Positive Health Online

Introduction

There are thousands, potentially millions of people who have Long Covid.  Effective treatments are still being sought by researchers.

The main cause of death in Covid is microclots in the lungs and other organs.[1]

Dr Amy Proal has shown the occurrence of microclots in ME/CFS.[2]

Long Covid has as many as 150 possible symptoms, many of which overlap with the symptoms of ME/CFS. Professor Resia Pretorius has said, in her interview with Dr Amy Proal (Minute 13)  that all of these could be explained by lack of oxygen. [See YouTube Reference below]. The formation of microclots in both Covid and Long Covid causes blockages in the microcirculation which lead to this oxygen deprivation.

LO Simpson did research into changes in the shape population of red blood cells in chronic conditions, and noted that in these conditions, the proportion of non-deformable red blood cells increased.  As these non-deformable cells cannot get through the microcirculation, he believed this caused the symptoms of ME/CFS, which also were the effects of lack of oxygen in different organs.[3]

This article poses the question of whether these non-deformable cells could be the precursors of microclot formation.

And if so, whether Les Simpson’s recommendations for improving blood flow in ME/CFS might be applicable to patients with Long Covid.

https://www.amazon.co.uk/Ramsays-Disease-Encephalomyelitis-Unfortunate-Creation/dp/0957181728

Ramsays Disease – Encephalomyelitis-Unfortunate-Creation

Les Simpson’s Work

Les Simpson PhD, no longer with us, did his research into the haemorheology of ME/CFS during the 80s and 90s, fighting losing battles to have his contributions recognized, while being a hero to the many patients he helped.  A summary of his work and his thinking can be found at [3].  https://www.investinme.org/ArticleJ21-Role-of-Impaired-Capillary-Bloodflow.shtml

Normal functioning of each cell, tissue and organ in our body requires that our red blood cells are able to do their job of delivering oxygen and removing waste products (metabolites) by passing through the micro-circulation, that intricate web of tiny blood vessels (capillaries) that serves every part of our body. 

It has been a given that all red blood cells are biconcave discocytes  [discoid form of red blood cell­], circular, with a dimple on both sides.  As these cells are wider than the smallest capillaries, it is essential that they be able to deform ­ to curl up or stretch out in order to get through these capillaries ­– the microcirculation ­ in order to get to every cell in our body to perform their function of delivering oxygen and removing waste products.  (The fact that blood in our arteries ­ travelling outward ­ is red, and the blood in our veins, returning to our heart is blue, is evidence of this process.)

Les’s work challenged the assumption that all red blood cells had this shape.  He studied immediately fixed samples of blood, and observed six variations on the usual biconcave discocyte shape in a range of chronic conditions, including ME/CFS.  He noted that in these conditions, including both acute and chronic ME/CFS, the proportion of non-discocyte cells in the patient’s blood was increased.  He also noted that that increase varied according to how well or unwell a patient was at the time of taking the sample.

Cells which do not have the biconcave discocyte shape are non-deformable, and cannot get through the smallest capillaries (the microcirculation).  Having an increased proportion of non-deformable red blood cells means that blood flow into the microcirculation will be impeded, and the tissues most sensitive to oxygen deprivation and build-up of waste products (metabolites ­ which produce the “burn” in  overused muscles) will become unable to function normally, potentially causing most or all of the symptoms reported in both ME/CFS and Long Covid.

• Post-exertion fatigue, the failure of muscles to return to pre-exertion functioning, along with worsening of all symptoms, as muscles are forced to go into the anaerobic metabolism, which can only function for a limited time before harm begins to be done;
• Brain fog, when cognitive areas of the brain become oxygen-deprived and suffer a build-up of metabolites;
• Dysregulation of various functions. Likewise, a range of symptoms will arise if cells in the areas of the brain/pituitary which regulate functions such as body temperature, diurnal rhythms, etc. are stressed in the same way.

Thus Les Simpsons observations could easily account for the wide-ranging and otherwise apparently unrelated constellation of symptoms in ME/CFS.

Les Simpson’s Treatment Recommendations

• Six grams of fish oil per day;
• Four grams of genuine EPO per day.  (When this recommendation was queried, he found that of eleven supplements advertised as EPO, only four were genuine);
• Vitamin B12 as Hydroxycobalamin;
• Pentoxifylline.

Each of these seems to have the potential to improve blood flow.  Vitamin B12 injected as Hydroxycobalamin is used for the treatment of pernicious anaemia, and traditionally, as treatment for tiredness.  (Methylcobalamin is the form of Vitamin B12 that the body can use, and it is now available in tablet form)

A research trial of Pentoxifylline for treating blood flow problems in diabetics found that during the four years of the trial, it prevented the need for amputations.

Patient feedback from the ME/CFS groups Les advised during his travels to ME/CFS conferences world-wide during the last decade of the 20th century was that many benefitted from one or another of these suggestions; some did not benefit from any.

Les did not claim to understand the reasons for this.  He did not sell any of these products.  He did not claim that any could provide a cure.

However, with so many reporting benefits, and in the absence of many better options it still  seems worthwhile for ME/CFS  patients to try out these possibilities. Pentoxifylline is the only one not available without prescription. 

Les discusses the basis for his recommendations in the section on Treatment Options[3] but further research is needed.

It is, of course, important to consult your own medical practitioner before experimenting even with widely available supplements.

Contemporary Research

Dr Amy Proal is one of the three founders of the PolyBio Foundation for the study of complex chronic inflammatory conditions.  She is a microbiologist with expertise on the molecular mechanisms by which pathogens modulate human gene expression, metabolism and immunity. She also serves as PolyBio’s Research Team Coordinator.

Her article on microclots in ME/CFS has already been mentioned.[2]

Professor Resia Pretorius is the Head of Department and a Distinguished Research Professor in the Physiological Sciences Department, Faculty of Science, Stellenbosch University, South Africa. She is also the Director of BioCODE Technologies.  Her overall research theme is blood coagulation, circulating inflammatory markers and how these play a role in inflammatory conditions.

 https://youtu.be/C8tzTmVwEpM?t=786

Interview between Dr Proal and Professor Pretorius, Minute 13, when Professor Pretorius
states that as many as 150 symptoms have been reported in Long Covid, and all can be explained by hypoxia ­ lack of oxygen.

In an article by Professor Pretorius et al[4]  the abstract concludes: “Given that blood clots can block micro capillaries and thereby inhibit oxygen exchange, we here investigate if the lingering symptoms that individuals with Long COVID/PASC [Post-Acute Sequelae of COVID-19] manifest might be due to the presence of persistent circulating plasma microclots that are resistant to fibrinolysis.”

In the decades since Les Simpson was doing his research, medical science has made enormous strides in understanding the complexities of viral activity, in the sophisticated technology available to researchers in the laboratory, and in the level of statistical analysis made possible by advances in computer capabilities.

In this context, it may seem simplistic to suggest that research done in the last century could have something important to offer.

But the research on microclots does not appear to take into account the observations that Les Simpson made.  And treatment of microclots seems to rely on anticoagulants, which can be dangerous, and more recently, on HELP anaphoresis [movement of charged particles toward the positive pole (anode) in electrophoresis] (also discussed in the interview above).

HELP anaphoresis is a way of physically sifting microclots out of the blood, by taking it from one arm, passing it through a filtering process, and back into the other arm.  However effective this may prove to be, it clearly is not going to be accessible to more than a tiny proportion of those suffering from Long Covid.

The first question proposed in this article is whether the proliferation of non-deformable erythrocytes observed by Les Simpson, by gathering at sites in the microcirculation which they are no longer able to traverse might be creating the preconditions for the formation of microclots.

The second question is that if this could be the case, might the treatment options described by Simpson be helpful in the treatment of Long Covid?

References

1. Wenjing Chen, Jing Ye Pan Anatomical and Pathological Observation and Analysis of SARS and COVID-19: Microthrombosis Is the Main Cause of Death https://pubmed.ncbi.nlm.nih.gov/33472576/ Jan 2021.
2. Nunes, M and Proal, A et al The occurrence of hyperactivated platelets and fibrinaloid microclots in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) https://www.researchsquare.com/article/rs-1727226/v1 June 2022.
3. Simpson L O PhD The role of impaired capillary blood flow in ME https://www.investinme.org/ArticleJ21-Role-of-Impaired-Capillary-Bloodflow.shtml May 2008.
4. Pretorius et al Persistent Clotting Protein Pathology in Long Covid/Post-Acute Sequelae of COVID-19 (PASC) is Accompanied by Increased Levels of Antiplasmin https://rdcu.be/cPJv9 2021.