A Perspective on How Fibrinaloid Microclots and Platelet Pathology May be Applied in Clinical Investigations DOI Creative Commons
Etheresia Pretorius, Douglas B. Kell

Seminars in Thrombosis and Hemostasis, Journal Year: 2023, Volume and Issue: 50(04), P. 537 - 551

Published: Sept. 25, 2023

Abstract Microscopy imaging has enabled us to establish the presence of fibrin(ogen) amyloid (fibrinaloid) microclots in a range chronic, inflammatory diseases. Microclots may also be induced by variety purified substances, often at very low concentrations. These molecules include bacterial inflammagens, serum A, and S1 spike protein severe acute respiratory syndrome coronavirus 2. Here, we explore which properties these might used contribute differential clinical diagnoses prognoses various diseases with they associated. Such distributions their size number before after addition exogenous thrombin, spectral properties, diameter fibers are made, resistance proteolysis proteases, cross-seeding ability, concentration dependence ability bind small including fluorogenic stains. Measuring microclot parameters, together microscopy itself, along methodologies like proteomics flow cytometry, as well more conventional assays such those for cytokines, open up possibility much finer use generative methods future where personalized medicine will standard procedures all clotting pathology disease diagnoses.

Language: Английский

Possible Role of Fibrinaloid Microclots in Postural Orthostatic Tachycardia Syndrome (POTS): Focus on Long COVID DOI Open Access
Douglas B. Kell, Asad Khan,

Binita Kane

et al.

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(2), P. 170 - 170

Published: Jan. 31, 2024

Postural orthostatic tachycardia syndrome (POTS) is a common accompaniment of variety chronic, inflammatory diseases, including long COVID, as are small, insoluble, 'fibrinaloid' microclots. We here develop the argument, with accompanying evidence, that fibrinaloid microclots, through their ability to block flow blood microcapillaries and thus cause tissue hypoxia, not simply correlated but in fact, by preceding it, may be chief intermediary POTS, which body's exaggerated 'physiological' response hypoxia. Similar reasoning accounts for symptoms bundled under term 'fatigue'. Amyloids known membrane disruptors, when targets nerve membranes, this can explain neurotoxicity hence autonomic nervous system dysfunction contributes POTS. Taken together view, we indicate microclots serve link POTS fatigue COVID manner at once both mechanistic explanatory. This has clear implications treatment such diseases.

Language: Английский

Citations

8

Increased fibrinaloid microclot counts in platelet-poor plasma are associated with Long COVID DOI Creative Commons
Caroline Dalton,

Madalena Oliveira,

Prachi Stafford

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 5, 2024

Abstract Outcomes following SARS-CoV-2 infection are variable; whilst the majority of patients recover without serious complications, a subset develop prolonged illness termed Long COVID or post-acute sequelae (PASC). The pathophysiology underlying remains unclear but appears to involve multiple mechanisms including persistent inflammation, coagulopathy, autoimmunity, and organ damage. Studies suggest that microclots, also known as fibrinaloids, play role in COVID. In this context, we developed method quantify microclots investigated relationship between microclot counts We show cohort, platelet-poor plasma from samples had higher count compared control groups retained wide distribution counts. Recent COVID-19 infections were seen be associated with than equivalent subsequent time-dependent reduction Our findings could potential biomarker disease and/or treatment target some patients.

Language: Английский

Citations

8

Long-term hypercoagulability, endotheliopathy and inflammation following acute SARS-CoV-2 infection DOI
Andrea Boccatonda, Elena Campello, Chiara Simion

et al.

Expert Review of Hematology, Journal Year: 2023, Volume and Issue: 16(12), P. 1035 - 1048

Published: Nov. 28, 2023

Introduction both symptomatic and asymptomatic SARS-CoV-2 infections – coined Coronavirus disease 2019 (COVID-19) have been linked to a higher risk of cardiovascular events after recovery.

Language: Английский

Citations

16

Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases? DOI Creative Commons
Douglas B. Kell, Etheresia Pretorius

Biochemical Journal, Journal Year: 2023, Volume and Issue: 480(15), P. 1217 - 1240

Published: Aug. 16, 2023

It is now well established that the blood-clotting protein fibrinogen can polymerise into an anomalous form of fibrin amyloid in character; resultant clots and microclots entrap many other molecules, stain with fluorogenic stains, are rather resistant to fibrinolysis, block up microcapillaries, implicated a variety diseases including Long COVID, have been referred as fibrinaloids. A necessary corollary this polymerisation generation novel epitopes proteins would normally be seen ‘self’, otherwise immunologically silent. The precise conformation resulting fibrinaloid (that, prions classical proteins, adopt multiple, stable conformations) must depend on existing small molecules metal ions may (and some cases known to) bound before polymerisation. Any such epitopes, however, likely lead autoantibodies. convergent phenomenology, distinct conformations seeding for initiation propagation, emerging link knowledge prions, prionoids, amyloids We here summarise evidence above reasoning, which has substantial implications our understanding genesis autoimmunity possible prevention thereof) based primary process formation.

Language: Английский

Citations

15

A Perspective on How Fibrinaloid Microclots and Platelet Pathology May be Applied in Clinical Investigations DOI Creative Commons
Etheresia Pretorius, Douglas B. Kell

Seminars in Thrombosis and Hemostasis, Journal Year: 2023, Volume and Issue: 50(04), P. 537 - 551

Published: Sept. 25, 2023

Abstract Microscopy imaging has enabled us to establish the presence of fibrin(ogen) amyloid (fibrinaloid) microclots in a range chronic, inflammatory diseases. Microclots may also be induced by variety purified substances, often at very low concentrations. These molecules include bacterial inflammagens, serum A, and S1 spike protein severe acute respiratory syndrome coronavirus 2. Here, we explore which properties these might used contribute differential clinical diagnoses prognoses various diseases with they associated. Such distributions their size number before after addition exogenous thrombin, spectral properties, diameter fibers are made, resistance proteolysis proteases, cross-seeding ability, concentration dependence ability bind small including fluorogenic stains. Measuring microclot parameters, together microscopy itself, along methodologies like proteomics flow cytometry, as well more conventional assays such those for cytokines, open up possibility much finer use generative methods future where personalized medicine will standard procedures all clotting pathology disease diagnoses.

Language: Английский

Citations

15