Combined triple treatment of fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ PACS..., 2021, Pretorius et al

Combined triple treatment of fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) can resolve their persistent symptoms

Etheresia Pretorius, Chantelle Venter, Gert Laubshder, Maritha Kotze, Kelebogile Moremi, Sunday Oladejo, Liam Watson, Kanshu Rajaratnam, Douglas Kell


Abstract:
We recognise that fibrin(ogen) amyloid microclots and platelet hyperactivation, that we have previously observed in COVID-19 and Long COVID/Post-Acute Sequelae of COVID-19 (PASC) patients, might form a suitable set of foci for the clinical treatment of the symptoms of long COVID/PASC.

We first report on the comorbidities and symptoms found in a cohort of 845 South African Long COVID/PASC patients who filled in the South African Long COVID/PASC registry, of which hypertension and high cholesterol levels (dyslipidaemia) were the most important comorbidities.

The gender balance (70% female) and the most commonly reported Long COVID/PASC symptoms (fatigue, brain fog, loss of concentration and forgetfulness, shortness of breath, as well as joint and muscle pains) were comparable to those reported elsewhere. This suggests that our sample was not at all atypical.

Using a previously published scoring system for fibrin amyloid microclots and platelet pathology, we analysed blood samples from 70 patients, and report the presence of significant fibrin amyloid microclots and platelet pathology in all cases; these were associated with Long COVID/PASC symptoms that persisted after the recovery from acute COVID-19. A subset of 24 patients was treated with one month of dual antiplatelet therapy (DAPT) (Clopidogrel 75mg/Aspirin 75mg) once a day, as well as a direct oral anticoagulant (DOAC) (Apixiban) 5 mg twice a day. A proton pump inhibitor (PPI) pantoprazole 40 mg/day was also prescribed for gastric protection. Such a regime must only be followed under strict and qualified medical guidance to obviate any dangers, especially haemorrhagic bleeding, and of the therapy as a whole. Thromboelastography (TEG®) was used to assist in determining their clotting status.

Each of the 24 treated cases reported that their main symptoms were resolved and fatigue as the main symptom was relieved, and this was also reflected in a decrease of both the fibrin amyloid microclots and platelet pathology scores. Nine patients were genotyped for genetic variation in homocysteine metabolism implicated in hypertension, a common COVID-19 co-morbidity reported in both patients found to be homozygous for the risk-associated MTHFR 677 T-allele. Fibrin amyloid microclots that block capillaries and inhibit the transport of O2 to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC.

The removal and reversal of these underlying epitheliopathies underlying this provide an important treatment option that seems to be highly efficacious, and warrants controlled clinical studies.

https://www.researchsquare.com/article/rs-1205453/v1?s=09

 

Just to help with future searching: minor point for thread title and tagging - it's 'PASC' not 'PACS'.
(PACS is 'Picture Archiving and Communication System' i.e. computerised medical imaging systems).

 

This is a version of long-covid that seems a long way off from what we call me/cfs

I have to say I'm confused by the lattice network, it's not intuitive just looking at the chart, so I'll just refer to the statement.

Hence why I'm hesitant to celebrate the influx of a long-covid research as a boon to me/cfs research. No mention of PEM.

Then they selected for patients that looked like they might have clotting symptoms (24 of the original 70), then they did a placebo-less, unblinded treatment, at maybe a self-selective clinic with their own clotting and microclotting ranking system. Seems like a mess it's beyond me to interpret.

 

I hadn't realized just how problematic this paper was. It looks like the finding of 'micro-clotting' is not even exclusive to long covid, but a result of trawling in various diseases, like diabetes, parkinsons and dementia.

The results section doesn't make it clear but I believe their is no record of scoring for the 70 patients that it is claimed all had a visible pathology. However, we have the scoring before and after treatment for the treated 24 patients. The results are on page 13.

Clumping score (I believe out of 8) 4.4 to 3.6

Micro clot Score (I believe out of 4) 2.7 to 1.7

and (total out of 12) 7 to 5.2.

Again, this is unvalidated scoring anyway. I have also noticed the COI, from reading the microclot thread via @CRG , and is indeed worrying.

So, the COI is not irrelevant, accruing microclot findings via a sort of subjective method, increases the value to the SAA detection test.

 

All the points made above are well taken. But just the same, the ideas piqued my interest.

I have consistently high platelet counts, which I was told (and have since read) are a marker of ongoing inflammation. I am tested for SAA every couple of years, and sometimes it is just above the safe level. Ditto for ESR ad CRP, these are sometimes elevated, sometimes not. The platelet count is the most stable of the four markers, it stays consistently high, while the others dance about all over the place.

My background is: diagnosed with CFS in the 1990s, but in 2018, I was given a tentative diagnosis of an autoinflammatory disorder called PFAPA. Mainly on the basis of the inflammatory tetrad described above, and also my (very extreme) inflammatory response to a vaccine challenge, positive response to prednisone, recurrent low grade fevers and tachycardia.

So for me, the idea that platelets might play some role in fatigue is an interesting one.

Anyone else got high platelet counts?

 

It's the opposite for me. Platelets very consistently tending low, squeaking in only just to inside the normal range. Weirdly I still have 'sticky' blood to the point that sometimes the nurse literally pulls clots from my veins when removing a clogged up needle. It looks a bit like strings of mozzarella pulling away from a pizza except it's dark red.
Sorry if anyone was actually eating while reading this

As for a link with fatigue, I'm one of those without constant fatigue, for me it's more a relapsing thing. I'm extremely easily fatiguable but when on top of my pacing I don't have fatigue. Sure, it only takes a couple of minutes of standing up to bring it back on but if I can stay reclined with enough periods resting lying completely flat - no fatigue.

I would have thought that if 'sticky' blood, whether because of clots, platelets or some other reason, was causing fatigue it would be a more constant fatigue, not the wild swings from no fatigue at all when well rested to completely wiped out in PEM. Of course some pwME do report just such constant, unrelenting fatigue.

I've no idea what to make of any of this

 

Yes, I see your point. I'm not in constant fatigue either, only during what I call "flares" (sometimes they follow overexertion, sometimes they happen for no apparent reason at all). So yes, you're right, it couldn't be the platelets without some very heavy theory-massaging.

 

It is fascinating to read about the MTHFR gene mutation discussed, that specific gene mutation is indeed associated with clotting problem and cardio-vascular issues. It really jumped out for me because MTHFR gene mutations has been discussed so much a few years back. Perhaps those carrying the mutation (20-30% of healthy population) would be more at risk after contracting COVID?

 

Moved post

Interesting thread on thrombosis, how platelets working with neutrophils make an important part of the innate immune system, how more likely it is that there is a source for those microthromboses and microclots, which would make treatment like IVIG and apheresis unlikely to succeed (and would be a disaster anyway, as it would be impossible to make those treatments available at the scale they are needed, a similar problem that the PACE model faced even if it worked, but that didn't bother them since they knew it would never be deployed this way).

https://twitter.com/user/status/1515143282636247041

 

Note that this has been resubmitted (now version 2) as a pre-print/not yet peer-reviewed. The title has been changed to —

Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC)

The focus of the paper has changed and so probably warrants a new thread, however that might best wait until the paper is actually accepted.

Abstract
Background: Fibrin(ogen) amyloid microclots and platelet hyperactivation previously reported as a novel finding in South African patients with the coronavirus 2019 disease (COVID-19) and Long COVID/Post-Acute Sequelae of COVID-19 (PASC), might form a suitable set of foci for the clinical treatment of the symptoms of long COVID/PASC. A Long COVID/PASC Registry was subsequently established as an online platform where patients can report Long COVID/PASC symptoms and previous comorbidities.

Methods: In this study, we report on the comorbidities and persistent symptoms, using data obtained from 845 South African Long COVID/PASC patients. By using a previously published scoring system for fibrin amyloid microclots and platelet pathology, we also analysed blood samples from 80 patients, and report the presence of significant fibrin amyloid microclots and platelet pathology in all cases.

Results: Hypertension, high cholesterol levels (dyslipidaemia), cardiovascular disease and type 2 diabetes mellitus (T2DM) were found to be the most important comorbidities. The gender balance (70% female) and the most commonly reported Long COVID/PASC symptoms (fatigue, brain fog, loss of concentration and forgetfulness, shortness of breath, as well as joint and muscle pains) were comparable to those reported elsewhere. These findings confirmed that our sample was not atypical. Microclot and platelet pathologies were associated with Long COVID/PASC symptoms that persisted after the recovery from acute COVID-19.

Conclusions: Fibrin amyloid microclots that block capillaries and inhibit the transport of O2 to tissues, accompanied by platelet hyperactivation, provide a ready explanation for the symptoms of Long COVID/PASC. Removal and reversal of these underlying endotheliopathies provide an important treatment option that urgently warrants controlled clinical studies to determine efficacy in patients with a diversity of comorbidities impacting on SARS-CoV-2 infection and COVID-19 severity. We suggest that our platelet and clotting grading system provides a simple and cost-effective diagnostic method for early detection of long COVID/PASC as a major determinant of effective treatment regimens, including those focusing on reducing clot burden and platelet hyperactivation.

 

Mine are low too. I just had some labs done and I'm somewhat under the reference values.

 

I’m low on platelets,maybe being activated is using them up

 

So now that everyone is checking their platelet count : Mine is very consistently right in the middle of perfect. I do have severe fatigue as part of my symptoms.

 

How would one check/know? I have some blood test results saved but I don't know what all the names are!

 

Ha! Fair enough I'll look for that!

 

+1 to above