Opinion Challenging the current hypothesis that thrombosis is responsible for the post-COVID-19 condition, 2024, Carson, Davey Smith, Garner et al

But doesn't that argument also require that there's no such thing as platelet-poor plasma?

 

Why?
At least some of the bits stuff they showed were much bigger than platelets and would need to be to be of any interest in embolisation.

Isn't platelet poor plasma plasma that has been spun hard enough to get rid of most of the platelets.

Platelet Poor Plasma

1. Centrifuge tube to obtain PPP.
2. Use a plastic transfer pipette to remove plasma (staying away from the buffy coat layer) and transfer top ⅔ of plasma to a plastic aliquot tube.
3. Centrifuge this aliquot tube at 1500 g for 10 minutes.

 

Maybe BSH should be made aware of the extent of it. SBNS intervened when there were unnecessary craniocervical fixation surgeries being carried out in the UK if I recall correctly.

 

I think their argument is naive and simplistic. Thrombosis and embolisation depend both on fibrin polymerisation and platelet aggregation, and can be contributed to by bacterial material as in endocarditis and even immunoglobulin in various forms of thrombotic vasculopathy like visual loss in myeloma.

For sure these are not technically clots and would not be even if they had formed in vivo, but if lumps of anything are floating about in blood anticoagulation might prevent secondary propagation of thrombus. She of the anticoagulants are directed at platelets, so not fibrin meshes per se.

 

They show activated platelets in PPP, which they describe as "spreading" and also "clumping".

So let's say that also allows for "microclot" objects that can be up to the same mass as platelets in the spun-down sample, and maybe up to the same size as activated platelets. Perhaps there could be a partial artefact such that with handling they tend to be more likely to aggregate. This might be similar to the clumping of the platelets. They might appear larger ex vivo than they truly are in circulation.

I think part of the explanation offered is capillary compromise, which might be on the basis of occlusion (ie thromboembolic), but they've also described the "microclots" as inflammatory, which could lead to slower capillary flow due to effects on the blood components, as well as endotheliitis/endothelial dysfunction.

The proteomics data still (to me) suggests that something is genuinely sequestering things like alpha-2-antiplasmin that they highlighted, that only increases with substantial fold-change following the double-digestion trypsinisation of the sample. This was discussed in this recent review presentation.

Regardless of whether the microclots as shown ex vivo are simply artifact, they absolutely could still represent a marker for (novel) pathological hypercoagulability. And their ex vivo size and deformability may relate to symptoms as discussed in May by Martin Kräter.

Resia Pretorius also defends the definition that they are clots earlier in that talk here: "How can you say this is a micro clot?".

You might have to clarify, but that sounds like you're saying anticoagulants are targeting platelets. DAPT (dual anti-platelet therapy, ie aspirin and clopidogrel) target platelets. DOAC (direct oral anticoagulant, eg apixaban or rivoroxiban) are factor Xa inhibitors.

Eg Wikipedia —

 

Maybe that is a different preparation. Their methods are not well described.
But platelet aggregates would be spun out by centrifugation.

Then the aggregation. would be ex vivo - however you try to play it.
Why should they look bigger. I have sent years doing fluorescence microscopy. Things don't suddenly 'look bigger' down a microscope!

But without a scrap of evidence. There is no clinical inflammation and acute phase markers are normal in longCovid. Remember that one of their studies supposedly of LC or ME/CFS (I forget which ) included something like 20% also having rheumatoid. The general methodology was disastrous.

Sorry but this is just stuff they have up. This is my field. There is no such thing as endotheliitis. It has become a popular buzzword for people who never did any formal pathology training (as I did).

I am not denying that they may have hit on some shift in plasma protein levels of interest. What I am staggered by is the entirely ungrounded hyped statements they make all the time about their clot theory and its significance. I am not the only person to think this by any means. The haematologists I have spoken too reagard what I am saying here as obvious. They just think the whole thing is of no great interest.

 

The failure of peer review is scary.

 

Another thing that intrigues me is that Fox and Garner are Liverpool and so is Kell.
Is there some local infighting involved in all this?