Preprint Inflammatory Triggers, Cell Death, Membrane Damage and Lipid Asymmetry That Shape Procoagulant Surfaces for Amyloidogenic Microclotting

[mariovitali]

Etheresia Pretorius,Chantelle Venter,Jean M. Nunes,Alain R. Thierry,Douglas B. Kell​

Abstract​

Hypercoagulability, immunothrombosis, and protein misfolding are deeply interconnected processes that converge on cell membranes as central orchestrators of thrombo-inflammation. In health, membrane lipid asymmetry, intact glycocalyx, and regulated receptor activity maintain vascular homeostasis. During inflammation or cell death, however, phosphatidylserine (PS) externalization, protein unfolding, and damage to glycosaminoglycans expose negatively charged, amyloidogenic surfaces that attract coagulation factors, inflammatory mediators, and adhesion proteins. These events generate catalytic sites for prothrombinase assembly. We review how cellular debris, microparticles, immune complexes such as neutrophil extracellular traps, and amyloidogenic plasma proteins, including serum amyloid A, interact with fibrinogen to form circulating (heterogeneous) procoagulant complexes, we term fibrinaloid microclot complexes (FMCs). Distinct from canonical fibrin clots, these FMCs display β-sheet–rich features, ThT-binding, and resistance to fibrinolysis, implicating them as key drivers of vascular pathology in inflammatory (and post-viral) syndromes. Recognizing different FMC phenotypes, mechanisms, and biochemical composition of these circulating complexes provides new insights into the pathogenesis of systemic inflammatory diseases, and highlights their potential as both diagnostic markers and therapeutic targets.


Link : https://www.preprints.org/manuscript/202510.1460

 

[mariovitali]

@DMissa and @TamaraRC please have a look at this. Extensive content on the role of Phosphatidylserine (PS) and phospholipids. Also mentions efferocytosis.

 

[DMissa]

@DMissa and @TamaraRC please have a look at this. Extensive content on the role of Phosphatidylserine (PS) and phospholipids. Also mentions efferocytosis.

we have an efferocytosis lab or two next door, i will have to chat with them

 

[Violeta]

Do you think the pro resolving mediators would help dissolve the fibrinaloid microclot complexes. Or if it can't break up the clots, at least perhaps decrease the amount formed.

Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia.

The T-series of resolvins (RvTs) reduce the formation of neutrophil extracellular traps (NETs) and enhance NET clearance by macrophages​

 

[Jonathan Edwards]

Do you think the pro resolving mediators would help dissolve the fibrinaloid microclot complexes. Or if it can't break up the clots, at least perhaps decrease the amount formed.

As far as I know we still have no evidence for the existence of microclots in human beings. If they were there in blood samples they would have been centrifuged out when plasma is prepared. The 'microclots' reported appear to be in vitro artefacts. The abstract in the first post makes no sense in terms of the biology I was taught. I am not sure that anyone except Pretorius believes in it.