Venous thromboembolism (VTE), which encompasses deep venous thrombosis (DVT) and pulmonary embolism (PE), is one of the three major cardiovascular causes of death, along with myocardial infarction and stroke. VTE can cause death from PE or, among survivors, chronic thromboembolic pulmonary hypertension and postphlebitic syndrome. The U.S. Surgeon General has declared that PE 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 (M) hospitalized patients are at moderate to high risk for VTE in the United States annually: 6 M major surgery patients and 8 M 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 PE-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 one-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.
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. 58 and 117). 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 does not reduce the incidence of VTE. 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, systemic arterial hypertension, chronic obstructive pulmonary disease, long-haul air travel, air pollution, obesity, cigarette smoking, eating large amounts of red meat, oral contraceptives, pregnancy, postmenopausal hormone replacement, surgery, and trauma.
When venous thrombi are dislodged from their site of formation, they embolize to the pulmonary arterial circulation or, paradoxically, to the arterial circulation through a patent foramen ovale or atrial septal defect. About one-half of patients with pelvic vein thrombosis or proximal leg DVT develop PE, which is often asymptomatic. Isolated calf vein thrombi pose a much lower risk of PE but are the most common source of paradoxical embolism. These tiny thrombi can traverse a patent foramen ovale or atrial septal defect, unlike larger, more proximal leg thrombi. With increased use of chronic indwelling central venous catheters for hyperalimentation and chemotherapy, as well as more frequent insertion of permanent pacemakers and internal cardiac defibrillators, upper extremity venous thrombosis is becoming a more common problem. These thrombi rarely embolize and cause PE.
The most common gas exchange abnormalities are hypoxemia (decreased arterial Po2) and an increased alveolar-arterial O2 tension gradient, which represents the inefficiency of O2 transfer across the lungs. Anatomic dead space increases because breathed gas does not enter gas exchange units of the lung. Physiologic dead space increases because ventilation to gas exchange units exceeds venous blood flow through the pulmonary capillaries.
Other pathophysiologic abnormalities include the following:
Increased pulmonary vascular resistance due to vascular obstruction or platelet secretion of vasoconstricting neurohumoral agents such as serotonin. Release of vasoactive mediators can produce ventilation-perfusion mismatching at sites remote from the embolus, thereby accounting for a potential discordance between a small PE and a large alveolar-arterial O2 gradient.
Impaired gas exchange due to increased alveolar dead space from vascular obstruction, hypoxemia from alveolar hypoventilation relative to perfusion in the nonobstructed lung, right-to-left shunting, and impaired carbon monoxide transfer due to loss of gas exchange surface.
Alveolar hyperventilation due to reflex stimulation of irritant receptors.
Increased airway resistance due to constriction of airways distal to the bronchi.
Decreased pulmonary compliance due to lung edema, lung hemorrhage, or loss of surfactant.
Right-Ventricular (RV) Dysfunction
Progressive right heart failure is the usual cause of death from PE. As pulmonary vascular resistance increases, RV wall tension rises and causes further RV dilation and dysfunction. RV contraction continues even after the left ventricle (LV) starts relaxing at end-systole. Consequently, the interventricular septum bulges into and compresses an intrinsically normal left ventricle. Diastolic LV impairment develops, attributable to septal displacement, and results in reduced LV distensibility and impaired LV filling during diastole. Increased RV wall tension also compresses the right coronary ...