The micro-clot finding in Long Covid — implications for the possible aetiology of ME/CFS

Indeed, where is the Budd-Chiari liver enlargement or the ventilation perfusion mismatch or reduced GFR?

 

@Jonathan Edwards

Do you know if micro clotting is the result of a persistent infection?

 

Microclotting occurs in subacute bacterial endocarditis. It may occur in other infections but nothing obvious comes to mind immediately.

Remember that what has been reported by Pretorius et al is clotting in a tube rather than clotting in a patient. Clotting occurs in acute severe Covid19 but I have not seen evidence that would go with microblogging in patients in LongCovid. There seems to be an increased risk of some thrombotic events like venous thrombosis of pulmonary embolism but that may just relate to inactivity and generally being unwell.

 

Yes — some conjecture:

What we see is a mixture of anecdotal reports of some people recovering and some not recovering, but from what I've read many do report symptomatic improvement on this combined anticogualant / antiplatelet regimen. I think it's important to note that the combination may be having a positive symptomatic effect, but that people (including on S4ME) report no benefit to long-term ME on a single agent, eg "I was on aspirin or warfarin or rivaroxiban" etc.

I think what this is all pointing to is that the microclotting observation is a downstream effect. It may be genuinely reflecting hypercoagulability, but as Jo says this is clotting in a tube and we don't know if microclots are happening in vivo. It may be a specific feature of LC, or a lesser feature of ME, or present in both but simply something that largely resolves with time even as the underlying ME/LC persists.

I'm running with the idea that "something in the blood" is generated or upregulated — maybe not a lot (so we haven't properly taken notice), but constantly — enough to have major physiological effect over sufficient time. That something has a wide area-of-effect: say the entire vascular lining resulting in endothelial dysfunction; and impairments to some contents of the blood, eg lymphocytes and platelets. That results in many deleterious effects, just one of which might be hypercoagulability which is symptomatically, and maybe also pathogenically, cumulative.

Reducing the hypercoagulability might help with the symptoms, something the patients notice. But it doesn't of itself stop the generation of the something-in-the-blood. That process may simply resolve with time in some, but the treatment regimen is erroneously given credit for this rather than simply some symptomatic relief. (If hypercoagulability somehow also up-regulates the something-in-the-blood as a feed back, then yes it may also be helping).

Aside: I see the team put out a preprint earlier in the week, where they demonstrate the effect via an imaging cytometer. However, I don't think this advances things much or even at all. They again used platelet-poor plasma in citrate tubes, with Thioflavin T and were correlating their prior method with the new one. They suggest that a standard lab (non-imaging) cytometer could also be used as a high throughput assay (counting objects of x-y size), which I presume would be in the absence of ThT. I don't know if that could work with citrated whole blood. They say this is the first attempt to use a cytometer to analyse a non-cell.

I think their idea is that generally flow is impaired rather than blocked blocked? They describe the microclots as resistant to breakdown, but I think also nebulous or at least deformable. Then they would be a bit like a red or white cell that adjusts to fit through the smaller capillaries. Over the capillary network, general vascular flow and flow control might then be degraded (adding to the probably more important NO reduction / endothelial dysfunction).

They always say that the capillaries are blocked, preventing oxygen getting to the tissues - QED. I don't think so simple, although maybe it's contributing. I think the metabolic reprogramming is the primary event — eg the Warburg effect of aerobic glycolysis and reduced fatty acid oxidation etc across many tissues, but perhaps in particular affecting endothelium and lymphocytes.

I haven't looked at liver, but for lungs and kidneys:

Pulmonary Dysfunction after Pediatric COVID-19 (2022, Radiology)

Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-acute COVID-19 Syndrome (2022, Radiology)

Kidney Outcomes in Long COVID (2021, J Soc Am Nephrology) —