Hemostasis is the physiologic response to bleeding that occurs when a vessel wall is disrupted and is regulated through several processes. In the arterial hemostatic system, the first response is the activation, adhesion, and aggregation of platelets. The platelet plug that forms is stabilized by the deposition of fibrin, which is generated on the surface of the platelet membrane and on nearby disrupted vessel surfaces. The extent of thrombosis is limited by endogenous anticoagulant systems and by the fibrinolytic system, which preclude the development of thrombosis beyond the site of injury.1
Thrombosis is a pathologic process characterized by an inappropriate or exaggerated generation of clot. It may occur if there is vessel wall injury without disruption (i.e., no bleeding), or in the setting of excess activation of platelets or coagulation factors. Inadequate endogenous anticoagulant or fibrinolytic function may also contribute to the development of thrombosis.
In the arterial circulation, hemostasis and thrombosis are platelet dependent, where high shear stresses and potentially turbulent flow stimulate this mechanism and where the fibrinolytic system regulates secondary fibrin formation.2,3 By contrast, the venous system is characterized by low flow and stasis, permitting the development of hemostasis and thrombosis through activation of the coagulation cascade and regulation by endogenous anticoagulant proteins.1 This distinction is important when considering defined hypercoagulable states and the role they may play in peripheral arterial disease.
MECHANISM OF ARTERIAL HEMOSTASIS AND THROMBOSIS
The initiation of hemostasis or thrombosis in the arterial system is dependent on the platelet, with stabilization of the platelet plug with fibrin. The basic pathway and contributing factors are depicted in Figure 10-1.
Basic steps in arterial hemostasis. vWF, von Willebrand factor; PAF, platelet activation factor; TSP, thrombospondin; TBX A2, thromboxane A2; PAI-1, plasminogen activator inhibitor-1; TAFI, thrombin-activated fibrinolytic inhibitor; TFPI, tissue factor pathway inhibitor; tPA, tissue plaminogen activator; uPA, urokinase-like plaminogen activator.
Under normal conditions, platelets do not adhere to the normal endothelial surface of the arterial wall. If there is a disruption of the endothelial surface, platelets will spontaneously adhere to the exposed subendothelial matrix, medial wall, or adventitial layers. This adhesion is mediated by integrin receptors on the platelet surface, including glycoprotein (GP) Ia/IIa, which binds to collagen.2,3 Collagen may be the most important component of the subendothelial matrix for the initiation of platelet adhesion.4 von Willebrand factor (vWF) is also embedded in the subendothelial matrix,5 which is preferentially recognized over circulating plasma vWF by GP Ib/IX, another key integrin receptor on the platelet surface, creating platelet adhesion.2,5
Disruption of the smooth endothelial surface creates turbulent flow ...