Fibrinaloid Microclots-Induced Microcirculation Dysfunction: Mechanism and Laser-Based Haemodynamic Validation

Abstract

The microcirculation typically refers to those capillaries less than 100 μm in diameter. We have shown that blood can clot into an anomalous amyloid form, manifesting as microclots of typically 2–200 μm equivalent diameter that are rather resistant to fibrinolysis. Because they contain fibrin and other proteins in an amyloid form, we have referred to them as fibrinaloid microclot complexes. We have also previously developed the idea that endothelial dysfunction can both lead to and be caused by the fibrinaloid microclots so formed, such that this can slow or block entirely parts of the microcirculation. The microclots might be thought of as a ‘structural’ manifestation in that they are actual, observable structures. This impairment of the microcirculation is referred to in Traditional Chinese Medicine (TCM) as ‘blood stasis’. It is thus desirable to have ‘functional’ methods that can measure these effects on the microcirculation directly. As a complement to a recent survey of nailfold capillaroscopy, the present paper provides a wide-ranging review of the utility of laser speckle imaging (LSI) and laser Doppler imaging (LDI) for assessing the microcirculation in a large variety of diseases in which it is considered to be involved. These include Long COVID, sepsis, and ischaemic stroke. In all cases in which fibrinaloid microclots have been observed, so too do these methods detect an impairment of the microcirculation. Notably, blood pressure is raised while blood flow in the microcirculation is lower; this clearly speaks to occlusion and/or capillary rarefaction, and indicates that the raised blood pressure is the effect and not the cause of the decrease in flow rate or stasis of the microcirculation. As rapid, information-rich and non-invasive methods, LSI and LDI seem to have outstanding potential for assessing the role of fibrinaloid microclots in affecting blood stasis in the microcirculation, in a huge variety of inflammatory diseases and syndromes.

Keywords

Clotting / Amyloid / Fibrinaloid / Laser-doppler imaging / Laser speckle imaging / Cross-seeding / Fibrils / Microcirculation

Acknowledgments

D.B.K. thanks Brian Lock (Moor Instruments) for useful discussions.

Author Contributions

Conceptualization, D.B.K., E.P. and H.Z.; Formal Analysis, D.B.K., E.P. and H.Z.; Resources, D.B.K. and E.P.; Writing—Original Draft Preparation, D.B.K.; Writing—Review & Editing, D.B.K., E.P. and H.Z.; Visualization, D.B.K. and E.P.; Funding Acquisition, D.B.K. and E.P.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Funding

D.B.K. thanks the Balvi Foundation (grant 18) and the Novo Nordisk Foundation for funding (grant NNF20CC0035580). E.P. thanks PolyBio Research Foundation and Kanro Foundation for funding. The content and findings reported and illustrated are the sole deduction, view, and responsibility of the researchers and do not reflect the official position and sentiments of the funders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Declaration of Competing Interests

E.P. is a named inventor on a patent disclosing the use of fluorescence microscopy in Long COVID.

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