Animation: "In PCI, ReoPro diminishes existing thrombus"

Section 1

Length of Video Animation (no audio): 33 seconds

Overview

  1. Thrombus is sometimes present before PCI is initiated, particularly in patients with AMI, diabetes, UA/NSTEMI, and complex lesions.
  2. Thrombus may or may not be visible on an angiogram of the vessel.
  3. The administration of ReoPro before PCI can help to relieve the vessel of some of the obstructive thrombus, and thus improve flow.

Thrombus is often present before the procedure starts – particularly in patients with acute myocardial infarction (AMI), complex lesions, unstable angina, or non-ST-segment elevation MI (UA/NSTEMI). A study by White et al1 indicates that thrombus is often present in patients with complex lesions before the procedure starts. Thrombus may or may not be visible on an angiogram of the vessel due to the fact that it is only visible when there is a sufficient quantity to displace dye.

This view begins the sequence with a view of a diseased coronary vessel containing a large lesion. A tear can be seen in the plaque – toward the lower end of the screen – indicating that spontaneous plaque rupture has occurred. As a result, the exposure of intravascular collagen has caused platelet activation, and subsequent aggregation, to occur. Consequently, a large thrombus has formed at the site of the plaque, which has severely restricted blood flow, such that the vessel is almost completely occluded.

ReoPro (represented as a teal green cloud) can be seen flowing through the damaged vessel and past the plaque. As a result, the outermost platelets begin to break away from the collected white clot, and the thrombus starts to diminish. Improvement of blood flow through the vessel can be seen. Thus, the administration of ReoPro before PCI can help to relieve the vessel of some obstructive thrombus and improve blood flow.

Reference:

  1. White CJ, Ramee SR, Collins TJ, et al. Coronary Thrombi Increase PTCA Risk. Circulation 1996;93:253-258.
    2.

Section 2

Length of Video Animation (no audio): 50 seconds

Overview

  1. ReoPro administration, after thrombus formation, prevents further thrombus growth. This is the most important goal.
  2. In white clots, ReoPro takes advantage of the dynamic binding of fibrinogen by binding to GP IIb/IIIa receptors that have been abandoned by fibrinogen. This causes platelets to disaggregate and the platelet mass to diminish in size.
  3. The properties of ReoPro help to improve blood flow in the vessel during PCI.
  4. Improved blood flow maintains patency in the microvasculature and promotes oxygen exchange at the tissue level.
  5. With the aid of ReoPro, platelets circulate freely and interventions can proceed with a lower risk of complications due to thrombus formation.

Zooming in to the cellular level, it can be seen that numerous fibrinogen molecules (blue) – a ligand, which enables platelets to aggregate have become bound to the GP IIb/IIIa receptors on activated platelets, causing them to aggregate. As ReoPro is given, it takes advantage of the dynamic nature of the fibrinogen binding process (fibrinogen continually binds to, and dissociates from, the GP IIb/IIIa receptors) and blocks the GP IIb/IIIa receptors once they have been abandoned by fibrinogen. As a result of the repetition of this process, the platelets can be seen separating from one another, the platelet mass decreasing in size, and numerous free-flowing fibrinogen molecules in the blood. ReoPro is a non-competitive inhibitor of the GP IIb/IIIa receptor and has a very strong affinity for the receptor. This allows ReoPro to maintain its position on the GP IIb/IIIa receptor.

Looking at the vasculature, an embolus that has become detached from the area of injury can be seen. Without ReoPro, this thrombus would eventually become lodged in the microvasculature, causing an occlusion and potentially ischemia. However, because ReoPro has been administered, we see the embolus gradually diminish in size, and the clearance of the disaggregated platelets through the microvasculature. Diminishing the thrombus load improves circulation in the distal vasculature, thus maintaining patency and enabling healthy oxygen exchange at the tissue level. With the aid of ReoPro, platelets circulate freely and interventions can proceed with a lower risk of complications due to thrombus formation.

A balloon and stent are inserted into the ReoPro-treated vessel to open up the lesion and restore blood flow. Intervention results in the flattening and cracking of the plaque, and the dislodging of sections of the plaque. Without ReoPro, this would normally result in significant platelet aggregation. However, with ReoPro, the resultant platelet aggregation is prevented, such that blood begins to flows freely through the stent.

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