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Venous thromboembolism (VTE) encompasses deep venous thrombosis (DVT) and pulmonary embolism (PE) and causes cardiovascular death and disability as well as psychological illness and emotional distress. In the United States, the Surgeon General estimates that there are 100,000 to 180,000 deaths annually from PE and has declared that PE is the most common preventable cause of death among hospitalized patients. In a Canadian study, almost half of PE patients at 1 year had exercise limitation, decreased walking distance, or dyspnea, which lowered their quality of life. Survivors may suffer the complications of chronic thromboembolic pulmonary hypertension or postthrombotic syndrome. Chronic thromboembolic pulmonary hypertension causes breathlessness, especially with exertion. Postthrombotic syndrome (also known as chronic venous insufficiency) damages the venous valves of the leg and worsens the quality of life by causing ankle or calf swelling and leg aching, especially after prolonged standing. In its most severe form, postthrombotic syndrome causes skin ulceration (Fig. 273-1).
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Inflammation and Platelet Activation
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Virchow’s triad of venous stasis, hypercoagulability, and endothelial injury leads to recruitment of activated platelets, which release microparticles. These microparticles contain proinflammatory mediators that bind neutrophils, stimulating them to release their nuclear material and form web-like extracellular networks called neutrophil extracellular traps. These prothrombotic networks contain histones that stimulate platelet aggregation and promote platelet-dependent thrombin generation. Venous thrombi form and flourish in an environment of stasis, low oxygen tension, and upregulation of proinflammatory genes.
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The two most common autosomal dominant genetic mutations are factor V Leiden, which causes resistance to the endogenous anticoagulant, activated protein C (which inactivates clotting factors V and VIII), and the prothrombin gene mutation, which increases the plasma prothrombin concentration (Chaps. 61 and 113). Antithrombin, protein C, and protein S are naturally occurring coagulation inhibitors. Deficiencies of these inhibitors are associated with VTE but are rare. Antiphospholipid antibody syndrome is the most common acquired cause of thrombophilia and is associated with venous or arterial thrombosis. Other common predisposing factors include cancer, obesity, cigarette smoking, systemic arterial hypertension, chronic obstructive pulmonary disease, chronic kidney disease, blood transfusion, long-haul air travel, air pollution, estrogen-containing contraceptives, pregnancy, postmenopausal hormone replacement, surgery, and trauma. Inflammation predisposes to thrombosis, and conditions such as psoriasis and inflammatory bowel disease have become recognized risk factors of VTE. Sedentary lifestyle is an increasingly prevalent etiology of fatal PE. A Japanese study found that each 2 h per day increment of television watching is associated with a 40% increased likelihood of fatal PE.
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When deep venous thrombi (Fig. 273-2) detach from their site of formation, they embolize to the vena cava, right atrium, ...