Thrombosis
Thrombosis and embolism are ultimately the main cause of death in the industrialized world. Thrombosis is inappropriate activation of haemostasis, with clots (thrombi) forming inside blood vessels. If thrombi fragment they can be carried in the blood as emboli, and block downstream blood vessels causing infarction. Most commonly fatalities are due to thrombosis as a result of atherosclerotic plaque rupture in acute coronary syndromes (see Chapter 42), or venous thromboembolism (VTE), particularly pulmonary embolism, following deep vein thrombosis (DVT). Virchow’s triad of endothelial damage, blood stasis and hypercoagulability predispose to thrombosis. Endothelial (or endocardial) damage is the most common cause of arterial thrombosis. Stasis (poor flow), which allows clotting factors to accumulate and unimpeded formation of thrombi, is the most common cause of DVT and VTE. Risk factors are shown in Figure 8a. Once formed, thrombi can undergo dissolution by fibrinolysis, propagation by accumulation of more fibrin and platelets, or organization with invasion of endothelial or smooth muscle cells and fibrosis. In recanalization channels form allowing blood to reflow. If not destroyed, thrombi may be incorporated into the vessel wall.
Arterial (white, platelet-rich) thrombi are primarily treated with antiplatelet drugs, while venous (red) thrombi are primarily treated with anticoagulants. All such therapies increase risk of bleeding, and may be contraindicated in patients with prior stroke, active ulcers, pregnancy or recent surgery.
Antiplatelet Drugs (Figure 8b)
Aspirin (acetylsalicylic acid) is the most important antiplatelet drug. It irreversibly inhibits cyclooxygenase (COX), the first enzyme in the sequence leading to formation of thromboxane A2 (TXA2) and prostacyclin (PGI2). TXA2 is produced by platelets and is a key platelet activator (see Chapter 7), whereas endothelium-derived PGI2 inhibits platelet activation and aggregation. Because aspirin inhibits COX irreversibly, production of PGI2 and TXA2
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