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Understanding arterial thrombosis

How do atherosclerotic plaques form?

The process of atherogenesis is initiated by disturbances in blood flow at so-called ‘predilection sites’, which lead to changes in the endothelial lining of the vascular system.1 These changes cause low-density lipoproteins (LDLs) to accumulate in the intima (the surface layer of the artery exposed to the blood), where they become modified by oxidation and aggregation.1

 

Increasing retention of LDL triggers the recruitment of inflammatory macrophages, which ingest the lipids to become foam cells.1,2 As the lesion progresses, these lipid-rich cells in the core of the plaque begin to die, releasing lipids and forming the necrotic core of the fibroatheroma.2 Meanwhile, smooth muscle cells migrate from the artery wall into the intima, where they proliferate to form a fibrous cap that covers the surface of the plaque.2

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Arterial thrombosis explained.
Video explaining the formation of arterial thromboses
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What are atherosclerotic plaques made of?

The composition of an atherosclerotic plaque changes as it develops. Initially, the plaque consists of an accumulation of low-density lipoproteins (LDLs).1 Eventually, inflammatory macrophages enter the intima (the surface layer of the artery exposed to the blood) and, after ingesting the LDL, become foam cells – so-called because they are filled with cholesteryl ester droplets, giving them a foamy appearance.1-3

 

The next major change in plaque morphology takes place once the lipid-rich cells begin to die and release their lipid contents into the now necrotic core.2 Simultaneously, a fibrous cap of smooth muscle cells begins to form. Over time, infiltrating macrophages and the release of active proteases can cause thinning of the cap and make rupture more likely.2

Formation of an arterial blood clot

Formation of an arterial blood clot.

How an arterial blood clot forms

 

Why do atherosclerotic plaques rupture?

Over time, loss of smooth muscle cells along with infiltrating macrophages and the release of active proteases can lead to thinning of a plaque’s fibrous cap, leading to vulnerable plaques that are at high short-term risk of rupture.1 The archetypal vulnerable plaque is characterized by a thin fibrous cap and an abundance of macrophage-derived foam cells beneath it.2 Eventually, the cap can no longer withstand the mechanical force of the blood pressure and the plaque may rupture.4

 

The majority of ischaemic events occur when a vulnerable plaque ruptures or is eroded, releasing procoagulant material into the bloodstream and leading to the formation of a thrombus – a process known as atherothrombosis.2 Alternatively, ischaemic events may be provoked by plaque erosion, a process that is poorly understood but results in the loss of the surface endothelium.1

Vulnerable arterial plaques have thin fibrous caps

A vulnerable plaque with a thin fibrous cap.

Structure of a vulnerable arterial plaque

 

How does atherothrombosis lead to an ischaemic event?

When a vulnerable plaque ruptures, the contents of the plaque become exposed to the blood with important clinical consequences:5

 

  • Exposure of tissue factor in the lipid core leads to thrombin generation and activation of the coagulation cascade, culminating in the cross-linking of fibrin, which stabilizes the clot5
  • At the same time, platelets adhere to collagen and von Willebrand factor in the subendothelial layer, resulting in the rapid recruitment of additional platelets to the site to form a platelet plug. Thrombin further contributes to activating platelets5

 

The activation of these two pathways concurrently allows for the generation of a thrombus with both fibrin- and platelet-rich parts.5

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The process of thrombus formation
Activation of the coagulation cascade and the platelet pathway results in thrombus formation

Consequences of atherothrombosis

Consequences of atherothrombosis.

Plaque rupture and superimposed thrombosis can result in stroke, myocardial infarction or acute limb ischaemia

What is the difference between arterial thrombosis and venous thrombosis?

Arterial and venous thrombosis differ in terms of the triggers involved and thrombus composition.6

 

Arterial thrombosis develops as the result of plaque rupture and endothelial disruption (for more information, please see the Understanding arterial thrombosis section).6 However, for venous thrombosis, the endothelium remains intact and thrombus formation is a result of abnormal blood flow, increased coagulability and altered vessel walls.6

 

Because of the different mechanisms of formation, arterial and venous clots have different compositions. Arterial clots are rich in platelets, which are rapidly recruited to the site of vascular injury.6 However, as a clot begins to reduce the flow of blood, a fibrin-rich component can form.5 Venous clots, on the other hand, are always rich in fibrin, which holds together trapped red blood cells.5

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Formation of venous thromboses

Formation of venous thromboses
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Formation of arterial thromboses

Formation of arterial thromboses
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Venous thrombosis is different from arterial thrombosis. More information on venous thrombosis can be found at ThrombosisAdviser.com

References
  • Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res 2014;114:1852–1866. Return to content
  • Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011;473:317–325. Return to content
  • Libby P, Lichtman AH, Hansson GK. Immune effector mechanisms implicated in atherosclerosis: from mice to humans. Immunity 2013;38:1092–1104. Return to content
  • Hansson GK, Libby P, Tabas I. Inflammation and plaque vulnerability. J Intern Med 2015;278:483–493. Return to content
  • Weitz JI. Insights into the role of thrombin in the pathogenesis of recurrent ischaemia after acute coronary syndrome. Thromb Haemost 2014;112:924–931. Return to content
  • Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008;451:914–918. Return to content

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