No evidence of hypercoagulability, altered fibrinolysis, or increased fibrin(ogen) microaggregates in never‐hospitalized long COVID, 2026, Fraser+

[forestglip]

No evidence of hypercoagulability, altered fibrinolysis, or increased fibrin(ogen) microaggregates in never‐hospitalized long COVID

Spoiler: Authors

Fraser, Emily; Ng, Kher; Hasan, Neda; Dunstan, Isobel; Laws, Avianna; Macrae, Fraser; Abu‐Hanna, Jeries; Ariens, Robert; Harris, Victoria; Oke, Jason; Saunders, Laura; Grist, James; Collier, Guilhem; Hughes, Paul; Wild, Jim; Thompson, Roger; Gleeson, Fergus; Shapiro, Susan

Last paragraph
In summary, in never-hospitalized patients with specialist-confirmed LC, we found no evidence of persistent prothrombotic activation, impaired fibrinolysis, abnormal fibrin fiber architecture or increased fibrin(ogen) microaggregates, and no meaningful associations with breathlessness, fatigue or pulmonary perfusion and gas transfer metrics.

These findings suggest that antithrombotic therapy is not justified outside of clinical trials for never-hospitalized LC or in the absence of a separate recognized indication such as venous or arterial thrombosis.

Web | DOI | PMC | PDF | HemaSphere | Letter | Open Access

 

[Jonathan Edwards]

They used frozen samples. I don't know if others have. Freezing might produce artifactual clumps.

I also note that they centrifuged samples sufficiently to remoce not just red cells but platelets. They only reported on 'aggregates' the size of red cells or bigger,so they must have been formed after centrifugation. This is the whole problem with the 'microclot' story. This group make the cogent point that anythig smaller than red cells (~5microns) would not affect vasculature anyway.

It is interesting that this is published as a letter. I don't see any particular reason for it not to be a formal publication. It is an important negative.

 

[EndME]

Freezing might produce artifactual clumps.

If I remember correctly the Dalton study reported something along those lines.

 

[Hutan]

This looks like a pretty useful study, in terms of suggesting microclots and thrombosis-type events are not a defining feature of LC, and not supporting the use of anti-thrombotic treatments.

I would just note that the team are from Oxford University and the Radcliffe Department of Medicine, which I think has been associated with BPS viewpoints. (Edit: And, of course, the microclot theory has been singled out for BPS criticism.) Also, there were only 37 non-breathless LC and 34 controls (along with 80 Breathless LC), so the sample size wasn't huge, but probably adequate for most of the analyses.

Fibrin fiber and fibrin (ogen) microaggregate analyses were undertaken in 55 samples, randomly selected from within the BLC, NBLC and control groups

The sample size was small for the microaggregate analysis though, with only 55 samples spread across the three groups. The actual participant numbers are only given in a supplementary figure, which is a bit bad. There were 27 Breathless LC, and only 14 Non-breathless LC and 14 controls.

It is interesting that this is published as a letter. I don't see any particular reason for it not to be a formal publication. It is an important negative.

Yes, agreed.

 

[Jonathan Edwards]

The sample size was small for the microaggregate analysis though, with only 55 samples spread across the three groups. The actual participant numbers are only given in a supplementary figure, which is a bit bad. There were 27 Breathless LC, and only 14 Non-breathless LC and 14 controls.

That is actually plenty if microclots are supposed to be important mediators of pathology, as Pretorius and Kell have claimed. I think we forget that when looking for direct disease mediators small groups have to be enough for a difference to be meaningful. If you study calcium in parathyroid adenoma you only need five cases and five controls because they are completely separate ranges.

It is intriguing that in the buspirone study by Sharpe there were 11 controls and 11 cases and the significant difference is plain to see.

In the PRIME symposium Audrey made the comment that we need big cohort studies. We do for the sort of work she is doing, on epidemiology and indirect indicators of cause where there is a small signal to noise ratio but not if we are looking at direct causal agents.