16

Pulmonary Embolism
If blood flowing within the blood vessels of the body stops, the tissue it sup-
plies  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 bleed-
ing ­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 mov-
ing 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 thromboembo-
lism), 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.

165

Whitebook_breathing_Ch16.indd 165 6/25/10 12:55:24 PM

 Pulmonary Embolism Chapter 16

Whom does it affect?

Epidemiology, prevalence, economic burden, vulnerable populations

Pulmonary embolism is a common complication of hospitalization and contrib-

utes to 5 to 10 percent of deaths in hospitalized patients, making it one of the
leading causes of preventable hospital deaths (1–4). Despite it being an enor-
mous 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 (5–7), 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 pulmo-
nary 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, preg-
nancy, 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).

166

Whitebook_breathing_Ch16.indd 166 6/25/10 12:55:24 PM

 Chapter 16 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.

167

Whitebook_breathing_Ch16.indd 167 6/25/10 12:55:24 PM

 Pulmonary Embolism Chapter 16

What are we learning about this disease?

Pathophysiology, causes, genetics, environment

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 ves-
sels, 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 n

Heart failure 1,845,319

Respiratory failure 1,490,183

Pneumonia 1,145,469

Cancer 1,039,359

Acute myocardial infarction 577,729

Stroke 507,106

Trauma 419,831

Sepsis 417,875

Arthropathy/spondylopathy 279,261

Paralysis/coma 20,287

Total 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).

168

Whitebook_breathing_Ch16.indd 168 6/25/10 12:55:24 PM

 Chapter 16 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 encour-
aged 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 hospitaliza-
tion 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.

169

Whitebook_breathing_Ch16.indd 169 6/25/10 12:55:24 PM

 Pulmonary Embolism Chapter 16

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

[R] [L]
Dean E. Schraufnagel

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.

170

Whitebook_breathing_Ch16.indd 170 6/25/10 12:55:25 PM

 Chapter 16 Pulmonary Embolism

Dean E. Schraufnagel
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

171

Whitebook_breathing_Ch16.indd 171 6/25/10 12:55:27 PM

 Pulmonary Embolism Chapter 16

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 anticoagu-
lant 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.

172

Whitebook_breathing_Ch16.indd 172 6/25/10 12:55:27 PM

 Chapter 16 Pulmonary Embolism

References
  1. Sandler DA, Martin JF. Autopsy proven pulmonary embolism in hospital patients: are we
detecting enough deep vein thrombosis? J R Soc Med 1989;82:203–205.
  2. Lindblad B, Sternby NH, Bergqvist D. Incidence of venous thromboembolism verified by
necropsy over 30 years. BMJ 1991;302:709–711.
  3. Alikhan R, Peters F, Wilmott R, Cohen AT. Fatal pulmonary embolism in hospitalised
patients: a necropsy review. J Clin Pathol 2004;57:1254–1257.
  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;82:777–782.
  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;151:933–938.
  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;158:585–593.
  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;21:722–727.
  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;20:1–37.
  9. Dalen JE, Alpert JS. Natural history of pulmonary embolism. Prog Cardiovasc Dis
1975;17:257–270.
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;162:1245–1248.
11. Pineda LA, Hathwar VS, Grant BJ. Clinical suspicion of fatal pulmonary embolism. Chest
2001;120:791–795.
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):S5–S15.
13. McGarry LJ, Thompson D, Weinstein MC, Goldhaber SZ. Cost effectiveness of thrombopro-
phylaxis with a low-molecular-weight heparin versus unfractionated heparin in acutely ill
medical inpatients. Am J Manag Care 2004;10:632–642.
14. Dobesh PP. Economic burden of venous thromboembolism in hospitalized patients.
Pharmacotherapy 2009;29:943–953.

173

Whitebook_breathing_Ch16.indd 173 6/25/10 12:55:27 PM

 Pulmonary Embolism Chapter 16

Web sites of interest

National Institutes of Health
Pulmonary Embolism
www.nlm.nih.gov/medlineplus/pulmonaryembolism.html

Pulmonary Embolus
www.nlm.nih.gov/medlineplus/ency/article/000132.htm

American Heart Association

Circulation Article on Pulmonary Embolism and Deep Vein Thrombosis
www.circ.ahajournals.org/cgi/content/full/106/12/1436

Society for Vascular Surgery

Pulmonary Embolism
www.vascularweb.org/patients/NorthPoint/Pulmonary_Embolism.html

Mayo Clinic
Pulmonary Embolism
www.mayoclinic.com/health/pulmonary-embolism/DS00429

174

Whitebook_breathing_Ch16.indd 174 6/25/10 12:55:27 PM