Abstract
Platelets have long been considered simple anucleate cells that rapidly adhere and
aggregate at sites of vascular injury. However, recent in vivo experimental data have
shed new light on the platelet response to vascular injury. These data have unexpectedly
revealed that platelet thrombus formation is a highly dynamic process and yields a
platelet thrombus with a distinct hierarchical structure composed of a “core” of highly
activated platelets and a “shell” of platelets in a low activation state. This has
given rise to the concept that therapeutic targeting of the propagating thrombus shell
may hold promise as a means to target thrombosis while sparing hemostasis. While platelets
have been historically considered central to arterial thrombosis, they have been traditionally
viewed as minor contributors to the formation of venous thrombosis. However, this
concept has recently been challenged with the emergence of a large body of evidence
highlighting the important proinflammatory function of platelets. The proinflammatory
function of platelets is afforded by their ability to induce neutrophil extracellular
trap formation, enhance leucocyte recruitment, and secrete granular contents such
as high mobility group protein B1 and polyphosphate. These proinflammatory processes
trigger coagulation, via the intrinsic pathway, and are central to the formation of
venous thrombosis, a condition now appreciated to be a form of sterile inflammation.
These data now place platelets at the center stage in orchestrating the thromboinflammatory
response underpinning venous thrombosis and have provided new hope that novel platelet-targeted
therapeutics may represent a safe and effective approach to prevent venous thrombosis.
Keywords
arterial thrombosis - venous thrombosis - platelets - antithrombotic - bleeding
