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Pulmonary Embolism

If blood flowing within the blood vessels of the body stops, the tissue it supplies could die from lack of oxygen. If, after a serious wound, blood flowing outside the body does not stop, a person could die from hemorrhage. Yet, the blood within the blood vessels flows almost perfectly throughout life, and bleeding usually stops within minutes after a cut. Occasionally, blood can clot within the blood vessels, which is called a thrombus. Abnormal material floating in the blood is called an embolus. A thrombus that breaks free and floats in the moving bloodstream is called a thromboembolism. The blood in the veins, with its slow flow and low pressure, is more likely to clot (venous thrombus) than blood in the arteries; it may go to the lungs (pulmonary embolism or venous thromboembolism), where it can become lodged in the small blood vessels. An embolism can also be caused by other material floating free in the bloodstream, as in, for example, tumor embolism or foreign-body embolism, but these conditions are rare compared to thromboemboli and are not considered further in this chapter. Blood coagulation is highly regulated; a moving stream works to prevent clotting, and stagnant blood promotes clotting. Tissue injury triggers blood clotting, and any defect in the many factors controlling clotting may increase or decrease the chance of blood coagulation. Pulmonary emboli are common, difficult to diagnose, and often deadly.


Pulmonary Embolism

Whom does it affect?

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Epidemiology, prevalence, economic burden, vulnerable populations

Pulmonary embolism is a common complication of hospitalization and contributes to 5 to 10 percent of deaths in hospitalized patients, making it one of the leading causes of preventable hospital deaths (1­4). Despite it being an enormous health problem, the true incidence of pulmonary embolism is uncertain. The diagnosis of venous thrombi and pulmonary emboli can be difficult and requires specialized imaging techniques that are not available in all hospitals or healthcare settings. In the United States, the estimated incidence of diagnosed pulmonary embolism is 71 to 117 per 100,000 person-years (5­7), but the true incidence is likely to be much more than this rate because studies show that for every case of diagnosed, non-fatal pulmonary embolism, there are 2.5 cases of fatal pulmonary embolism diagnosed only after death (8). Other studies have estimated that more than one million people in the United States are affected by pulmonary embolism per year, with 100,000 to 200,000 of these events being fatal (5,9). Over half of all diagnosed cases of pulmonary embolism in the United States occur in patients in hospitals or nursing homes (10). One recent report estimated that more than 12 million patients (31 percent of patients discharged from hospitals in the United States) are at risk of pulmonary embolism (4). Pulmonary embolism has earned the reputation of a silent killer because less than half of patients who die of pulmonary embolism were diagnosed with the problem prior to death (11). Risk factors for venous thrombosis and, therefore, pulmonary embolism, include advanced age, prolonged immobility, surgery, trauma, malignancy, pregnancy, estrogen therapy, congestive heart failure, and inherited or acquired defects in blood coagulation factors. These risks are cumulative, putting most hospitalized patients, who often have a combination of these factors, at greater risk of having a pulmonary embolism. The overall economic burden of pulmonary embolism in the United States is estimated to be over $1.5 billion a year in healthcare costs. Some estimates suggest that pulmonary embolism results in healthcare costs of more than $30,000 per incident (12). Several studies have determined that prevention of pulmonary embolism in hospitalized patients is cost-effective, costing just $3,000 per pulmonary embolism event avoided (13,14).


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Pulmonary Embolism

CASE STUDY A 33-year-old woman was hospitalized for premature labor at 35 weeks of gestation. Labor was successfully stopped, and she was discharged home on strict bed rest. She returned three weeks later in labor. Fetal distress was identified, and an emergency cesarean section resulted in the delivery of a healthy baby. Two days later, the mother reported "crampy" pain in her right leg and was prescribed pain medications. Four days after delivery, she developed sudden shortness of breath and rapid heart rate. A pulmonary embolism was suspected. She was started on the intravenous anticoagulant heparin and underwent a computed tomography (CT) scan with a contrast dye injected into her vein to outline the pulmonary arteries. The resulting images showed a pulmonary embolism, and she was transferred to the intensive care unit. A lower extremity ultrasound found that the source of the embolism was a venous thrombosis in her right thigh. Over the next several days, the patient improved, and she was started on an oral anticoagulation medicine. After a week in the hospital, she returned home, where she recovered fully. Comment This patient's risk factors for pulmonary thromboembolism included immobility, the high levels of estrogens associated with pregnancy, and the tissue injury associated with surgery. Her first symptom was subtle and did not immediately suggest venous thrombosis. Once pulmonary embolism was suspected, prompt lifesaving treatment was begun even before the CT scan confirmed the diagnosis. This patient was fortunate not to suffer from complications of the anticoagulant, and the blood clot in her leg was successfully treated. Complications such as bleeding can occur from anticoagulants. Unresolved blood clots can cause chronic pain and swelling in the extremity where the thrombosis occurred. In the lungs, unresolved blood clots can cause increased blood pressure (pulmonary hypertension) and be associated with serious chronic disease. Happily, this patient fully recovered.


Pulmonary Embolism

What are we learning about this disease?

Pathophysiology, causes, genetics, environment

Chapter 16

The delicate balance between coagulation, anticoagulation, and dissolution of clots (thrombolysis) is carefully regulated; any change in cells or clotting factors can upset this balance. Changes may be genetic or acquired. For instance, increased platelets in the blood and abnormal hemoglobin, such as that produced in sickle cell disease, can cause unwanted clotting. Deficiencies in the body's natural anticoagulants, such as protein C and S, can result in thrombus formation, especially if another risk factor is present. Mutations in the clotting factor V increase clotting risk by decreasing the breakdown of this factor. Mutations in factor V are common (present in 5 percent of the population). Abnormalities in thrombolysis, such as deficiencies in antithrombin III, can also promote clot formation. Anything that reduces blood flow, such as heart failure, narrowing of blood vessels, or immobility, increases the risk for clotting. And almost anything that causes injury, such as cancer, surgery, or trauma, also increases the risk of clot formation.

a nnual number of hospitalized patients considered at risk for venous thromboembolism

d ischarge diagnosis

Heart failure Respiratory failure Pneumonia Cancer Acute myocardial infarction Stroke Trauma Sepsis Arthropathy/spondylopathy Paralysis/coma Total


1,845,319 1,490,183 1,145,469 1,039,359 577,729 507,106 419,831 417,875 279,261 20,287 7,742,419

The risk of pulmonary embolism depends on the amount of tissue injured and lack of mobility. Brain or nerve tissue injury may be more likely to cause clotting than injuries in other tissue (4).


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Pulmonary Embolism

The greatest risk of pulmonary embolism occurs when a clot has formed in the thighs or pelvis. The blood flow from these areas leads directly to the lungs, where a detached clot can lodge in the pulmonary arteries. Clots in the veins of the calves or arms, however, may also be associated with pulmonary embolism.

how is it prevented, treated, and managed?

Prevention, treatment, staying healthy, prognosis

Preventing venous thrombosis is a major method of preventing pulmonary embolism. People should avoid situations where blood clots might form, such as while staying in a fixed seated position for a long duration in a plane or car. Travelers are encouraged to leave the car or walk around the plane every hour or two and to flex and relax their calf muscles to prevent blood stasis in veins. In the hospital setting, there is even greater risk because patients often suffer tissue injury and are immobilized in bed. Hospitalized patients are encouraged to get out of bed as soon as possible. Mechanical compression stockings are applied to regularly squeeze the veins in the calf muscles of patients who are not able to walk. Patients are treated with anticoagulants that inhibit one or more of the clotting factors. Although the potential side effects of these measures include bleeding, they have been shown to prevent thrombosis and save lives. The first step in making a diagnosis is a clinical evaluation that takes into account the risks, symptoms, and signs. Identification of breakdown products of clots in the blood (D-dimers) is a useful biomarker that can further assess the likelihood of a thrombus. An imaging study, usually a chest CT after the injection of a contrast material, outlines the pulmonary arteries and shows a clot if present. Ultrasound of the large veins of the thighs and lower legs may show the presence of clots in these veins. A nuclear medicine lung scan shows areas where no blood flows and is especially good for smaller lung arteries. If the suspicion is very high and the consequences of delayed diagnosis great, anticoagulation may begin even before the tests are done. Most symptomatic patients with a pulmonary embolism require hospitalization and treatment with anticoagulants. Anticoagulation usually begins with intravenous heparin and is followed by an oral anticoagulant, such as warfarin. Anticoagulation therapy may be prescribed for only a few months or lifelong, depending on the circumstances.


Pulmonary Embolism

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Agents that rapidly break down clots are available. This thrombolytic therapy is usually reserved for severely ill patients because it can cause bleeding. Although infrequent, bleeding into the brain could have dire consequences. In some situations, a filter is placed in the main vein (inferior vena cava) leading from the legs to the lungs to stop any thrombi from traveling to the lungs. The prognosis depends on the size of the pulmonary embolism. The effect can be so mild as to go unnoticed or it can result in sudden death. If a patient is promptly treated and has no recurrence, it is likely that full function will be restored. Undetected or inadequately treated pulmonary embolism can result in pulmonary hypertension and long-term respiratory disability.

are we making a difference?

Research past, present, and future

Although the main conditions associated with blood clotting (stasis or slowing of blood flow), hypercoaguability (abnormal clotting factors), and tissue injury were described by the German pathologist Dr. Rudolf Virchow more than 150 years ago, considerable more knowledge on how these affect pulmonary embolism



This computed tomography (CT) image shows a blood clot (arrow) lodged in the main pulmonary artery obstructing the flow of the contrast material in white.


Dean E. Schraufnagel

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Pulmonary Embolism

The small pulmonary artery was plugged by a pulmonary embolus. The body organizes and dissolves, or tries to dissolve, the clot to reestablish blood flow (arrow).

has been gained in recent years. Genetic factors associated with blood coagulation problems are being discovered, and more detailed information on the process of blood clotting continues to be learned. It is possible to screen persons for several genetic coagulation abnormalities, although it is uncertain which patients should have these tests performed. Population screening has not been shown to save enough lives or reduce illness sufficiently to justify the expense in most cases. Research has continued to improve the diagnostic tools, giving better images of the obstructed blood vessels. D-dimer levels appear to be the best of the many diagnostic blood tests studied, although their high sensitivity, which can lead to false positives, is a drawback. D-dimer levels can be elevated in other high-risk situations, such as surgery and certain diseases that cause these products to be found in the blood.

What we need to cure or eliminate pulmonary embolism

Because blood clotting is so important and complex, it is unlikely that pulmonary embolism will ever be eliminated, but progress in diagnosis, prevention, and


Dean E. Schraufnagel

Pulmonary Embolism

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treatment appears to be reducing its burden. Early recognition and better diagnostic tests may further reduce unexpected death and disability, as well as healthcare costs. Considerable clinical research has attempted to identify the best approach to preventing and treating thrombosis. Several newer anticoagulant drugs are gaining applications because they are either safer, easier to administer, or can be used when side effects from the first-line anticoagulants occur.


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1. Sandler DA, Martin JF. Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis? J R Soc Med 1989;82:203­205. 2. Lindblad B, Sternby NH, Bergqvist D. Incidence of venous thromboembolism verified by necropsy over 30 years. BMJ 1991;302:709­711. 3. Alikhan R, Peters F, Wilmott R, Cohen AT. Fatal pulmonary embolism in hospitalised patients: a necropsy review. J Clin Pathol 2004;57:1254­1257. 4. Anderson FA Jr, Zayaruzny M, Heit JA, Fidan D, Cohen AT. Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism. Am J Hematol 2007;82:777­782. 5. Anderson FA Jr, Wheeler HB, Goldberg RJ, Hosmer DW, Patwardhan NA, Jovanovic B, Forcier A, Dalen JE. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991;151:933­938. 6. Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998;158:585­593. 7. Spencer FA, Emery C, Lessard D, Anderson F, Emani S, Aragam J, Becker RC, Goldberg RJ. The Worcester Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med 2006;21:722­727. 8. Nicolaides AN, Breddin HK, Fareed J, Goldhaber S, Haas S, Hull R, Kalodiki E, Myers K, Samama M, Sasahara A, for the Cardiovascular Disease Educational and Research Trust and the International Union of Angiology. Prevention of venous thromboembolism. International Consensus Statement. Guidelines compiled in accordance with the scientific evidence. Int Angiol 2001;20:1­37. 9. Dalen JE, Alpert JS. Natural history of pulmonary embolism. Prog Cardiovasc Dis 1975;17:257­270. 10. Heit JA, O'Fallon WM, Petterson TM, Lohse CM, Silverstein MD, Mohr DN, Melton LJ 3rd. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med 2002;162:1245­1248. 11. Pineda LA, Hathwar VS, Grant BJ. Clinical suspicion of fatal pulmonary embolism. Chest 2001;120:791­795. 12. MacDougall DA, Feliu AL, Boccuzzi SJ, Lin J. Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic syndrome. Am J Health Syst Pharm 2006;63(suppl 6):S5­S15. 13. McGarry LJ, Thompson D, Weinstein MC, Goldhaber SZ. Cost effectiveness of thromboprophylaxis with a low-molecular-weight heparin versus unfractionated heparin in acutely ill medical inpatients. Am J Manag Care 2004;10:632­642. 14. Dobesh PP. Economic burden of venous thromboembolism in hospitalized patients. Pharmacotherapy 2009;29:943­953.


Pulmonary Embolism

Web sites of interest

National Institutes of Health Pulmonary Embolism Pulmonary Embolus American Heart Association Circulation Article on Pulmonary Embolism and Deep Vein Thrombosis Society for Vascular Surgery Pulmonary Embolism Mayo Clinic Pulmonary Embolism

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