Figure 6.

Cangrelor Limits Thrombus Outer Shell Formation

An arterial thrombus is composed of distinct regions based on the primary mechanism of platelet activation (28). Thrombin is believed to drive platelet activation in the early phase of thrombus formation, resulting in a tightly packed core region (dark area) that limits its diffusion to the surface exposed to flowing blood. Further growth is reliant on adenosine diphosphate (ADP) release and thromboxane A2 generation by the outer layer of adherent platelets, enabling the recruitment of additional platelets that form the less dense shell region (green area). Cangrelor (orange dots) primarily targets the outer shell by blocking P2Y₁₂ receptor-mediated platelet activation (inset). Both the core and outer shell formation are critically reliant on integrin αIIbβ3-mediated platelet adhesion as blockade with abciximab nearly abrogates thrombus formation (inset).