Erythrocyte Deformability As a Potential Biomarker for Chronic Fatigue Syndrome, Davis et al (2018)

About eight months after onset, I underwent a battery of tests at a "famous" otologic institute to try to figure out the cause of my continuous "dizziness." They seemed stumped, but a senior doctor there said that they sometimes saw this kind of dizziness with "vascular insufficiency" to the smallest of blood vessels of the inner ear. On their advice, I tried taking niacin to try get my capillaries to dilate, but it produced no improvement. I wonder if it's possible that the problem was not with the diameter of the capillaries, but rather with the rigidity of the RBC's.

I also wonder if this "rigidity" of the RBC's might be the explanation for a 1975 outbreak at a Sacramento, California area hospital (Mercy San Juan) of what was then termed "infectious venulitis." The symptoms were consistent enough with ME that the event is generally included among lists of ME/CFS outbreaks. The odd feature of this outbreak, though, was what seemed to be inflammation of the "venules," the tiny intermediary vessels that lie between the capillaries and the smallest veins. As I recall, some 200 hospital employees were affected as well as a fair number of people outside the hospital. I've seen photos of patients in this outbreak with what appear to be ugly bruises. A doctor who observed this outbreak wrote an interesting summary of it here: https://me-pedia.org/images/6/6e/Erich_Ryll_Infectious_Venulitis.pdf

[ETA: This article is actually a more thorough account of the Sacramento outbreak written by the same physician. Includes photos: http://iacfsme.org/portals/0/pdf/Summer2011-Ryll-30YearReview-2-46.pdf ]

If it's severe enough, could impaired RBC deformity actually wind up damaging the smallest of blood vessels that they traverse?

[ESR's down to zero are considered in "normal" range, although low values are associated with some conditions, like sickle cell anemia. FWIW, about a month after onset, my ESR was measured as "3." I think this is the only time it was ever measured.]

 

I do regard this as a biomarker, just not a diagnostic biomarker. It might also be used as an outcome biomarker for assessing treatments.

It still requires a large cohort for replication, including milder severities.

 

Not a top journal after all

https://twitter.com/user/status/1067567986897170432

 

Back in the 60s I worked as a lab tech, and used to do ESRs. (Using the Westergren method, I have no experience of Wintrobe though I seem to remember they used that at the children's hospital) There's an article on how to do it here. And a bit about clinical significance too.

If you look at the tubes used you can see that the difference between 0 and 5 is really pretty small, at the lower end it isn't really possible to measure meaningfully for comparison with only small differences. I would think that it might be within allowable lab error.

ESR is much more useful for measuring larger differences over time, or to look for a single high reading that prob indicates inflammation. It's a general test of "there's something happening" IYSWIM.

 

I'll be interested to read the full paper when it's available (or perhaps if it's available - if this is an abstract of what will be presented at their conference then this may be all that is published for now). For now - like so much recent ME/CFS research - it's in the promising-but-needs-replication-and-testing-on-other-illnesses-and-sedentary-controls category. Pleased to see OMF work getting down on paper though.

Re Mark Guthridge's comments, it is true that this appears to contradict the Australian result (Immune and hemorheological changes in Chronic Fatigue Syndrome) but it certainly looks like the method of testing deformability was significantly different, which may well explain this. As I say, I would love to read a full paper on this, in the hope that the discussion section would cover whether there is strong evidence that the result is due to oxidative stress, as discussed in the abstract, rather than being potentially caused by deconditioning; although I imagine deconditioning, in itself, may cause some level of oxidative stress.

 

@alex3619 why do u not see it as a potential diagnostic biomarker?

 

Because while it will have a high sensitivity, it will most likely have a very low specificity, or an inability to distinguish ME from many other diseases. So it can be used as a support test, but not a primary diagnostic test.

It might also be diagnostic in combination with other tests. Combinations of tests need their own specific studies.

 

Separating out Ron's quote for easier reading

He certainly seems confident in the results.

 

There seems to be alot of devices in the making.

 

From Linda Tannenbaum

So it seems it is published in Blood Journal..

 

I must admit I am confused about where it is exactly published and what kind of publication it is. But aside from that it is rather pleasing I must say to see the team publish.

Not that I understand how important this might be, or whether it is unique to ME/CFS. But I understand much larger cohorts are necessary that include comparisons with e.g. sedentary, healthy and other neurological perhaps disease controls.

And I am a bit worried that we need new technology that has yet to be invented to test for a possible biomarker. I think when we have to sell something like this to 'the established medical world' it will be that much harder.

But I'm looking forward to trying to read the full paper and hearing from others who are far more capable than me what it's really all about!

 

well you took the words out of my mouth there @Russell Fleming

I must say i am missing @Jonathan Edwards' input on these things. (assuming i understand why he's not around but i still miss his input )

 

Even Ron has said that the early testing needs to be improved. I might be mis-remembering, but I think Ron said the first instrument used five nanometer tubules, they want to re-manufacture to 3 nanometers. The reason is that there is some overlap between patients and controls, but at smaller diameters this overlap will hopefully disappear. If so then expect yet another paper next year or something.

The non-specificity to ME is the biggest hurdle though, just as will many of our tests, including the 2 day CPET. Its not that we know of other diseases these findings are found in, though we do for blood cell deformity, its that we have to reasonably prove that.

 

This is indeed one of the issues.

 

When you click on the 'table of contents' for the article it takes you to this collection of abstracts from a conference: http://www.bloodjournal.org/content/132/Suppl_1

That's quite different to a normal issue of the journal, eg: http://www.bloodjournal.org/content/132/21?current-issue=y

I don't know what exactly that means for bragging rights over journal prestige. For results like this it doesn't really matter where something is published so long as the results hold up under independent replication imo. If this is a non-peer reviewed conference abstract of no real standing, but leads on to a solid test for identifying problems of many of those with CFS then that would be more than enough!

 

Someone posted on Phoenix Rising that the paper has been accepted for publication but is not yet online.

 

Perfectly put. I am concerned about this claim: it would explain how they get such a small P value from the tiny sample, but that P value does not tell you how likely the finding is to hold up in the wider patient population. On the letter is what we need to know.

There is another issue. IIRC, statistical theory says that you need a sample of at least 20 patients per group to have confidence that the sample is representative of the wider population (which is why you see very few studies published with fewer than 20 individuals per group).