Pulmonary embolism: an
Torrey A. Laack, MDa,b,c,d,*, Deepi G. Goyal, MDb,c
aDepartment of Pediatric and Adolescent Medicine, Mayo Medical School,
Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
bDepartment of Emergency Medicine, Mayo Medical School, Mayo Clinic,
200 First Street SW, Rochester, MN 55905, USA
cMayo Emergency Medicine Residency, Mayo Medical School, Mayo Clinic,
200 First Street SW, Rochester, MN 55905, USA
dDepartment of Pediatrics, Mayo Medical School, Mayo Clinic,
200 First Street SW, Rochester, MN 55905, USA
The accurate diagnosis of pulmonary embolism (PE) is crucial. PE is
currently the third leading cause of death in the United States with 50,000
to 100,000 estimated deaths per year and an incidence of 0.5 to 1 per 1000
[1–4]. PE is a leading cause of unexpected deaths in hospitalized patients and
a major source of medical malpractice lawsuits . However, the diagnosis is
missed more often than it is made. One author conservatively estimates that
more than half of fatal PE cases are not even suspected antemortem .
Prior autopsy studies consistently have shown the rate to be even higher, at
approximately 70% [7–11]. Conversely, in patients in whom the diagnosis is
considered, the prevalence of PE is only 25% to 35% [12,13]. Therefore,
clinicians generally miss PE when it is present and suspect it when it is not.
PE is truly an unsuspected killer with profound clinical implications.
Although patients in whom PE is diagnosed and treated have a mortality
rate of only 3% to 8% [3,14,15], those in whom the diagnosis is missed have
a fourfold to sixfold greater mortality [3,6,15].
Before the use of heparin, surgical interventions were the only treatment
options available for PE with a mortality rate approaching 100% .
Heparin first was administered to treat PE in the 1930s, but concerns over its
safety in this setting prevented more widespread use. It was not until 1960
that the benefits of anticoagulation therapy were confirmed . Beginning
* Corresponding author. Department of Emergency Medicine, Mayo Medical School,
Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
E-mail address: firstname.lastname@example.org (T.A. Laack).
0733-8627/04/$ - see front matter ? 2004 Elsevier Inc. All rights reserved.
Emerg Med Clin N Am
22 (2004) 961–983
in the 1960s, the use of fibrinolytics was studied; fibrinolytics were reserved
primarily for unstable patients with PE . With the advent of effective
therapy, the accurate diagnosis of thromboembolic disease became vital.
Although many deaths are attributed to undiagnosed pulmonary emboli,
the actual incidence of PE in the general population and the risk of
mortality or morbidity from an individual pulmonary embolus are un-
known. A high incidence of asymptomatic PE has been shown in patients
with deep venous thrombosis (DVT) [18–22], suggesting that PE may be
common and only infrequently may lead to death. Although some studies
have found mortality rates from untreated PE ranging from 25% to 30%,
these studies involved patients with other comorbidities that likely
contributed to the adverse outcomes [17,23,24].Other studies involving pa-
tients without coexisting cardiopulmonary disease have found that mortality
even with untreated or recurrent PE was significantly lower [22,24–27].
A follow-up study of the untreated patients with PE from the Prospective
Investigation of Pulmonary Embolism Diagnosis (PIOPED) revealed
a mortality rate from PE of only 5% (1 in 20) .
Given the fact that anticoagulation carries with it significant bleeding
risks and that not all cases of PE cause morbidity or mortality, the risk of
misdiagnosis of PE is not limited to missing the diagnosis. Incorrectly diag-
nosing PE in patients in whom it is absent or inconsequential unnecessarily
exposes them to the risks inherent with long-term anticoagulation therapy.
Because the accurate diagnosis of PE is crucial to maximizing patient
outcomes, this article focuses on atypical presentations, unique challenges in
certain patient populations, and current diagnostic strategies for PE.
Venous thromboembolism (VTE) is a disease with a spectrum of mani-
festations that include thrombophlebitis, DVT, and PE. Most pulmonary
emboli have their origin in clots in the iliac, deep femoral, or popliteal veins.
Pulmonary emboli also can originate from sources in the upper extremities,
central vascular access devices, heart, and vena caval filters [28–30]. The site
of the DVT does not seem to be as important as previously was thought
because PE can occur from any site of DVT formation . Calf vein
thrombosis, previously considered relatively benign, propagates above the
knee in approximately 80% and may cause PE without first extending
proximally . Likewise, although superficial thrombophlebitis is generally
benign, it can extend into the deep venous system and pose a risk for PE
. In many instances of PE, no peripheral source of thrombosis is ever
Virchow first described the process of thrombosis as involving a triad of
stasis, hypercoagulability, and endothelial injury . Risk factors for PE
can be inherited or acquired (Box 1) and must be considered when
assessing a patient’s probability of PE [29,30,35]. The strongest risk factor of
962 T.A. Laack, D.G. Goyal / Emerg Med Clin N Am 22 (2004) 961–983
VTE seems to be a history of prior thromboembolic disease . In
addition, malignancy and surgery are well known to be associated with
VTE. Certain malignancies, such as tumors affecting the lung, brain,
ovaries, and pancreas, are especially prone toward predisposing patients to
VTE , as are neurosurgical and orthopedic surgical procedures .
Major trauma patients are a high-risk patient population that deserves
particular attention because PE is the third most common cause of death in
these patients [2,36]. One study of victims of major trauma revealed that
nearly 60% had a DVT, most of whom were asymptomatic .
Despite the clinical significance of risk factors for VTE, Morgenthaler
and Ryu  found that 12% (11 of 92) of patients with PE as the cause of
death at autopsy lacked any known risk factor. Risk factors must be taken
into account in conjunction with the patient’s history and presentation, but
an absence of risk factors does not reliably exclude the diagnosis of PE.
The presentation of PE is occasionally dramatic, but more commonly
patients present with subtle clinical findings, or they may be completely
Box 1. Risk factors predisposing to venous thromboembolism
Inherited risk factors
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
Factor V Leiden mutation
Acquired risk factors
Prior history of venous thromboembolism
Central venous access devices
Pregnancy and the puerperium
Immobilization (travel, paralysis, bedridden state)
Congestive heart failure
Oral contraceptives/hormone replacement therapy
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asymptomatic. This situation contributes to the large number of cases that
are missed on initial presentation. The classic findings of hemoptysis,
dyspnea, and chest pain are insensitive and nonspecific for a diagnosis of
PE, with fewer than 20% having this classic triad. The incidence of common
symptoms in patients suspected of having PE is depicted in Table 1 . One
prospective observational study found that the single historical finding most
sensitive for PE was unexplained dyspnea. Even this finding was absent,
however, in 8% of the patients studied . Although unexplained chest
pain or dyspnea always should lead to the consideration of PE, the fact that
presentations of PE are often subtle mandates that the clinician not over-
look the diagnosis based on a lack of these symptoms.
No single physical examination finding is sensitive or specific for PE.
Table 1 shows the prevalence of various signs in patients suspected of having
PE . Although other studies reveal tachypnea to be the most sensitive
clinical sign, it is absent in 5% to 13% of cases of PE [34,40]. Tachycardia is
even less sensitive, especially in younger patients, with 70% of PE patients
younger than 40 years old and 30% of patients older than 40 having heart
rates less than 100 beats/min . Fever tends to be low grade, and its
presence may mislead the clinician into suspecting an infectious etiology.
Symptoms and signs in 500 patients with clinically suspected pulmonary embolism
PE present n=202 PE absent n = 298
Dyspnea (sudden onset)
Dyspnea (gradual onset)
Chest pain (pleuritic)
Chest pain (substernal)
Hypotension \90 mm Hg
Neck vein distention
Leg swelling (unilateral)
Pleural friction rub
Abbreviation: PE, pulmonary embolism.
From Miniati M, Prediletto R, Fromichi B, et al. Accuracy of clinical assessment in the
diagnosis of pulmonary embolism. Am J Respir Crit Care Med 1999;159:866; with permission.
964T.A. Laack, D.G. Goyal / Emerg Med Clin N Am 22 (2004) 961–983
Stein et al  found fever with no other source present in 14% of patients
Data from the PIOPED found that in patients diagnosed with PE, 97%
had the presence of dyspnea, chest pain, or tachypnea . Dyspnea, chest
pain, and tachypnea are all nonspecific symptoms, however, that are found
more commonly with diseases other than PE. This finding is likely subject to
considerable selection bias because only patients in whom the diagnosis was
suspected were enrolled in the PIOPED study, whereas patients with silent
or atypical presentations of PE would have been missed and their symptoms
not recorded. The symptoms of dyspnea, pleuritic chest pain, and tachypnea
are not only nonspecific, but also they may be insensitive when generalized
to all patients with PE .
Patients traditionally have been described as having one of three classic
syndromes: pulmonary infarction, isolated dyspnea, or circulatory collapse.
This is an oversimplification of the clinical presentation of PE that does not
account for atypical presentations and occult pulmonary emboli. Patients in
whom the diagnosis is suspected tend to present, however, with one of these
three syndromes. Although one should not limit clinical suspicion only to
patients in these categories, it is extremely difficult to diagnose PE reliably in
patients outside of this simplified scheme.
Patients with pulmonary infarction commonly present with chest pain
secondary to irritation of the pleura. It may be difficult to differentiate
between PE and pneumonitis or pleuritis. Hemoptysis usually is self-limited
and occurs in approximately one third of these patients. Pulmonary infarc-
tion is much more common in older patients with underlying cardiopul-
monary disease, and they tend to present with pleuritic chest pain more
frequently [30,42]. PE may be present in 20% of young patients, however,
without specific risk factors for VTE who present with a complaint of
pleuritic chest pain . Pulmonary infarct is associated with submassive
and less severe PE than isolated dyspnea or circulatory collapse [42,43].
In patients with isolated dyspnea, the severity of symptoms is related to
the degree of vascular obstruction and their underlying cardiopulmonary
reserve. Even with obstruction of 50%, patients may remain asymptomatic
. PE may be difficult to distinguish from other causes of dyspnea, such as
congestive heart failure (CHF), hyperventilation, reactive airway disease, or
obstructive lung disease. Patients with circulatory collapse have the most
severe form of PE. They may present with syncope, hemodynamic in-
stability, or full cardiopulmonary arrest.
Atypical presentations of PE are common, with symptoms such as
abdominal pain, back pain, fever, cough, atrial fibrillation, and hiccoughs
. As noted earlier, most fatal pulmonary emboli are never suspected and
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