intolerance associated with impaired systemic oxygen extraction
https://link.springer.com/article/10.1007/s00421-019-04222-6

You may be interested in this updated study from the same authors, which suggests that the circulatory problems in ME, from impaired blood flow to the brain, to poor oxygen extraction in the muscles, can all be explained by dysautonomic peripheral arterio-venous shunting:

Insights from Invasive Cardiopulmonary Exercise Testing of Patients with ME/CFS (Joseph et al., 2021)
https://forums.phoenixrising.me/thr...patients-with-me-cfs-joseph-et-al-2021.82907/

 

[Shanti1]

You may be interested in this updated study from the same authors, which suggests that the circulatory problems in ME, from impaired blood flow to the brain, to poor oxygen extraction in the muscles, can all be explained by dysautonomic peripheral arterio-venous shunting:

Yes, thank you. In this additional cohort, oxygen extraction during exercise either decreased in ME/CFS or matched controls (SvO2 was either the same as or higher than controls during exercise). SvO2 was not found to be lower than controls. So consistent with the previous study.

The findings of the first study to directly measure pulmonary and systemic blood flow and gas exchange and small-fiber metrics in ME/CFS generate the hypothesis that peripheral vascular dysregulation causes ME/CFS’s major symptom—exertional intolerance. As in POTS, there appear to be low and high pulmonary blood flow physiological subtypes, the latter associated with impaired peripheral oxygen extraction

.

 

[SNT Gatchaman]

suggests that the circulatory problems in ME, from impaired blood flow to the brain, to poor oxygen extraction in the muscles, can all be explained by dysautonomic peripheral arterio-venous shunting

If I've got this right, they're suggesting that the local vasomotor control fails and there is consequent shunting A-V (bypassing capillaries). They indicate some of this due to small fibre neuropathy.

I guess that could explain the 24-48 hour delayed PEM scenario. But thinking about this micro-clot finding has me more wondering about exertion inducing further occlusion of the capillary bed and delayed RBC transit, as more potential pathways are compromised by larger numbers of now poorly deformable RBCs.

If the capillary bed is viewed as a (very) large potential space, presumably RBCs randomly transit channels and leave some clear at times of rest. O2 diffusion is still OK for tissue needs, at rest. With exertion, more blood flow and RBCs start transitting all possible capillary pathways. Passage is impeded or even blocked in more and more of these capillary pathways.

We have diseases of venous and arterial thrombosis/occlusion. Perhaps this disease is a dynamic capillary occlusion syndrome. Orthostatic intolerance may be because of an effective reduction in blood volume, related to this. Dysautonomia might be a form of central overdrive, attempting to compensate for the poor response to arteriolar control of the vascular bed at the next (capillary) level.

As has been pointed out SFN occurs in diabetes etc and PEM is not a feature as far as I'm aware.

I wonder if the SvO2 goes very low to start with, but then normalises (or goes higher) as the metabolic derangements settle in and tissues compensate for the slow RBC transit speeds.

 

[Pyrrhus]

If I've got this right, they're suggesting that the local vasomotor control fails and there is consequent shunting A-V (bypassing capillaries). They indicate some of this due to small fibre neuropathy.

You've got it exactly right. Except that the small fiber neuropathy (SFN) could be seen as either a cause OR a result of the dysautonomic peripheral arterio-venous shunting. (Small nerve fibers are fed by capillary beds too, and they are particularly susceptible to loss of blood supply.)

I guess that could explain the 24-48 hour delayed PEM scenario.

Remember that Systrom's work only looks at exercise intolerance, not at PEM. The link between exercise intolerance and PEM is still frustratingly unclear. But if the muscles are damaged by insufficient oxygen during exercise, then it might also lead to delayed-onset muscle soreness (DOMS). DOMS usually occurs 1-2 days after the muscle damage, so it might be a contributing factor to PEM.

If the capillary bed is viewed as a (very) large potential space, presumably RBCs randomly transit channels and leave some clear at times of rest. O2 diffusion is still OK for tissue needs, at rest. With exertion, more blood flow and RBCs start transitting all possible capillary pathways. Passage is impeded or even blocked in more and more of these capillary pathways.

That sounds eminently plausible.

a form of central overdrive, attempting to compensate for the poor response to arteriolar control of the vascular bed at the next (capillary) level.

Also eminently plausible. But note that the dysautonomic peripheral arterio-venous shunting is presumed to be primarily modulated by impaired constriction of veins, not by impaired arteriolar control. The walls of these veins are much more compliant than the walls of similarly-sized arteries, and therefore contribute much more to the A-V shunting.

As has been pointed out SFN occurs in diabetes etc and PEM is not a feature as far as I'm aware.

Yes, SFN is a symptom of many conditions. Important to keep this in mind.

 

[EtherSpin]

I don't know how it would be practiced at the needle. It would be interesting though to see the results before and after apheresis

Sorry I wasn't clear as should have been. I mean for example tilting the team towards trying more of the drugs that effect clotting factors and other items filtered by the process to see if this cellular efficiency of the sodium detoxification

 

[SNT Gatchaman]

The late Dr Les Simpson(New Zealand) did work on blood(sticky?) in 1980/90s and connections to ME &CFS. .He died in 2015.

Another link relevant to the discussion of red blood cell morphology and deformability from the noted NZ ME researcher Les Simspon (I think he lectured me back in the day but can’t be sure). It was published in 2010 on an integrated health website. In case not already mentioned, he also published a book in 2012.

ETA: have just purchased the book

 

[Pyrrhus]

the noted NZ ME researcher Les Simspon

Also by Les Simpson:

Blood Rheology and Myalgic Encephalomyelitis: A Pilot Study
Leslie O. Simpson1, B. I. Shand1 and R. J. Olds1 1Pathology Department, University of Otago Medical School, Dunedin, New Zealand
Pathology 1986, Vol. 18, No. 2 , Pages 190-192
http://informahealthcare.com/doi/abs/10.3109/00313028609059457 (need to sign in)

Red cell shape changes following trigger finger fatigue in subjects with chronic fatigue and healthy controls.
Simpson L.O, Murdoch J.C, Herbison P.
N Z Med J 1993;106:104-7.

 

[Shanti1]

You may be interested in this updated study from the same authors, which suggests that the circulatory problems in ME, from impaired blood flow to the brain, to poor oxygen extraction in the muscles, can all be explained by dysautonomic peripheral arterio-venous shunting:

Also eminently plausible. But note that the dysautonomic peripheral arterio-venous shunting is presumed to be primarily modulated by impaired constriction of veins, not by impaired arteriolar control. The walls of these veins are much more compliant than the walls of similarly-sized arteries, and therefore contribute much more to the A-V shunting.

I understand the proposed mechanisms of impaired aerobic capacity in the "Low, Low-Normal, and High-flow" groups and I don't doubt that dysautonomia plays a role in compromised blood flow in ME/CFS, but it seems the authors were more broadly applying proposed small-fiber neuropathy mechanisms than warranted by the 31% who had it. Also, there was an assumption that ME/CFS patients will have the same abnormal innervation to arterio-venous shunts found in some fibro patients (18 out of 24 according to the study cited). In my mind dysautonomia is part of the picture, but may not be exactly as described by the authors. I also wonder if low RBC deformability could also significantly contribute to low oxygen extraction and high SvO2. ( I think hypercoagulation would be more likely to lead to low SvO2).

I'm also not clear how they ruled out mitochondrial dysfunction as a possible mechanism for the low oxygen extraction (@Pyrrhus do you understand this). The authors state:

It has been hypothesized that MM underlies exercise intolerance in a subset of patients with ME/CFS, whose hallmark during incremental exercise is an increased Qc/VO2 slope. Possibly the inclusion criteria of PLF undermined our ability to detect patients with MM and an increased Qc/VO2 slope. There was no evidence of intracardiac left-to-right shunting at the time of the resting right heart catheterization. Together these exclusions leave systemic microcirculatory dysfunction (impaired oxygen delivery to muscles) as the presumptive mechanism.

But didn't the "High Flow Group" have an increased Qc/VO2 slope?

I was also mulling over why only the High-Flow group showed statistically significant low oxygen extraction (seems the other groups were trending that way). Do you think it is possible that in the Low-Flow and Low-Normal Flow groups: Lower venous return --> lower cardiac output would result in lower tissue perfusion and lower SvO2. So perhaps the "Low and Low-Normal Flow Groups" also have difficulty extracting oxygen, but visibility to this is occluded by the greater oxygen extraction due to lower perfusion and slower flow of blood through the capillaries?

 

[Pyrrhus]

I understand the proposed mechanisms of impaired aerobic capacity in the "Low, Low-Normal, and High-flow" groups and I don't doubt that dysautonomia plays a role in compromised blood flow in ME/CFS, but it seems the authors were more broadly applying proposed small-fiber neuropathy mechanisms than warranted by the 31% who had it.

Yes, in my opinion the article is poorly written and appears to implicate the small fiber neuropathy as the CAUSE of the dysautonomia, which, while plausible, is speculative.

It seems much more likely to me that the small fiber neuropathy is a RESULT of the dysautonomia, not a cause. That is, the loss of blood flow to the capillary beds leads to the death of the small nerve fibers. This interpretation would be better supported by their skin biopsy findings.

I'm also not clear how they ruled out mitochondrial dysfunction as a possible mechanism for the low oxygen extraction (@Pyrrhus do you understand this).

I'm not sure that they ruled it out. From my reading, they acknowledged mitochondrial dysfunction as a possible contributing factor to the impaired oxygen extraction. They simply said that their methodology could not support or rule out this possibility.

One of the big problems in their methodology is their use of a convenience sample in the patient selection process, which probably lead to a selection bias or two.

So perhaps the "Low and Low-Normal Flow Groups" also have difficulty extracting oxygen, but visibility to this is occluded by the greater oxygen extraction due to lower perfusion and slower flow of blood through the capillaries?

I think that could well be accurate.

 

[Shanti1]

@Pyrrhus Thank you so much!!

To add to the RBC deformability studies, here is a study confirming that reduced RBC deformability indeed inhibits oxygen uptake, and off-loading, in addition to tissue perfusion.

Effects of erythrocyte flexibility on microvascular perfusion and oxygenation during acute anemia
https://journals.physiology.org/doi/full/10.1152/ajpheart.00109.2007

RBC flexibility appears to be a critical factor in ensuring microvascular function as well as ensuring efficient oxygen uploading in the lungs and offloading in the tissue.

 

[SWAlexander]

How Apheresis Gave Emma Her Life Back

 

[SNT Gatchaman]

Related post on Sex-Specific Characteristics of the Microcirculation.

 

[perrier]

This is an interview with Dr B Prusty. (Not sure it goes here. Moderators can move it, if required.) But there is a chart he shows during the interview where he highlights the differences between LC and CFS/ME. I include it because the question at issue is will ME patients benefit from Aphaeresis.