Animation: "Spontaneous thrombus formation"

Section 1

Length of Video Animation (no audio): 32 seconds

Overview

  1. Patients with UA/NSTEMI often present with chest discomfort at rest. Their ECGs may be abnormal and their cardiac enzymes can be elevated.

Patients with unstable angina or non-ST-segment elevation myocardial infarction (UA/NSTEMI) often present to the hospital with chest pain at rest. Their electrocardiograms (ECGs) can be abnormal and their cardiac enzymes can be elevated. This sequence illustrates spontaneous thrombus formation within a diseased coronary vessel, which can result in cardiac ischemia and MI.

Focusing on the heart, the left anterior descending (LAD) artery and its branches are clearly visible. Zooming in on the LAD, it can be seen that an atherosclerotic plaque has formed within the artery proximal to a bifurcation, and this plaque is reducing blood flow within the vessel.

Section 2

Length of Video Animation (no audio): 23 seconds

Overview

  1. Plaque rupture induces the release of a number of intracellular platelet activators into the bloodstream. Many of these activators are inhibited by the antiplatelet and anticoagulant agents used during angioplasty.
  2. Collagen is a strong intravascular platelet activator that induces thrombus formation when exposed to blood flow. Collagen is unopposed by any of the adjunctive therapies used during angioplasty.
  3. Thrombus is only visible on angiograms when it is sufficiently large to displace dye.
  4. Thrombus that is not visible on angiograms can have consequences or vessel flow and future thrombus formation.

Entering the diseased vessel, it can be noted that red blood cells and inactivated platelets (identified by their smooth surfaces) are able to flow.

Spontaneous plaque rupture has occurred within the vessel. When a plaque ruptures and platelets become activated, a number of intracellular platelet activators are released into the bloodstream from both the vessel wall and the activated platelets in the vicinity. These include: serotonin, epinephrine, platelet activating factor (PAF), thrombin, adenosine diphosphate (ADP), thromboxane A2 (TXA2), and vasopressin. Collagen – a key platelet activator – is found in the vessel wall. When a plaque ruptures, collagen becomes exposed to the flowing blood and acts as a very strong activator of platelets. None of the adjunctive therapies used during angioplasty oppose collagen in its role as an activator of platelets.

The platelets, once activated, adopt a rough and uneven surface, and their GP IIb/IIIa receptors are expressed. In addition, platelets adhere to the area of injury, forming a platelet monolayer. As this process continues, a thrombus forms which may grow and occlude the vessel.

It is important to note that much of the thrombus that is present in a vessel will not be visible on an angiogram because it is only visible if there is a sufficient quantity to displace dye in the vessel. However, this "unseen" thrombus can have consequences for vessel flow and future thrombus formation, as do larger amounts of thrombus.

Section 3

Length of Video Animation (no audio): 28 seconds

Overview

  1. The effect of a single embolus is multiplied many times over in AMI and UA/NSTEMI patients.
  2. Only a small amount of thrombus is required to create platelet emboli. Platelet emboli can block the distal vasculature at the capillary bed.
  3. The capillary bed is the site of oxygen exchange, which serves to feed the heart tissue.
  4. Blockade of the distal vasculature by platelet emboli causes cell damage and death.
  5. It is important to manage both seen and unseen thrombus in UA/NSTEMI and AMI patients.

The process of thrombus development is very dynamic, involving a continual cycle of platelet aggregation and thrombus breakdown. Thus, as the thrombus enlarges, sections become dislodged and create platelet emboli, which shower downstream through the narrowing, bifurcating blood vessels into the microvasculature. As the embolus flows into the narrower vessels, it breaks down into multiple emboli, which become lodged in the microvessels, blocking the distal vasculature at the capillary bed. This results in cell damage and death because the oxygen exchange that occurs in the capillary bed to feed the heart tissue is threatened.

In this particular example, emboli have lodged in a bifurcating vessel, causing complete occlusion of both arms (and the inability of oxygen-carrying red blood cells to pass through), and consequent ischemia in the cardiac muscle supplied by that vessel.

It is important to note that this animation represents the course of a single embolus. This effect is multiplied many times over in UA/NSTEMI patients (and in AMI patients). It is therefore critical to manage both seen and unseen thrombus in these patients.

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