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Venous thromboembolism (VTE), which encompasses deep-vein thrombosis (DVT) and pulmonary embolism, is one of the three major cardiovascular causes of death along with myocardial infarction and stroke. VTE can cause death from pulmonary embolism or, among survivors, chronic thromboembolic pulmonary hypertension and postphlebitic syndrome. The U.S. Surgeon General has declared that pulmonary embolism is the most common preventable cause of death among hospitalized patients. Medicare has labeled PE and DVT occurring after total hip or knee replacement as unacceptable "never events" and no longer reimburses hospitals for the incremental expenses associated with treating this postoperative complication. New nonprofit organizations have begun educating health care professionals and the public on the medical consequences of VTE along with risk factors and warning signs.

Between 100,000 and 300,000 VTE-related deaths occur annually in the United States. Mortality rates and length of hospital stay are decreasing as charges for hospital care increase. Approximately three of four symptomatic VTE events occur in the community, and the remainder are hospital acquired. Approximately 14 million hospitalized patients are at moderate to high risk for VTE in the United States annually: 6 million major surgery patients and 8 million medical patients with comorbidities such as heart failure, cancer, and stroke. The prophylaxis paradigm has changed from voluntary to mandatory compliance with guidelines to prevent VTE among hospitalized patients. With an estimated 370,000 pulmonary embolism-related deaths annually in Europe, the projected direct cost for VTE-associated care exceeds 3 billion euros per year. In Japan, as the lifestyle becomes more westernized, the rate of VTE appears to be increasing.

The long-term effects of nonfatal VTE lower the quality of life. Chronic thromboembolic pulmonary hypertension is often disabling and causes breathlessness. A late effect of DVT is postphlebitic syndrome, which eventually occurs in more than half of DVT patients. Postphlebitic syndrome (also known as postthrombotic syndrome or chronic venous insufficiency) is a delayed complication of DVT that causes the venous valves of the leg to become incompetent and exude interstitial fluid. Patients complain of chronic ankle or calf swelling and leg aching, especially after prolonged standing. In its most severe form, postphlebitic syndrome causes skin ulceration, especially in the medial malleolus of the leg. There is no effective medical therapy for this condition.

Prothrombotic states

Thrombophilia contributes to the risk of venous thrombosis. The two most common autosomal dominant genetic mutations are factor V Leiden, which causes resistance to activated protein C (which inactivates clotting factors V and VIII), and the prothrombin gene mutation, which increases the plasma prothrombin concentration (Chaps. 3 and 21). Antithrombin, protein C, and protein S are naturally occurring coagulation inhibitors. Deficiencies of these inhibitors are associated with VTE but are rare. Hyperhomocysteinemia can increase the risk of VTE, but lowering the homocysteine level with folate, vitamin B6, or vitamin B12...

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