Treatment of Long COVID symptoms with triple anticoagulant therapy (Laubscher, Pretorious et al, 2023)

[Murph]

https://www.researchsquare.com/article/rs-2697680/v1

Treatment of Long COVID symptoms with triple anticoagulant therapy


https://doi.org/10.21203/rs.3.rs-2697680/v1
This work is licensed under a CC BY 4.0 License

Background: Fibrin(ogen) amyloid microclots and platelet hyperactivation are key pathological findings in patients with acute COVID-19 infection and also in those with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). These pathologies may represent a suitable target for pharmacological treatment of Long COVID.

Methods: Here we report on the symptoms displayed by a cohort of 91 South African Long COVID patients at baseline and after a clinician-initiated anticoagulant regime was completed. For laboratory analysis, patients provided a blood sample before and after treatment. Fibrinaloid microclot presence was studied by adding thioflavin T to platelet poor plasma (PPP), whilst platelet hyperactivation was studied using two platelet markers- PAC1 and CD62P (P-selectin). The anticoagulant regime included dual antiplatelet therapy (DAPT- Clopidogrel 75mg + Aspirin 75mg) once a day, and a direct oral anticoagulant (DOAC- Apixaban) 5mg twice a day. A proton pump inhibitor (PPI) pantoprazole 40 mg/day was also prescribed for gastric protection. Each of the treated cases reported their main Long COVID symptoms, and whether their symptoms resolved following treatment or not.

Results: In our cohort a most participants did not report any comorbidities before acute COVID-19 infection. Hypertension and dyslipidaemia were the commonest underlying illnesses, whilst the most commonly reported Long COVID symptoms included fatigue, cognitive dysfunction, shortness of breath, and joint and muscle pains. Following completion of treatment, each of the different symptoms resolved in the majority of patients. This was also reflected in the laboratory analysis, where a decrease in the severity of fibrin amyloid microclotting and the degree of platelet pathology was noted. No serious adverse bleeding events were reported.

Conclusions: Fibrin amyloid microclots, platelet hyperactivation/ aggregation, and widespread endothelialitis inhibit the transport of oxygen at a capillary/cellular level. This provides a ready explanation for the symptoms of Long COVID. By normalizing the failed clotting physiology and reversal of the endothelialitis, triple anticoagulant therapy represents a promising treatment option that appears to be highly efficacious, and warrants controlled clinical studies. We caution that such a regime must only be followed under expert medical supervision in view of the risk of bleeding.

 

[Murph]

This publication is from the famous microclots researcher Resia Pretorious. It looks pretty hopeful. They collect survey data that shows 80% of the patients feel a lot better, and at the same time they look at the microclots: in patients who improved, it looks like the below:

It's just a case series of the initial patients they've tried to treat so there's no control group but it all looks quite promising.

 

[BrightCandle]

It's underpowered unfortunately. The lack of control really hampers this making progress for what doctors will perceive as a very dangerous protocol especially when they can't validate if their patient has microclots yet. I am disappointed in how they chose to do this and the lack of blinding is also really a concern. The only way this makes progress is someone does a blinded RCT and iIam not sure who would given the special equipment for the microclots. Not coming to a GP near you anytime soon.

 

[SWAlexander]

 

[SWAlexander]

A friend (in research) comments on: "Treatment of Long COVID symptoms with triple anticoagulant therapy (Laubscher, Pretorious et al, 2023)"
"...now we all can go back to retirement."
"...long haulers will be saved"

 

[BrightCandle]

I was thinking today beyond just the study being underpowered in basic method that actually this is sort of a negative result for microclots. generally We have a bunch of people that have to be on triple therapy, potentially for years and they gain some improvement from it but you remove the therapy and they get worse. That right there suggests that microclots is not the core pathology (and I think these researchers thought it might be) and more to the point addressing does not break the body out of a held state. So to some extent this study actually shows us something quite important, its a negative for clots maintaining the condition and for treating them treating core pathology.

So microclots must be downstream of the real effect, its a symptom its not the cause. This makes them a problematic biomarker since they don't correlate well with severity especially when mostly removed.

 

[SWAlexander]

That right there suggests that microclots is not the core pathology

This makes them a problematic biomarker since they don't correlate well with severity especially when mostly removed.

I agree. Microclots are just one piece of a giant puzzle.
For this reason, I would not call BC 007 the miracle that cures CFS. BC 007 improves blood flow by dilating blood vessels, just another kind of blood thinner.

 

[hopefulalligator]

I was thinking today beyond just the study being underpowered in basic method that actually this is sort of a negative result for microclots. generally We have a bunch of people that have to be on triple therapy, potentially for years and they gain some improvement from it but you remove the therapy and they get worse. That right there suggests that microclots is not the core pathology (and I think these researchers thought it might be) and more to the point addressing does not break the body out of a held state. So to some extent this study actually shows us something quite important, its a negative for clots maintaining the condition and for treating them treating core pathology.

So microclots must be downstream of the real effect, its a symptom its not the cause. This makes them a problematic biomarker since they don't correlate well with severity especially when mostly removed.

@BrightCandle what do you mean "generally we have a bunch of people that have to be on triple therapy, potentially for years and they gain some improvement from it but you remove the therapy and they get worse"- are you saying that we've seen folks on this same protocol need to stay on it for the long term, and when they come off it they get worse? Do you mean long covid folks or me/cfs folks pre-long covid?

 

[Husband of]

I was thinking today beyond just the study being underpowered in basic method that actually this is sort of a negative result for microclots. generally We have a bunch of people that have to be on triple therapy, potentially for years and they gain some improvement from it but you remove the therapy and they get worse. That right there suggests that microclots is not the core pathology (and I think these researchers thought it might be) and more to the point addressing does not break the body out of a held state. So to some extent this study actually shows us something quite important, its a negative for clots maintaining the condition and for treating them treating core pathology.

So microclots must be downstream of the real effect, its a symptom its not the cause. This makes them a problematic biomarker since they don't correlate well with severity especially when mostly removed.

They don't think microclots are the cause. They think damage to the endothelium is the cause. And they think over time the endothelium can heal if you keep up the micro lot treatments. But they note that stresses to the system will result in setbacks.

Laubscher says 5 out of the 375 patients he has treated have failed to respond at all. And two have had severe bleeding issues.

He also says the earlier you treat the less time it takes for improvement, but he has people that have had long COVID for two years who have responded, it just took months rather than weeks

 

[Violeta]

Ken Lassesen has been talking about thick blood/microclots in ME/CFS for ages.

Look at all the information about choices to deal with it he provides.

https://cfsremission.com/2015/09/08/thick-blood-supplements-for-cfs/

 

[Violeta]

Have you seen the information about hyperactivated platelets?

Way over my head, but: "According to the study findings, aberrant platelet aggregation and cardiovascular complications observed in COVID-19 patients are primarily mediated via tyrosine kinase Syk-induced immunoreceptor signaling as well as C5a/C5aR complement pathway signaling.

https://twitter.com/i/web/status/1590112875569635328