Thromboembolic disorders are major causes of morbidity and mortality. Thrombosis can occur in arteries or veins. Arterial thrombosis is the most common cause of acute myocardial infarction (MI), ischemic stroke, and limb gangrene. Venous thromboembolism encompasses deep vein thrombosis (DVT), which can lead to postthrombotic syndrome, and pulmonary embolism (PE), which can be fatal or can result in chronic thromboembolic pulmonary hypertension.
Most arterial thrombi are superimposed on disrupted atherosclerotic plaque because plaque rupture exposes thrombogenic material in the plaque core to the blood. This material then triggers platelet aggregation and fibrin formation, which results in the generation of a platelet-rich thrombus that can temporarily or permanently occlude blood flow. In contrast, venous thrombi rarely form at sites of obvious vascular disruption. Although they can develop after surgical trauma to veins or secondary to indwelling venous catheters, venous thrombi usually originate in the valve cusps of the deep veins of the calf or in the muscular sinuses. Sluggish blood flow reduces the oxygen supply to the avascular valve cusps. Endothelial cells lining these valve cusps become activated and express adhesion molecules on their surface. Tissue factor–bearing leukocytes and microparticles adhere to these activated cells and induce coagulation. DNA extruded from neutrophils forms neutrophil extracelluar traps (NETs) that provide a scaffold that traps red blood cells, promotes platelet adhesion and activation, and augments coagulation. Local thrombus formation is exacerbated by reduced clearance of activated clotting factors as a result of impaired blood flow. If the thrombi extend from the calf veins into the popliteal and more proximal veins of the leg, thrombus fragments can dislodge, travel to the lungs, and produce a PE.
Arterial and venous thrombi are composed of platelets, fibrin, and trapped red blood cells, but the proportions differ. Arterial thrombi are rich in platelets because of the high shear in the injured arteries. In contrast, venous thrombi, which form under low shear conditions, contain relatively few platelets and are predominantly composed of fibrin and trapped red cells. Because of the predominance of platelets, arterial thrombi appear white, whereas venous thrombi are red in color, reflecting the trapped red cells.
Antithrombotic drugs are used for prevention and treatment of thrombosis. Targeting the components of thrombi, these agents include (1) antiplatelet drugs, (2) anticoagulants, and (3) fibrinolytic agents (Fig. 24-1). With the predominance of platelets in arterial thrombi, strategies to attenuate arterial thrombosis focus mainly on antiplatelet agents, although, in the acute setting, often include anticoagulants and fibrinolytic agents. Anticoagulants are the mainstay of prevention and treatment of venous thromboembolism because fibrin is the predominant component of venous thrombi. Antiplatelet drugs are less effective than anticoagulants in this setting because of the limited platelet content of venous thrombi. Fibrinolytic therapy is used in selected patients with venous thromboembolism. For example, patients with massive or submassive PE can benefit from systemic or catheter-directed fibrinolytic therapy. Pharmaco-mechanical therapy also is used ...