Animation: "Thrombus formation due to mechanical disruption of the endothelium"

Section 1

Length of Video Animation (no audio): 36 seconds

Overview

  1. Some patient types are more likely to develop thrombus than others.
  2. Patients with diabetes are hypercoagulable, and will develop thrombus more readily than patients without diabetes.
  3. Patients with complex lesions may be more prone to thrombus formation than those with simple lesions due to the mechanical challenges that these procedures create.

This sequence illustrates how coronary interventions can lead to plaque abrasion and rupture, resulting in thrombus formation, and, potentially, cardiac ischemia and tissue injury.

Focusing in on the heart, the left anterior descending (LAD) artery and its branches become clearly visible. Zooming in on the LAD, an atherosclerotic plaque has formed within the artery proximal to a bifurcation, thus reducing blood flow within the vessel.

Some patient types are more likely to develop thrombus than others. Patients with diabetes are already hypercoagulable before the procedure, and will develop thrombus more readily than patients without diabetes. Additionally, patients with complex lesions may also be more prone to thrombus formation since more extensive mechanical manipulation is required to complete their procedures. This type of manipulation can cause more mechanical damage to the endothelium than angioplasty on a simple lesion, as it often requires more stents and the procedure time is longer.

Section 2

Length of Video Animation (no audio): 20 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 for vessel flow and future thrombus formation.
  5. Stents are thrombogenic.

A small quantity of red blood cells and inactivated platelets can be seen flowing past a large plaque. Due to the extent of the plaque, blood flow is severely limited and there is a risk of plaque occlusion and consequent ischemia in the surrounding muscle tissue – percutaneous coronary intervention (PCI) is required.

A guide wire is inserted into the vessel, followed by a balloon and a stent. Inflation of the balloon is successful in flattening the plaque and opening up the vessel to enable the restoration of blood flow. However, the intervention abrades the surface and ruptures the plaque, dislodging sections – clearly visible on removal of the balloon – and causing deep, vertical cracks to appear in the plaque. Formation of these cracks exposes collagen in the vessel wall.

When a plaque ruptures, a number of intracellular platelet activators are released into the bloodstream, both from the vessel wall and from the activated platelets in the vicinity. These include: serotonin, epinephrine, platelet activating factor (PAF), thrombin, adenosine diphosphate (ADP), thromboxane A2 (TXA2), vasopressin, and collagen.

Intravascular collagen is a key platelet activator. When a plaque ruptures, collagen becomes exposed to blood flow and acts as a very strong activator of platelets. On contact with platelets, collagen causes a physical change in their appearance, such that they transform from a smooth, inactivated form into an irregular activated form, and GP IIb/IIIa receptors are expressed on their surfaces.

The disruption caused to the plaque by intervention initiates the coagulation cascade in the vessel, resulting in a chain of reactions that includes the production of fibrinogen. Fibrinogen acts as a ligand between the GP IIb/IIIa receptors on activated platelets, enabling them to aggregate and bind to endothelial cells and the plaque surface.

After the guide wire and balloon are removed, the focus becomes the surface of the stent and the surrounding plaque. It can bee seen that activated platelets are beginning to aggregate and adhere to the damaged plaque. As a consequence, a thrombus develops and grows with the adherence of more and more platelets. Platelets can be seen adhering to the thrombogenic struts of the stent.

Thrombus may or may not be visible on angiograms since it is only visible when a sufficient quantity is present to displace dye. 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): 40 seconds

Overview

  1. The effect of a single embolus is multiplied many times over in patients with complex lesions or diabetes.
  2. Only a small amount of thrombus is required to create platelet emboli, which 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 patients with complex lesions or diabetes.

The process of thrombus development is very dynamic, involving a continual cycle of platelet aggregation and thrombus breakdown. Thus, as the plaque enlarges, sections become dislodged and create platelet emboli, which shower downstream through the narrowing, bifurcating blood vessels into the microvasculature. As an 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, and preventing oxygen-carrying red blood cells from passing through the microvessels. This results in cell damage and death because the oxygen exchange that occurs in the capillary bed to feed the heart tissue is threatened.

It is important to note that this animation represents the course of a single embolus. This effect is multiplied many times over in patients with complex lesions or diabetes. It is therefore critical to manage both seen and unseen thrombus in these patients.

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