Hemostasis is the physiologic response to bleeding that occurs when a vessel wall is disrupted and is regulated through several processes. 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 precludes 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 Thrombosis may occur when the quantity of platelets is low or their function is inhibited. This distinction is important when considering defined hypercoagulable states and the role they may play in venous thrombosis.
MECHANISMS OF VENOUS THROMBOSIS
Virchow's triad has been the basis of our understanding of the mechanisms that lead to thrombus formation in the venous system. Virchow postulated that changes in the vessel wall, venous stasis, and hypercoagulability of the blood lead to thrombus formation.4 This underlying principle has been applied to many clinical situations.
A healthy endothelium is nonthrombogenic. However, changes in the endothelial surface brought on by inflammation, injury, or damage lead to initiation of thrombus formation by expression of tissue factor and subsequent activation and aggregation of platelets. Endothelial damage may be caused by direct trauma, exposure to endotoxins, inflammatory cytokines, thrombin, or low oxygen tension.5 Injured endothelial cells release tissue factor and plasminogen activator inhibitor-1 (PAI-1) and internalize thrombomodulin, which leads to thrombus formation. They also produce less tissue plasminogen activator (tPA), the principal activator of fibrinolysis, which further promotes thrombosis.6 The presence of functional platelets is not necessary for the initiation or propagation of thrombosis on these damaged surfaces.
Venous flow is supported by the calf muscles, and venous pooling is prevented by venous valves. Venous stasis can be produced by immobility (hospitalization, surgery, stroke), increased venous pressure (varicose veins, venous insufficiency, heart failure), and medical conditions that increase blood viscosity (paraproteinemia, cryoglobulinemia, myeloproliferative disorders).