New study finds microclots in ME*; a potential treatment target?

*Previously they were found in Long Covid19.

(Note: This is the second section of my previous post but I felt this study deserved its own article.)

Massimo Nunes, Amy Proal, Etheresia Pretorius and colleagues find fibrinoid microclots in the blood of ME patients.  

So it turns out we did find “something in the blood” of #ME/CFS patients: fibrinoid microclots + hyperactivated platelets (that you can see with your own eyes).

Amy Proal on Twitter. [1]

7/27 Update: this article has now been published [2]; Read the fulltext here.

In preprint–study that looks to be very significant, Massimo Nunes, Amy Proal and colleagues found fibrinoid microclots in the blood of myalgic encephalomyelitis patients [3]–similar to an earlier result finding such clots in Long Covid patients [4].

Using platelet poor plasma Massimo Nunes, Etheresia Pretorius, Amy Proal and colleagues found that when stimulated to clot the plasma from ME patients formed more extensive clotting networks [3]. Also using fluorescence microscopy they found fibrinoid microclots at a burden greater than controls but, interestingly, lesser than acute Covid-19, long Covid-19, and type 2 Diabetes [3]. Using TnT staining they determined these microclots are amyloid in nature and also that “Amyloid protein changes were markedly increased in thrombin-induced fibrin clots.”

The authors suggest these fibrinoid microclots could be both causing blood vessel inflammation (especially in the microvasculature) and serving as a mechanical blocking point to oxygen getting through to microcapillaries [3]. The authors further state it is possible that these fibrinoid microclots could contribute to the pathology in a feed-forward fashion: that the presence of these amyloid microclots leads to inflammation which (by itself or with another factor) leads to more amyloid microclot formation in a repetitive cycle [3]. If this is true, not only would the microclots form a immediate locus for potential treatments but disrupting their formation or removing them more quickly might ameliorate the disease.   

‘To my knowledge, there are only five diseases that have a pathological low sedimentation level: Myalgic Encephalomyelitis, sickle-cell anemia, hereditary spherocytosis, hyper-gammaglobulinemia [and] hyper-fibrogenemia’

Dr. Byron Hyde, quoted in Osler’s Web [5]

The idea that the microcirculation of ME patients could be compromised in some way goes far back. In 1985 a pilot study by Dr. L.O. Simpson found a filtration rate difference between female patients’ blood as compared to healthy controls [6]. In a second study, Simpson found abnormally shaped red blood cells (most especially “cup forms”) in patients which could impair microcirculation [7]. Much more recently, Amit Saha, Ron Davis, and colleagues, found a reduced deformability in red blood cells of patients [8] a finding that is likely related to Simpson’s finding of abnormal erythrocyte forms.

The hypercoagulation hypothesis is also not new: it was first advanced by David Berg in the late 1990s [9]. However, a subsequent follow-up study, by the very reputable ME Research UK group, didn’t find evidence hypercoagulation [10] and thereafter the hypothesis received little attention. This study would have the effect of reviving this hypothesis and providing a plausible mechanism for how it could result in the intolerance to exertion (or visual/auditory/cognitive stimulation) that is one of the core characteristics of the disease. 

If our blood is filled with clotted particules and has a tendency toward hypercoagulation it could also explain the long-mysterious low erythrocyte sedimentation rate found in this disease as most inflammatory diseases have the inverse finding of an elevated sedimentation rate. (Other explanations are also possible: For example, it could be that our red blood cells have a higher negative potential, or that they have altered shapes, or membrane compositions which are resistant to stacking.)

  • One thing important to note is that in this study all patients filled out a questionnaire from the International Consensus Criteria (ICC; the successor criteria to the 2003 Canadian Criteria and the research definition which selects the most severe and uniform group of ME patients).
  • According to this questionnaire the authors found: “Our ME/CFS population therefore constitutes a sub-population suffering the most from post-exertion-related symptoms.”
  • I find it interesting that so much of the research which has consistently found immune or metabolic abnormalities has used the fairly strict Canadian Definition or the ICC and so much research which has not found abnormalities or found them inconsistently has used the old CDC 1994 Definition, or the SEID Definition…

Dr Beate Jaeger and HELP Apheresis

Dr Jaeger was also applying a treatment with which she was already familiar, namely HELP apheresis. This treatment has been used since the 1980s to remove excessive levels of lipid from the blood of patients with coronary artery disease. Dr Jaeger therefore decided that this could be adapted to remove microclots from the circulation of Long Covid patients, by a sophisticated process of filtration. The technique involves continuous removal of blood from one arm vein whence it is filtered, before being returned to the opposite arm.

–Dr. William Weir.

If Nunes, Proal, Pretorius and colleagues are correct and the higher level of microclots in myalgic encephalomyelitis is confirmed and the microclots are not merely an unpleasant side-effect of inflammation but “the thing itself” the question naturally arises: how can they be removed and would their removal effect a clinical improvement?

The following is my synopsis of a summary provided by Dr. William Weir, and shared by Jenny Wilson, of a visit by Weir to Dr. Beate Jaeger at the Mulheim Clinic in Germany.  

Dr Beate Jaeger: Source

Dr. Beate Jaeger is a German doctor who began using HELP Apheresis (a method of separating a harmful constituent in the blood from the rest of the blood that is returned to the patient; HELP is an acronym for : heparin-induced extracorporeal LDL precipitation) to remove microclots from patients with Long-Covid19 and began treating ME patients with this same procedure upon receiving results that they also had increased levels in microclots in the blood. When this material was by a South African team (Dr Pretorius’s group) they found the filtered material was composed of circulating cellular debris, clumps of fibrin, platelets and red blood cells. Dr. Jaeger believes there are also subsets of patients where it is not microclots but lipid globules. The number of procedures needed to completely filter this debris from the blood was 2-10. Clinical improvement in Long-Covid19 was substantial and there was also improvement in the few ME patients treated thus far.

The summary concludes with these encouraging words:

The acid test of Dr Jaeger’s work will be to demonstrate not only subjective symptomatic improvement but also scientifically objective measures of improvement. Sophisticated scanning techniques as well as the recovery of fingerprint patterns will help prove the effectiveness of her treatment. 

I am cautiously optimistic that, when Dr Jaeger’s results appear in the medical literature, HELP apheresis will then be adopted universally as standard treatment for ME/CFS and Long Covid. Time will tell and fingers crossed!

Dr. William Weir

If the finding of microclots and other debris in ME patients’ blood bears out, aside from all else that can be said, such a result of patients having something so visible in their blood would be a stunning rebuke to the doyens of “Institutional Medicine”–especially those in the UK and US governments, who have insisted that the cause of myalgic encephalomyelitis is so ~mysterious~ as to be practically unknowable! So unknowable they felt justified in neglecting to fund its research for these long decades…


  1. Amy Proal. ‘So it turns out we did find “something in the blood.”‘ Retrieved July 12, 2022.
  2. Nunes JM, Kruger A, Proal A, Kell DB, Pretorius E. The Occurrence of Hyperactivated Platelets and Fibrinaloid Microclots in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Pharmaceutical. 2022 July;15(8), 931;
  3. Massimo Nunes, Arneaux Kruger, Amy Proal et al. The occurrence of hyperactivated platelets and fibrinaloid microclots in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 22 June 2022, PREPRINT (Version 2) available at Research Square []
  4. Pretorius E, Vlok M, Venter C, Bezuidenhout JA, Laubscher GJ, Steenkamp J, Kell DB. Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin. Cardiovasc Diabetol. 2021 Aug 23;20(1):172. doi: 10.1186/s12933-021-01359-7. PMID: 34425843; PMCID: PMC8381139.
  5. Johnson, Hillary. Osler’s Web. Crown Publishing, 1996, p. 215.
  6. Simpson LO, Shand BI, Olds RJ. Blood rheology and myalgic encephalomyelitis: a pilot study. Pathology. 1986 Apr;18(2):190-2. doi: 10.3109/00313028609059457. PMID: 3093959.
  7. Simpson LO. Nondiscocytic erythrocytes in myalgic encephalomyelitis. N Z Med J. 1989 Mar 22;102(864):126-7. PMID: 2927808.
  8. Saha AK, Schmidt BR, Wilhelmy J, Nguyen V, Abugherir A, Do JK, Nemat-Gorgani M, Davis RW, Ramasubramanian AK. Red blood cell deformability is diminished in patients with Chronic Fatigue Syndrome. Clin Hemorheol Microcirc. 2019;71(1):113-116. doi: 10.3233/CH-180469. PMID: 30594919; PMCID: PMC6398549.
  9. Berg D, Berg LH, Couvaras J, Harrison H. Chronic fatigue syndrome and/or fibromyalgia as a variation of antiphospholipid antibody syndrome: an explanatory model and approach to laboratory diagnosis. Blood Coagul Fibrinolysis. 1999 Oct;10(7):435-8. doi: 10.1097/00001721-199910000-00006. PMID: 10695770.
  10. Kennedy G, Norris G, Spence V, McLaren M, Belch JJ. Is chronic fatigue syndrome associated with platelet activation? Blood Coagul Fibrinolysis. 2006 Mar;17(2):89-92. doi: 10.1097/01.mbc.0000214705.80997.73. PMID: 16479189.

7 thoughts on “New study finds microclots in ME*; a potential treatment target?

  1. My son Has CFS, so when will trials start?and is further research being done, this is a cruel illness, My son is a qualified psychotherapist, and now is mostly in bed with absolutely no quality of life, financial hardship and marriage break up and this is a familiar story!!!

    1. I’m sorry to hear. It is a very cruel disease and there is so little research. As far as I know Beate Jaeger is the only MD using this therapy currently. You might be able to contact her through her website:

      1. I wouldn’t take aspirin as it could cause other problems. Dairy/gluten free diet helps with B12 shots, folate, ferritin, Vit D and magnesium.

  2. From a lay perspective I am interested (in both senses!) to know whether it is assumed that microclots, if removed, will not reform, or if there is interest and/or possibility to discover why and how they form(ed) with a view to eventually intervening there.

    1. I think you’ve hit on important point: we don’t know whether the microclots are the primary thing messing up our bodies or a secondary effect of something else and we don’t know what is driving their production (aside from whether they are a primary or secondary effect).

      One of the things the authors mentioned is that it was possible the microclots were inducing more microclots in a feedforward loop. The idea being, there are these microclots messing up our microcirculation and the body reacts to that, in susceptible persons, by producing inflammation which leads to more clots. If that was the case, removing the clots should reduce new ones from being formed. Of course it is possible there is no feedforward loop and there is something else which inducing the microclots whether that be infection, autoimmunity or some immune or metabolic derangement.

      Intuitively, the disease feels like something is starving our cells of oxygen, or some other essential metabolic ingredient, and if you look at it this way the microclots being very important would make sense. However, they found a higher area of microclots in type II diabetes and long covid than in myalgic encephalomyelitis–and we know type 2 diabetes does not have the profound systemic debility seen in this disease, which would seem to more support the idea that it is a secondary effect.

  3. There’s two types of findings I get excited by. Deep insights into possible fundamental mechanisms that could be near the top of the chain of causality. And insights that spot something big that might be tracatable (i.e. physically big things you can get at and treat, like bloodclots, as opposed to say, calcium gradients on cell walls!)

    This, to me, falls into the latter category. Which is not to dismiss it. Symptom treatment would be amazing. (A lot of more fundamental research is disappointing for anyone over 30 – it is many years away from having applications!)

    And even if the clots are only symptomatic, – and in fact even if they don’t provide subjective symptomatic relief – watching patients to see in whom they return most quickly could give insights into what is causing them and what *is* in fact upstream.

    1. Jason thanks for the thoughtful comment.

      I think at this point we simply don’t know whether it is a cause or an effect. In my opinion the strongest, though indirect, evidence, that it is an effect is that Proal et al found these microclots in conditions such as type II diabetes which are, at least in the average case, vastly less disabling than myalgic encephalomyelitis. If they are finding these microclots in  several disorders in which inflammation is a component it makes sense to assume it is an effect of inflammation.

      From the other side, Dr. Weir’s letter (“Clinical recovery in virtually all the Long Covid cases was substantial,”) says they are having success treating long-COVID patients with H.E.L.P. Apheresis with whom they started before taking on ME patients. If this truly represents the norm it would seem to make sense to view it as a cause or part of the cause, at least in those cases. 

      One thing I’d diverge a bit from your take is it may be that the final cause, when discovered, isn’t something very arcane but something which immediately makes sense. It’s possible it’s been simply missed due to the lack of manpower. Or it could even have been already discovered but it hasn’t reached the stage of being “popularized” within the field, let alone the larger circle of medicine. One very striking example is a lot of Dr. John Chia’s work on enteroviruses hasn’t been taken up by other researchers to replicate or extend–one cause (imo) is that the field is small so the pool of people who would popularize and extend a discovery is insufficient. I assume similar things have happened with other researchers’ findings. This is a source of frustration to all of us and I am sure it is to them as well… 

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