OMFScienceWednesdays-red blood cell deformability in ME/CFS

[Ben H]

Hi guys,

On this #OMFScienceWednesday, we present a new project that we are funding that will evaluate the ‘deformability’ of red blood cells as a potential biomarker for ME/CFS. Red blood cells (RBCs) are the most common cells in the blood. Their main role is to transport oxygen and carbon dioxide in the blood, and this role depends in part on their ‘deformability’ / elasticity as they flow through small blood vessels.

Alterations in RBC deformability have been associated with inflammation and diseases like sepsis, and some studies suggest that RBC damage occurs in ME/CFS. These observations along with new technology available for measuring RBC deformability prompted Dr. Ron Davis’ team at Stanford and their collaborators at San Jose State University to examine RBC deformability in ME/CFS.

In some very early data generated by this team, there are indications that RBC deformability is reduced in some ME/CFS patients. The ME/CFS RBCs tested so far seem to move more slowly and elongate less than healthy controls, according to tests with this new technology. We are funding a project to confirm these findings in additional patients, and to study RBCs using additional methods, including various types of advanced microscopy, to better understand why these differences exist.

If these experiments are successful, they may establish a new biomarker for ME/CFS that could assist in diagnosis and possibly finding new treatments! Stay tuned for more.

Learn more about RBCs in this Khan Academy video:

B

 

[AdamS]

Cheers for the update Ben, sounds intruiguing, i’m excited to hear more about this!

 

[Sushi]

The ME/CFS RBCs tested so far seem to move more slowly and elongate less than healthy controls, according to tests with this new technology.

Could this be related to the finding mentioned earlier of "thick blood?" @Janet Dafoe (Rose49)

 

[shannah]

Is any expected completion date available @Ben H ?

 

[Murph]

This is super exciting. Blood cells that don't deform properly could be very relevant.

I recently learned that one reason blood vessels relax is because when red blood cells go through tight points in the blood vessels, the red blood cells get squished and bumped, which causes them to release ATP, which acts as a vasodilatory signal. If the red blood cells don't squeeze when they go through tight points, becuas they are stiff, you won't get the vasodilation you need.

(Another cause of vasodilation is that when vessels are too narrow for the amount of blood going through, the vessels get bumped and pushed by the blood cells. This is called shear stress. In response, they are supposed to relax, which they do by releasing Nitric oxide (NO). You will remember that Fluge and Mella patented an NO supplement for ME/CFS.)

POTS is also related to problems with vasodilation and vasoconstriction, so there's clear evidence a lot of us have problems there.

Vasodilation (blood vessels getting wider) is crucial for getting enough blood (and the oxygen it carries) to muscles which are working. Without sufficient blood flow, you could get tired very quickly, and maybe end up doing anaerobic respiration, causing lactic acid buildup. [hopefully this all sounds like it's fitting together!]

Here's a good except of a paper from 2013

Controlled release of ATP from red blood cells (RBC) in response to mechanical deformation or hemoglobin desaturation is a key physiological process for matching oxygen supply with demand in both pulmonary and systemic tissues[8]. Released ATP binds to endothelial purinergic receptors and initiates signaling events that ultimately lead to increased vasodilator and/or decreased vasoconstrictor activity[9]; the net effect being increased blood flow.

Seminal studies over the last decade have mapped out elements of the signaling pathway in RBC that regulates ATP release and involves Gi-proteins, cAMP activation of PKA and key roles for CFTR and Pannexin proteins[8] and have done much to dispel the notion that RBC are ‘dead’ cellular bags whose sole function is to compartmentalize hemoglobin. Furthermore, dysfunction in this signaling pathway has been demonstrated in diabetic and pulmonary hypertensive patients with the concomitant loss of ATP dependent regulation of blood flow discussed as a possible mechanism underlying vascular complications that characterize these diseases​

Incidentally, it's interesting this mentions purinergic signalling, which is Robert Naviaux's pet theory. However it seems like a specific case, rater than the generic case (sickness behaviour/winter metabolism) that Naviaux is pursuing. Open to hearing if anyone can see a linkage there.

My personal case history suggests to me problems with vasodilation, because the things I can't stand are all things that would normally cause vasodilation - exercise, alcohol, warm weather, mental stress - and especially all of these at once. I also seem to do better with high iron supplementation. So I'm pretty interested in this hypothesis.

 

[Gemini]

Hi guys,

On this #OMFScienceWednesday, we present a new project that we are funding that will evaluate the ‘deformability’ of red blood cells as a potential biomarker for ME/CFS. Red blood cells (RBCs) are the most common cells in the blood. Their main role is to transport oxygen and carbon dioxide in the blood, and this role depends in part on their ‘deformability’ / elasticity as they flow through small blood vessels.

A recent discussion of misshapen Red blood cells in ME/CFS and Simpson's research is on this thread:

http://forums.phoenixrising.me/inde...prof-ron-davis-video.56737/page-6#post-959242

 

[Gingergrrl]

POTS is also related to problems with vasodilation and vasoconstriction, so there's clear evidence a lot of us have problems there.

I agree that there seems to be a connection or a subgroup in which this is a major issue.

My personal case history suggests to me problems with vasodilation, because the things I can't stand are all things that would normally cause vasodilation - exercise, alcohol, warm weather, mental stress - and especially all of these at once.

I also am intolerant of exercise, alcohol, hot weather (and mental stress definitely can affect my POTS and Dysautonomia as well).

I also seem to do better with high iron supplementation.

@Murph, do you also test anemic (or borderline anemic) and very low B-12 on blood tests unless you supplement?

 

[Nickster]

Interesting because my son had a nerve biopsy and pathology indicated a vasculitis of the small blood vessels. His red blood cell count has been very low due to other health issues and his me/cfs symptoms have improved. Also, when he was in the hospital they kept thinking he had a sepsis condition. This all could be a big clue.

 

[Nickster]

Another thing with Nick is that his red blood cell count lowered and his liver started to make red blood cells instead of his bone marrow which is the natural way to get red blood cells. Ucla hospital did some further testing to find out why the liver kicked in to produce the red blood cells.

 

[Murph]

Another thing with Nick is that his red blood cell count lowered and his liver started to make red blood cells instead of his bone marrow which is the natural way to get red blood cells. Ucla hospital did some further testing to find out why the liver kicked in to produce the red blood cells.

Would be very interesting to see if UCLA would test for red blood cell deformability...

 

[Murph]

I h

@Murph, do you also test anemic (or borderline anemic) and very low B-12 on blood tests unless you supplement?

I've tested low for iron in the past. Haven't tested for a while but this reminds me I should.

 

[jimells]

the red blood cells get squished and bumped, which causes them to release ATP,

and extracellular ATP can activate mast cells. Additionally, those of us with hyperadrenergic POTS have increased norepinephrine, which causes vasoconstriction in the brain, gut, kidneys, hands and feet, etc.

Norepinephrine is one of the 200 mast cell mediators. So we are looking at a very destructive feedback loop: red blood cells release extracellular ATP ->
extracellular ATP activates mast cells ->
mast cells release norepinephrine ->
norepinephrine causes vasoconstriction in brain, etc. ->
red blood cells release even more extracellular ATP

This is a cycle that has sent me to the emergency room a few times. The last time this happened, it seemed to have been triggered by a newly-acquired peanut allergy. The ER doctor's diagnosis was dehydration, panic attack, obsessive-compulsive, etc.

For me, sometimes IV saline stops this cycle - could the extra fluid enlarge blood vessels, like filling a balloon with water?

Mast cells can also have detrimental effects on red blood cells. See Afrin's Mastocytosis lecture here. He describes a case study of polycythemia – too many red blood cells, and another case study of
pure red cell aplasia - too few red blood cells.

I sure hope that researchers start looking at the role of mast cells in ME someday soon.

 

[Janet Dafoe]

I'm sending all these comments to Ron. You guys know so much!

 

[Murph]

I have to drink absurd quantities of water to feel normal. I also take potassium and magnesium. Here's some 1988 research on red blood cell deformability: (It basically says hydration is important for deformability, and so is potassium.)

I wonder if hydration could play a role in our deformability issues, and this "thick blood" that was mentioned recently by Ron.

Hydration is also a major treatment for POTS.

 

[shannah]

Here's some 1988 research on red blood cell deformability:

View attachment 26553

I wonder if hydration could play a role in deformability, and this "thick blood" that was mentioned recently by Ron.

The Lyme community talks about 'thick blood' all the time. Some feel serrapeptase, natokinase and other enzymes help, none of which did anything for me - except further deplete the finances.

 

[Legolas]

Keep in mind that fast filling with iv fluids like Na Cl 0.9% causes hemodilution and gets your hematocrit more towards 30%. The optimal oxygen delivery of blood is achieved with a hematocrit of around 30%, because you have a good balance between rheology (viscosity; the lower the Hct, the better) and oxygen carrying capacity. So with a hematocrite of 30% blood delivers O2 the best in resting state.

ODI; oxygen delivery index
SBV: systolic blood viscosity

 

[Hip]

Here is a page briefly detaining Dr Leslie Simpson's research on red blood cell shape in ME/CFS.

Healthy people usually have a higher percentage of the disc shaped blood cells, which flow easier than the other shapes. In his studies, Dr Simpson found ME/CFS patients tend to have a higher percentage of cup-shaped and other shaped blood cells which have more difficulty getting through small capillaries.



This page details Dr David Berg's research into blood hypercoagulation in ME/CFS.

Dr Berg and others found that in ME/CFS, there is a small but constant production of thrombin being released into the blood. Thrombin results in the production of soluble fibrin monomer (SFM), a sticky protein that increases blood viscosity.

 

[Nickster]

My son was put on blood thinners. I wonder how this changes the shape of the blood. Does anyone else take blood thinners?

 

[Sushi]

This page details Dr David Berg's research into blood hypercoagulation in ME/CFS.

Dr Berg and others found that in ME/CFS, there is a small but constant production of the the thrombin being released into the blood. Thrombin results in the production of soluble fibrin monomer (SFM), a sticky protein that increases blood viscosity.

I took the ISAC panel developed by Dr. Berg and did have "thick blood." I took injected heparin for a few months and did notice and uptick in functionality.

My son was put on blood thinners. I wonder how this changes the shape of the blood. Does anyone else take blood thinners?

What one does Nick take? There are several kinds with different mechanisms and not sure which type would target the type of "thick blood" that Dr. Davis observed. I take Eliquis, an anticoagulant (for a different reason), and have wondered if it affects the condition Dr. Davis noticed. Anyone know what type of blood thinner might be effective here? Of course we would need to know more about the composition of the blood Dr. Davis was working with. @Butydoc

 

[alex3619]

Blood thinners put me in whole body burning pain, though worse in skin, at least for Clexane. My iron is always lowish but normal (10), despite being an haemochromatosis carrier and eating red meat. Essential fatty acid issues, including oxidation of membrane fats, might also cause cell deformation. I had this discussion with Simpson a bit less than 20 years ago. Its important to not just note the problem, and find associations with symptoms, but to identify the underlying biochemistry.