Arterial and venous thromboses are major causes of morbidity and mortality rates. Arterial thrombosis is the most common cause of acute myocardial infarction (MI), ischemic stroke, and limb gangrene, whereas deep-vein thrombosis (DVT) leads to pulmonary embolism (PE), which can be fatal, and to the postphlebitic syndrome. 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 to arterial thrombi, 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, where they are triggered by stasis. Sluggish blood flow in these veins 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. Local thrombus formation is exacerbated by reduced clearance of activated clotting factors as a result of impaired blood flow. If the thrombi extend into 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 and fibrin, 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. 118-1). With the predominance of platelets in arterial thrombi, strategies to inhibit or treat arterial thrombosis focus mainly on antiplatelet agents, although, in the acute setting, they 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. The latter can also be used as an adjunct to anticoagulants for treatment of patients with extensive iliofemoral-vein thrombosis.
Classification of antithrombotic drugs.
Role of Platelets in Arterial Thrombosis