• In normal hemostasis and with a healthy endothelium, there is a balance between antithrombotic and prothrombotic molecules.¹

• Antithrombotic molecules released by the endothelium include:

  - Nitric oxide (NO) and prostacyclin (PGI₂), which prevent platelet adhesion and aggregation

  - Enzymes such as the ADPase CD39, which metabolizes the platelet activator adenosine diphosphate

  - Thrombomodulin (TM) and heparin sulfate (HS), which inactivate thrombin

  - Tissue-type plasminogen activator (TPA), which converts plasminogen to plasmin, a protease that degrades fibrin

• Prothrombotic molecules include:

  - von Willebrand factor (vWF) and P-selectin, which mediate platelet adhesion to the endothelium

  - Tissue factor (TF), which initiates the coagulation cascade (discussed in a later slide)

  - Plasminogen activator inhibitor-1 (PAI-1)

• Endothelial injury disrupts this balance. Atherosclerosis is characterized by a hypercoagulable state at all stages of the disease.

• Thus, antithrombotic strategies are central to management and prevention of ACS.

¹ Ruggeri ZM. Platelets in atherothrombosis. Nat Med. 2002;8:1227-1234.