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Thrombus

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Thrombus

A thrombus (pl. thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulation step in hemostasis in or out of the circulatory system. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cross-linked fibrin protein. The substance making up a thrombus is sometimes called cruor. A thrombus is a healthy response to injury intended to stop and prevent further bleeding, but can be harmful in thrombosis, when a clot obstructs blood flow through a healthy blood vessel in the circulatory system.

In the microcirculation consisting of the very small and smallest blood vessels the capillaries, tiny thrombi known as microclots can obstruct the flow of blood in the capillaries. This can cause a number of problems particularly affecting the alveoli in the lungs of the respiratory system resulting from reduced oxygen supply. Microclots have been found to be a characteristic feature in severe cases of COVID-19 and in long COVID.

Mural thrombi are thrombi that adhere to the wall of a large blood vessel or heart chamber. They are most commonly found in the aorta, the largest artery in the body, more often in the descending aorta, and less often in the aortic arch or abdominal aorta. They can restrict blood flow but usually do not block it entirely. They appear grey-red along with alternating light and dark lines (known as lines of Zahn) which represent bands of white blood cells and red blood cells (darker) entrapped in layers of fibrin.

Thrombi are classified into two major groups depending on their location and the relative amount of platelets and red blood cells. The two major groups are:

In the microcirculation consisting of the very small and smallest blood vessels, the capillaries, tiny thrombi (microthrombi) known as microclots can obstruct the flow of blood in the capillaries. Microclots are small clumps of blood that form within the circulation, possibly as a result of a larger thrombus breaking down into smaller pieces or more likely by accretion. They can be a cause for concern as they can lead to blockages in small vessels and restrict blood flow, leading to tissue damage and potentially causing ischemic events. This can in turn lead to a form of chronic ischaemia-reperfusion injury and to the generation of autoantibodies. Because of their amyloid nature they are somewhat resistant to thrombolytic agents, which, along with the presence of certain other proteins, explains their persistence. Evidence based on the proteomes of such microclots implies that the macroclots formed in other diseases should also be amyloid in character; this has been shown for ischaemic stroke.

Microclots can cause a number of problems particularly affecting the alveoli in the lungs of the respiratory system, resulting from reduced oxygen supply. Microclots have been found to be a characteristic feature in severe cases of COVID-19, and in long COVID. Fibrinaloid microclots can be induced directly via the addition of SARS-CoV-2 spike protein to 'healthy' plasma, and the fact that the amyloidogenic potential of the spike variant is related to its virulence provides a strong indication that the microclots are on the aetiological pathway of Long Covid.

The fibrinaloid microclots also provide a ready explanation for other phenomena such as Postural Orthostatic Tachycardia Syndrome (POTS), atrial fibrillation, and fibromyalgia.

Fibrinaloid microclots are easily measured using techniques such as fluorescence microscopy and flow cytometry ('flow clotometry').

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