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Overview of acute pulmonary embolism in adults

Authors: B Taylor Thompson, MD, Christopher Kabrhel, MD, MPH
Section Editor: Jess Mandel, MD
Deputy Editor: Geraldine Finlay, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2019. | This topic last updated: Aug 21, 2018.

INTRODUCTION

Acute pulmonary embolism (PE) is a form of venous thromboembolism (VTE) that is common and
sometimes fatal. The clinical presentation of PE is variable and often nonspecific making the diagnosis
challenging. The evaluation of patients with suspected PE should be efficient so that patients can be
diagnosed and therapy administered quickly to reduce the associated morbidity and mortality.

The definition, epidemiology, pathogenesis, and pathophysiology of PE are discussed in detail in this
topic. A broad overview of the clinical presentation, evaluation, and diagnosis as well as treatment,
prognosis, and follow-up of PE is also provided in this topic; however, a detailed discussion of these
issues is provided separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant
adult with suspected acute pulmonary embolism" and "Treatment, prognosis, and follow-up of acute
pulmonary embolism in adults".)

DEFINITION AND NOMENCLATURE

Definition — Pulmonary embolus (PE) refers to obstruction of the pulmonary artery or one of its branches
by material (eg, thrombus, tumor, air, or fat) that originated elsewhere in the body. This topic review
focuses upon PE due to thrombus. Tumor, air, and fat emboli are discussed separately. (See "Pulmonary
tumor embolism and lymphangitic carcinomatosis in adults: Diagnostic evaluation and management" and
"Air embolism" and "Fat embolism syndrome".)

Nomenclature — PE can be classified by the following:

● The temporal pattern of presentation (acute, subacute, or chronic) – Patients with PE can present
acutely, subacutely, or chronically:

• Acute – Patients with acute PE typically develop symptoms and signs immediately after
obstruction of pulmonary vessels.

• Subacute – Some patients with PE may also present subacutely within days or weeks following
the initial event.

• Chronic – Patients with chronic PE slowly develop symptoms of pulmonary hypertension over
many years (ie, chronic thromboembolic pulmonary hypertension; CTEPH).

An overview of acute and subacute PE is discussed in this review. The etiology, clinical
manifestations, diagnosis, and treatment of CTEPH are discussed separately. (See "Clinical
manifestations and diagnosis of chronic thromboembolic pulmonary hypertension" and "Overview of
the treatment of chronic thromboembolic pulmonary hypertension".)

● The presence or absence of hemodynamic stability (hemodynamically unstable or stable) –

Hemodynamically unstable PE is also called "massive" or "high-risk" PE. Hemodynamically stable PE
is called "submassive" or "intermediate-risk" PE if there is associated right ventricular strain, or "low-
risk" PE if there is no evidence of right ventricular strain. Hemodynamically stable and unstable PE
are defined as the following:

• Hemodynamically unstable PE is that which results in hypotension. Hypotension is defined as a

systolic blood pressure <90 mmHg or a drop in systolic blood pressure of ≥40 mmHg from
baseline for a period >15 minutes or hypotension that requires vasopressors or inotropic support
and is not explained by other causes such as sepsis, arrhythmia, left ventricular dysfunction
from acute myocardial ischemia or infarction, or hypovolemia. Although hemodynamically
unstable PE is often caused by large (ie, massive) PE, it can sometimes be due to small PE in
patients with underlying cardiopulmonary disease. Thus, the term "massive" PE does not
necessarily describe the size of the PE as much as its hemodynamic effect. (See
'Pathophysiologic response to PE' below.)

• Hemodynamically stable PE is defined as PE that does not meet the definition of

hemodynamically unstable PE. There is a spectrum of severity within this population ranging
from patients who present with small, mildly symptomatic or asymptomatic PE (also known as
"low-risk PE") to those who present with mild or borderline hypotension that stabilizes in
response to fluid therapy, or those who present with right ventricle dysfunction (also known as
"submassive" or "intermediate-risk" PE). (See "Thrombolytic (fibrinolytic) therapy in acute
pulmonary embolism and lower extremity deep vein thrombosis", section on 'Hemodynamically
stable patients'.)

The distinction between hemodynamically stable and unstable PE is important because patients with
hemodynamically unstable PE are more likely to die from obstructive shock (ie, severe right
ventricular failure). Importantly, death from hemodynamically unstable PE often occurs within the
first two hours, and the risk remains elevated for up to 72 hours after presentation [1,2]. (See "Clinical
 presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary
embolism", section on 'Hemodynamically unstable patients' and "Treatment, prognosis, and follow-up
of acute pulmonary embolism in adults", section on 'Prognosis' and "Thrombolytic (fibrinolytic)
therapy in acute pulmonary embolism and lower extremity deep vein thrombosis".)

● The anatomic location (saddle, lobar, segmental, subsegmental) – Saddle PE lodges at the
bifurcation of the main pulmonary artery, often extending into the right and left main pulmonary
arteries. Approximately 3 to 6 percent of patients with PE present with a saddle embolus [3,4].
Traditionally, saddle PE was thought to be associated with hemodynamic instability and death.
However, retrospective studies suggest that among those diagnosed with a saddle embolus, only 22
percent are hemodynamically unstable, with an associated mortality of 5 percent [3,4]. Clot that is "in
transit" through the heart is often classified as a form of PE, even though the thrombus has not yet
lodged in a pulmonary artery. Clot-in-transit is associated with high mortality (up to 40 percent).

Most PE move beyond the bifurcation of the main pulmonary artery to lodge distally in the main lobar,
segmental, or subsegmental branches of a pulmonary artery. PE can be bilateral or unilateral,
depending on whether they obstruct arteries in the right, left, or both lungs. Smaller thrombi that are
located in the peripheral segmental or subsegmental branches are more likely to cause pulmonary
infarction and pleuritis (image 1). (See 'Pathophysiologic response to PE' below.)

● The presence or absence of symptoms (symptomatic or asymptomatic) – Symptomatic PE refers to

the presence of symptoms that usually leads to the radiologic confirmation of PE, whereas
asymptomatic PE refers to the incidental finding of PE on imaging (eg, contrast-enhanced computed
tomography performed for another reason) in a patient without symptoms. (See "Clinical
presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary
embolism", section on 'Diagnosis'.)

EPIDEMIOLOGY

General population — Estimates of the incidence of pulmonary embolism (PE) in the general population
have increased following the introduction of D-dimer testing and computed tomographic pulmonary
angiography in the 1990s [5-10]. One database analysis reported a doubling in the incidence of PE from
62 cases per 100,000 in the five year period before 1998 to 112 cases per 100,000 in the seven years after
1998 [5]. Other studies have confirmed similar increased rates over time [11]. In contrast, a Canadian
database reported an incidence rate of PE as 0.38 per 1000 person years, a rate that appeared to be
stable between 2002 and 2012 [10].

The overall incidence is higher in males compared with females (56 versus 48 per 100,000, respectively)
[12-14]. The incidence rises with increasing age, particularly in women, such that PE has an incidence of
>500 per 100,000 after the age of 75 years [13,15]. The use of statins may reduce the incidence of PE
[16].

In the United States, PE accounts for approximately 100,000 annual deaths [12,17]. In Europe, PE
accounts for 300,000 deaths annually [18]. In an analysis based upon data from five European countries,
the majority of VTE-related deaths were due to hospital-acquired PE and most were diagnosed
antemortem [19]. However, many causes of sudden cardiac death are thought to be secondary to PE, so
the actual mortality attributable to PE is difficult to estimate.

Deaths from diagnosed PE have been declining [8,12,20], with one study reporting deaths from PE that
decreased between 1979-1998, from 191 to 94 per million [12]. In another study, the mortality risk ratio
from PE declined from 138 (95% CI, 125-153) in 1980-1989 to 36.08 (95% CI, 32.65-39.87) in 2000-2011
[21].

Overall mortality from PE appears to be high. Another study reported a 30-day and 1 year mortality at 4
and 13 percent, respectively and a case-fatality rate that increased with increasing age [10].

Age-adjusted mortality rates for African-American adults have been reported to be 50 percent higher than
those for whites; in turn, mortality rates for whites are 50 percent higher than those for other races (Asian,
American Indian, etc) [12].

Special populations — The incidence of venous thromboembolism (DVT and PE) in select populations is
discussed in the following sections:

● Patients with malignancy (see "Risk and prevention of venous thromboembolism in adults with
cancer", section on 'Incidence and risk factors' and "Supportive care of the patient with locally
advanced or metastatic exocrine pancreatic cancer", section on 'Venous thromboembolism' and
"Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and
pulmonary embolism) in adult patients with malignancy", section on 'Recurrence risk')

● Patients who are pregnant (see "Pulmonary embolism in pregnancy: Epidemiology, pathogenesis, and
diagnosis", section on 'Epidemiology')

● Patients with stroke (see "Prevention and treatment of venous thromboembolism in patients with
acute stroke")

● Hospitalized medical patients (see "Prevention of venous thromboembolic disease in acutely ill
hospitalized medical adults", section on 'General medical patients')

● Hospitalized surgical patients (see "Prevention of venous thromboembolic disease in adult

nonorthopedic surgical patients")

● Hospitalized gynecologic patients (see "Risk and prevention of venous thromboembolism in adults
with cancer", section on 'Incidence and risk factors')

● Patients with nephrotic syndrome (see "Hypercoagulability in nephrotic syndrome", section on

'Epidemiology')

● Patients with acute traumatic spinal cord injury (see "Acute traumatic spinal cord injury", section on
'Venous thromboembolism and pulmonary embolism')

● Patients with total joint arthroplasty or replacement (see "Complications of total knee arthroplasty",
section on 'Thromboembolism' and "Total joint replacement for severe rheumatoid arthritis", section
 on 'Thromboembolism' and "Complications of total hip arthroplasty", section on 'Venous
thromboembolism')

● Patients with inherited thrombotic disorders (see "Overview of the causes of venous thrombosis",
section on 'Inherited thrombophilia')

PATHOGENESIS AND PATHOPHYSIOLOGY

Pathogenesis — The pathogenesis of pulmonary embolism (PE) is similar to that which underlies the
generation of thrombus (ie, Virchow's triad). Virchow's triad consists of venous stasis, endothelial injury,
and a hypercoagulable state, which is discussed separately. (See "Overview of the causes of venous
thrombosis", section on 'Virchow's triad'.)

Risk factors — The few studies that have specifically examined risk factors for PE alone confirm that they
are similar to those for venous thromboembolism (VTE) in general [22-28]. Risk factors can be classified
as inherited (ie, genetic) and acquired. Twenty to thirty genetic risk factors for VTE have been identified,
including factor V Leiden and the prothrombin gene mutation (20210-A) [29,30]. Acquired risk factors can
be further sub-classified as provoking (eg, recent surgery, trauma, immobilization, initiation of hormone
therapy, active cancer) or non-provoking (eg, obesity, heavy cigarette smoking) [28]. Risk factors for VTE
are discussed in detail separately.(See "Overview of the causes of venous thrombosis".)  

Source — Most emboli are thought to arise from lower extremity proximal veins (iliac, femoral, and
popliteal) (table 1) and more than 50 percent of patients with proximal vein deep venous thrombosis
(DVT) have concurrent PE at presentation [31-35]. Calf vein DVT rarely embolizes to the lung and two–
thirds of calf vein thrombi resolve spontaneously after detection [36-45]. However, if untreated, one-third
of calf vein DVT extend into the proximal veins, where they have greater potential to embolize. PE can
also arise from DVT in non-lower-extremity veins including renal and upper extremity veins, although
embolization from these veins is less common. (See "Overview of the treatment of lower extremity deep
vein thrombosis (DVT)", section on 'Distal DVT'.)

Most thrombi develop at sites of decreased flow in the lower extremity veins, such as valve cusps or
bifurcations. However, they may also originate in veins with higher venous flow including the inferior vena
cava, or the pelvic veins, and in non-lower-extremity veins including renal and upper extremity veins. (See
"Hypercoagulability in nephrotic syndrome".)

Pathophysiologic response to PE — Pulmonary emboli are typically multiple, with the lower lobes being
involved in the majority of cases [46]. Once thrombus lodges in the lung, a series of pathophysiologic
responses can occur:

● Infarction – In about 10 percent of patients, small thrombi lodge distally in to the segmental and
subsegmental vessels resulting in pulmonary infarction [47]. These patients are more likely to have
pleuritic chest pain and hemoptysis, presumed to be due to an intense inflammatory response in the
lung and adjacent visceral and parietal pleura.
 ● Abnormal gas exchange – Impaired gas exchange from PE is due to mechanical and functional
obstruction of the vascular bed altering the ventilation to perfusion ratio, and also to inflammation
resulting in surfactant dysfunction and atelectasis resulting in functional intrapulmonary shunting.
Both mechanisms cause hypoxemia [48]. Inflammation is also thought to be responsible for
stimulating respiratory drive resulting in hypocapnia and respiratory alkalosis. Hypercapnia and
acidosis are unusual in PE unless shock is present. (See "Clinical presentation, evaluation, and
diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on
'Laboratory tests' and "Oxygenation and mechanisms of hypoxemia".)

● Cardiovascular compromise – Hypotension from PE is due to diminished stroke volume and cardiac
output. In patients with PE, pulmonary vascular resistance (PVR) is increased due to physical
obstruction of the vascular bed with thrombus and hypoxic vasoconstriction within the pulmonary
arterial system. Increased PVR, in turn, impedes right ventricular outflow and causes right ventricular
dilation and flattening or bowing of the intraventricular septum. Both diminished flow from the right
ventricle and right ventricular dilation reduce left ventricular preload thereby compromising cardiac
output.

As an example, when obstruction of the pulmonary vascular bed approaches 75 percent, the right
ventricle must generate a systolic pressure in excess of 50 mmHg to preserve adequate pulmonary
artery flow [49]. When the right ventricle is unable to accomplish this, it fails and hypotension ensues.
Thus, in patients without underlying cardiopulmonary disease, multiple large thrombi are generally
responsible for hypotension via this mechanism. In contrast, in patients with underlying
cardiopulmonary disease, hypotension can be induced by smaller emboli, likely due to a substantial
vasoconstrictive response and/or an inability of the right ventricle to generate sufficient pressure to
combat high PVR.

CLINICAL PRESENTATION, EVALUATION, AND DIAGNOSIS

Clinical presentation — Pulmonary embolism (PE) has a wide variety of presenting features, ranging from
no symptoms to shock or sudden death. The most common presenting symptom is dyspnea followed by
chest pain (classically pleuritic in nature), cough, and symptoms of deep venous thrombosis. Hemoptysis
is an unusual presenting symptom. Rarely do patients present with shock, arrhythmia, or syncope. Many
patients, including some with large PE, are asymptomatic or have mild or nonspecific symptoms. Thus, it
is critical that a high level of suspicion be maintained such that clinically relevant cases are not missed.
The signs and symptoms of PE are discussed in detail separately. (See "Clinical presentation, evaluation,
and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Clinical
presentation'.)

Diagnostic approach to patients with suspected PE — For most patients with suspected PE who are
hemodynamically stable, we suggest an approach which combines clinical and pretest probability
assessment (calculator 1) (table 2), D-dimer testing, and definitive diagnostic imaging (algorithm 1 and
algorithm 2 and algorithm 3). Definitive imaging includes computed tomographic pulmonary angiography
and less commonly, ventilation perfusion scanning or other imaging modalities. For patients who are
hemodynamically unstable and in whom definitive imaging is unsafe, bedside echocardiography or
venous compression ultrasound may be used to obtain a presumptive diagnosis of PE to justify the
administration of potentially life-saving therapies.

Details regarding the evaluation and diagnostic approach to patients with suspected PE are discussed
separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected
acute pulmonary embolism".)

TREATMENT

When a patient presents with suspected acute pulmonary embolism (PE), initial resuscitative therapy
should focus upon oxygenating and stabilizing the patient. Resuscitative therapy may range from
supplemental oxygen to ventilatory support, hemodynamic support. An overview of the general measures
used to resuscitate patients with suspected PE is discussed in detail separately. (See "Treatment,
prognosis, and follow-up of acute pulmonary embolism in adults".)

Once the diagnosis is made, the mainstay of therapy for patients with confirmed PE is anticoagulation,
depending upon the risk of bleeding. When the pre-test probability of PE is high or diagnostic imaging will
be delayed, anticoagulation is sometimes started before a diagnosis of PE is confirmed. Data that
support initial, long-term, and indefinite anticoagulation, and factors that determine whether or not a
patient can be treated in the outpatient setting, are discussed separately. (See "Rationale and indications
for indefinite anticoagulation in patients with venous thromboembolism" and "Treatment, prognosis, and
follow-up of acute pulmonary embolism in adults", section on 'Outpatient anticoagulation' and "Venous
thromboembolism: Initiation of anticoagulation (first 10 days)".)

Patients with life-threatening PE may require additional treatment beyond anticoagulation, including
thrombolysis, inferior vena cava filters, and embolectomy. Select populations that require specific
anticoagulation or alternative treatment strategies include:

● Patients with malignancy (see "Anticoagulation therapy for venous thromboembolism (lower
extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy")

● Patients who are pregnant (see "Deep vein thrombosis and pulmonary embolism in pregnancy:
Treatment" and "Use of anticoagulants during pregnancy and postpartum")

● Patients with heparin-induced thrombocytopenia (see "Clinical presentation and diagnosis of

heparin-induced thrombocytopenia" and "Management of heparin-induced thrombocytopenia")

● Patients with a contraindication to anticoagulation (inferior vena cava filter placement) (see
"Overview of the treatment of lower extremity deep vein thrombosis (DVT)", section on 'Inferior vena
cava filter' and "Placement of vena cava filters and their complications")

● Patients who are hemodynamically unstable or fail anticoagulation (thrombolytic therapy and/or
embolectomy) (see "Thrombolytic (fibrinolytic) therapy in acute pulmonary embolism and lower
extremity deep vein thrombosis" and "Treatment, prognosis, and follow-up of acute pulmonary
embolism in adults", section on 'Embolectomy')
PROGNOSIS

The major adverse outcomes associated with pulmonary embolism (PE) include the following:

● Recurrent thromboembolism – The recurrence rate depends upon factors including adequate
therapeutic anticoagulation and the clinical nature of the embolic event (eg, provoked, unprovoked),
the details of which are discussed separately. (See "Rationale and indications for indefinite
anticoagulation in patients with venous thromboembolism", section on 'Assessing the risk of
recurrence'.)

● Chronic thromboembolic pulmonary hypertension (CTEPH) – CTEPH is an uncommon (1 to 4

percent) late outcome of patients with PE. The prognosis of patients with CTEPH is discussed
separately. (See "Overview of the treatment of chronic thromboembolic pulmonary hypertension".)  

● Death – PE left untreated, is associated with an overall mortality of up to 30 percent. Mortality is

significantly reduced with anticoagulation. Most deaths attributable to PE occur during the first week
following diagnosis (early mortality) and are due to recurrent venous thromboembolism and shock.
However, many deaths following PE are due to predisposing comorbidities or are multifactorial. One
study demonstrated increased risk of death for up to eight years in patients without comorbidities
[50], while other studies have reported that mortality remains increased for as long as 30 years (long-
term mortality) with death mostly due to predisposing comorbidities (eg, cardiovascular disease,
malignancy, sepsis) [21]. Details regarding the mortality of patients diagnosed with PE are discussed
separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults",
section on 'Morbidity and mortality'.)

Prognostic models that incorporate clinical findings with or without laboratory tests can predict death
and/or recurrence. Among prognostic models, the Pulmonary Embolism Severity Index (PESI) and the
simplified PESI (sPESI) are the most well known (table 3) and predict all-cause mortality after PE. A
detailed discussion of the prognostic value of these and other models is presented separately. (See
"Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Prognostic
factors' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on
'Prognostic models'.)

MONITORING AND FOLLOWUP

Patients with pulmonary embolism (PE) should be monitored for the following:

● Laboratory evidence of therapeutic efficacy in patients receiving unfractionated heparin and/or

warfarin. (See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Warfarin
administration' and "Direct oral anticoagulants and parenteral direct thrombin inhibitors: Dosing and
adverse effects" and "Heparin and LMW heparin: Dosing and adverse effects", section on 'Laboratory
monitoring and dose titration (unfractionated heparin)'.)
 ● Early complications of PE, predominantly recurrent thromboembolism and progression of the
diagnosed PE. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with
suspected acute pulmonary embolism", section on 'Clinical presentation'.) Patients with confirmed
recurrent PE while on therapy should be evaluated for sub-therapeutic anticoagulation or, if
anticoagulation is adequate, other causes of recurrence. Investigating and managing the early
complications of PE, including recurrence, are discussed separately. (See "Treatment, prognosis, and
follow-up of acute pulmonary embolism in adults", section on 'Monitoring and follow-up' and
"Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on
'Management of recurrence on therapy'.)

● Late complications of PE, mostly, chronic thromboembolic pulmonary hypertension CTEPH. Most
patients who develop CTEPH do so in the first two years following PE and the diagnosis is usually
suspected clinically because of persistent symptoms. The clinical presentation and diagnosis of
CTEPH are discussed separately. (See "Clinical manifestations and diagnosis of chronic
thromboembolic pulmonary hypertension".)

● Complications of therapy for PE, including bleeding and adverse effects of medication or devices.
(See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Complications' and "Direct
oral anticoagulants and parenteral direct thrombin inhibitors: Dosing and adverse effects" and
"Placement of vena cava filters and their complications", section on 'Complications' and "Treatment,
prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Embolectomy' and
"Heparin and LMW heparin: Dosing and adverse effects", section on 'Other complications' and
"Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Mitigating
bleeding risk' and "Risks and prevention of bleeding with oral anticoagulants" and "Thrombolytic
(fibrinolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis".)

● The risk of recurrence and bleeding. The risk of recurrence and bleeding should be periodically
assessed during therapy and, again, at the end of therapy to assess the need for indefinite
anticoagulation. Assessing recurrence and bleeding risk as well as indications for indefinite
anticoagulation are discussed separately. (See "Rationale and indications for indefinite
anticoagulation in patients with venous thromboembolism", section on 'Making the decision to
indefinitely anticoagulate'.)

● The need for device removal. Patients who had an inferior vena cava filter placed because
anticoagulation was contraindicated should, once the contraindication has resolved, initiate
anticoagulant therapy and have the filter retrieved, if feasible. (See "Placement of vena cava filters
and their complications", section on 'Filter retrieval'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around the
world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein
thrombosis, and pulmonary embolism".)
INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The
Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they
answer the four or five key questions a patient might have about a given condition. These articles are best
for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These articles are written at
the 10th to 12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail
these topics to your patients. (You can also locate patient education articles on a variety of subjects by
searching on "patient info" and the keyword(s) of interest.)

● Basics topics (see "Patient education: Pulmonary embolism (blood clot in the lungs) (The Basics)")

● Beyond the Basics topics (see "Patient education: Pulmonary embolism (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Pulmonary embolism (PE) is a common and sometimes fatal disease. It is due to obstruction of a
pulmonary artery or one of its branches by material (eg, thrombus, tumor, air, or fat) that originated
elsewhere in the body. (See 'Definition' above.)

● PE can be classified according to the presence or absence of hemodynamic stability

(hemodynamically unstable or stable), the temporal pattern of presentation (acute, subacute, or
chronic), the anatomic location (saddle, lobar, segmental, subsegmental), and the presence or
absence of symptoms (symptomatic or asymptomatic). Patients with hemodynamically unstable PE,
defined as a systolic blood pressure <90 mmHg or a drop in systolic blood pressure of ≥40 mmHg
from baseline for >15 minutes, should be distinguished from patients with hemodynamically stable
PE because they are more likely to die from obstructive shock in the first two hours of presentation
and may therefore benefit from more aggressive treatment. (See 'Nomenclature' above.)

● The overall incidence of PE is approximately 112 cases per 100,000. PE is slightly more common in
males than females and incidence increases with age. Deaths from PE account for approximately
100,000 deaths per year in the United States. (See 'Epidemiology' above.)

● The pathogenesis of PE is similar to that of deep venous thrombosis. Most emboli arise from lower
extremity proximal veins (iliac, femoral, and popliteal) (table 1). However, they may also originate in
right heart, inferior vena cava or the pelvic veins, and in the renal and upper extremity veins. (See
"Overview of the causes of venous thrombosis" and 'Pathogenesis and pathophysiology' above.)

● PE has a wide variety of presenting features, ranging from no symptoms to shock or sudden death.
The most common presenting symptom is dyspnea followed by chest pain, cough, and symptoms of
deep venous thrombosis. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant
 adult with suspected acute pulmonary embolism" and 'Clinical presentation, evaluation, and
diagnosis' above.)

For most patients with suspected PE we suggest an approach which combines clinical and pretest
probability assessment (calculator 1) (table 2), D-dimer testing, and definitive diagnostic imaging,
usually computed tomographic pulmonary angiography and, less commonly, ventilation perfusion
scanning (algorithm 1 and algorithm 2 and algorithm 3). (See "Clinical presentation, evaluation, and
diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and 'Diagnostic
approach to patients with suspected PE' above.)

● Initial resuscitative therapy for patients with suspected PE should focus upon oxygenating and
stabilizing the patient. Once the diagnosis is made, the mainstay of therapy for patients with
confirmed PE is anticoagulation, depending upon the risk of bleeding. Alternative treatments include
thrombolysis, inferior vena cava filters, and embolectomy. (See "Treatment, prognosis, and follow-up
of acute pulmonary embolism in adults" and 'Treatment' above.)

● PE can be complicated by recurrent thrombosis, chronic thromboembolic pulmonary hypertension

(CTEPH), and death. PE left untreated, has an overall mortality of up to 30 percent, which is
significantly reduced with anticoagulation. Prognostic models that incorporate clinical findings (eg,
Pulmonary Embolism Severity Index [PESI] and the simplified PESI [sPESI] (table 3)) with or without
laboratory tests can predict death and/or recurrence. (See "Treatment, prognosis, and follow-up of
acute pulmonary embolism in adults", section on 'Prognosis' and 'Prognosis' above.)

● Patients treated with unfractionated heparin and/or warfarin should be monitored for laboratory
evidence of therapeutic efficacy. In addition, patients should be monitored for the early and late
complications of PE, as well as for the complications of anticoagulation and other definitive
therapies. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section
on 'Monitoring and follow-up' and "Treatment, prognosis, and follow-up of acute pulmonary embolism
in adults", section on 'Management of recurrence on therapy' and 'Monitoring and followup' above.)

ACKNOWLEDGMENT

We are saddened by the death of Charles Hales, MD, who passed away in October 2015. UpToDate
wishes to acknowledge Dr. Hales' past work as an author for this topic.

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Topic 8253 Version 39.0

GRAPHICS
CT and FDG PET of a pulmonary infarct from embolism

Chest CT without contrast (A) and FDG PET images (B) show a cavitating nodule (arrow) and subsegmental air space opacity (arrowhead) in the
right lower lobe. Both are mildly FDG-avid with an indeterminate SUV of 2.1. Pathology of the nodule showed subacute infarction resulting
from pulmonary embolism. The subsegmental air space opacity could represent another infarct or inflammation.

CT: computed tomography; FDG: fluorodeoxyglucose (18F); PET: positron emission tomography; SUV: standardized uptake value.

Graphic 99736 Version 2.0

Lower extremity (CEAP) vein list

Superficial veins Deep veins Perforator veins

Telangiectasias or reticular veins Inferior vena cava Thigh
Great saphenous vein above the knee Common iliac vein Calf
Great saphenous vein below the knee Internal iliac vein
Small saphenous vein External iliac vein
Nonsaphenous veins Pelvic: gonadal, broad ligament veins, other
Common femoral vein
Deep femoral vein
Femoral vein*
Popliteal vein
Crural: anterior tibial, posterior tibial, peroneal veins (all paired)
Muscular: gastrocnemial, soleal veins, other

CEAP: Clinical-Etiology-Anatomy-Pathophysiology classification of lower extremity chronic venous disorders.

* Formerly referred to as the superficial femoral vein, a misnomer since it is a deep vein.

Graphic 77469 Version 4.0

Wells criteria and modified Wells criteria: Clinical assessment for pulmonary embolism

Clinical symptoms of DVT (leg swelling, pain with palpation) 3.0

Other diagnosis less likely than pulmonary embolism 3.0

Heart rate >100 1.5

Immobilization (≥3 days) or surgery in the previous four weeks 1.5

Previous DVT/PE 1.5

Hemoptysis 1.0

Malignancy 1.0

Probability Score
Traditional clinical probability assessment (Wells criteria)

High >6.0

Moderate 2.0 to 6.0

Low <2.0

Simplified clinical probability assessment (Modified Wells criteria)

PE likely >4.0

PE unlikely ≤4.0

DVT: deep vein thrombosis; PE: pulmonary embolism.

Data from van Belle A, Buller HR, Huisman MV, et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical
probability, D-dimer testing, and computed tomography. JAMA 2006; 295:172.

Graphic 54767 Version 4.0

Evaluation of the nonpregnant adult with low probability of pulmonary
embolism

CT pulmonary angiography is also called chest CT angiogram with contrast and is tailored
for to evaluate the pulmonary arteries. A conventional chest CT with contrast is not
adequate to exclude PE.

PE: pulmonary embolism; DVT: deep vein thrombosis; CT: computed tomography; PERC:
pulmonary embolism rule-out criteria.
* We prefer the Wells criteria to determine the pretest probability of PE, although the modified
Geneva score or clinical gestalt is also appropriate. Refer to UpToDate text for details.
¶ PERC is best used in the emergency department in patients with a low clinical pretest probability
of PE and is not suitable for other clinical settings or in those with an intermediate or high pretest
probability of PE. Some experts choose not to use PERC and proceed directly to sensitive D-Dimer
testing.
Δ Feasibility requires adequate scanner technology. Also the patient must be able to lie flat, to
cooperate with exam breath-holding instructions, have a body habitus that can fit into scanner, and
no contraindications for iodinated contrast.
◊ Repeat CT pulmonary angiography for more definitive results may be worthwhile if the factor
causing poor image quality can be mitigated (eg, patient more capable of cooperating with
positioning and breath-holding instructions). Repeat imaging is unlikely to prove useful if exam
was nondiagnostic due to factors such as scanner technology, body habitus, or indwelling metallic
foreign bodies.
§ Feasibility requires a chest radiograph demonstrating clear lungs and a patient able to lie still for
>30 minutes.
¥ Further testing first involves revisiting the feasibility of CT pulmonary angiography. If CT
pulmonary angiography is still not feasible then lower extremity compression ultrasonography with
Doppler is appropriate.

Graphic 113963 Version 1.0

Evaluation of the nonpregnant adult with intermediate probability of
pulmonary embolism

CT pulmonary angiography is also called chest CT angiogram with contrast and is tailored
for to evaluate the pulmonary arteries. A conventional chest CT with contrast is not
adequate to exclude PE.

PE: pulmonary embolism; CT: computed tomography.

* We prefer the Wells criteria to determine the pretest probability of PE, although the modified
Geneva score or clinical gestalt is also appropriate. Refer to UpToDate text for details.
¶ Some experts proceed directly to CT pulmonary angiography in patients on the higher end of the
intermediate risk spectrum (eg, Wells score 4 to 6) or in those with limited cardiopulmonary
reserve.
Δ Feasibility requires adequate scanner technology. Also the patient must be able to lie flat, to
cooperate with exam breath-holding instructions, have a body habitus that can fit into scanner, and
no contraindications for iodinated contrast.
◊ Repeat CT pulmonary angiography for more definitive results may be worthwhile if the factor
causing poor image quality can be mitigated (eg, patient more capable of cooperating with
positioning and breath-holding instructions). Repeat imaging is unlikely to prove useful if exam
was nondiagnostic due to factors such as scanner technology, body habitus, or indwelling metallic
foreign bodies.
§ Feasibility requires a chest radiograph demonstrating clear lungs and a patient able to lie still for
>30 minutes.
¥ Further testing first involves revisiting the feasibility of CT pulmonary angiography. If CT
pulmonary angiography is still not feasible then lower extremity compression ultrasonography with
Doppler is appropriate.

Graphic 113962 Version 1.0

Evaluation of the nonpregnant adult with high probability of pulmonary
embolism

CT pulmonary angiography is also called chest CT angiogram with contrast and is tailored for
to evaluate the pulmonary arteries. A conventional chest CT with contrast is not adequate to
exclude PE.

PE: pulmonary embolism; CT: computed tomography.

* We prefer the Wells criteria to determine the pretest probability of PE, although the modified
Geneva score or clinical gestalt is also appropriate. Refer to UpToDate text for details.
¶ Feasibility requires adequate scanner technology. Also the patient must be able to lie flat, to
cooperate with exam breath-holding instructions, have a body habitus that can fit into scanner, and
no contraindications for iodinated contrast.
Δ Repeat CT pulmonary angiography for more definitive results may be worthwhile if the factor
causing poor image quality can be mitigated (eg, patient more capable of co-operating with
positioning and breath-holding instructions). Repeat imaging is unlikely to prove useful if exam is
nondiagnostic from factors such as scanner technology, body habitus, or indwelling metallic foreign
bodies.
◊ Feasibility requires a chest radiograph demonstrating clear lungs and a patient able to lie still for
>30 minutes.
§ Further testing first involves revisiting the feasibility of CT pulmonary angiography. If CT
pulmonary angiography is still not feasible then lower extremity compression ultrasonography with
Doppler is appropriate.

Graphic 113961 Version 1.0

Pulmonary embolism severity index scores: Full and simplified

Pulmonary embolism severity index (PESI) - Full

Clinical feature Points

Age x (eg, 65)

Male gender 10

History of cancer 30

Heart failure 10

Chronic lung disease 10

Pulse ≥110/min 20

Systolic blood pressure <100 mmHg 30

Respiratory rate ≥30/min 20

Temperature <36° Celcius 20

Altered mental status 60

Arterial oxygen saturation <90 percent 20

Class I Low risk <66

Class II 66 to 85

Class III High risk 86 to 105

Class IV 106 to 125

Class V >125

Simplified pulmonary embolism severity index (sPESI)

Clinical feature Points

Age >80 years 1

History of cancer 1

Chronic cardiopulmonary disease 1

Pulse ≥110/min 1

Systolic blood pressure <100 mmHg 1

Arterial oxygen saturation <90 percent 1

Low risk 0

High risk ≥1

The full PESI score is rarely calculated in clinical practice since it is generally considered cumbersome. In contrast, sPESI is brief, contains a
limited number of easily accessible parameters, and is therefore, much more practical.

Adapted from:
1. Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005;
172:1041.
2. Jiménez D, Aujesky D, Moores L, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute
symptomatic pulmonary embolism. Arch Intern Med 2010; 170:1383.

Graphic 90549 Version 4.0

Contributor Disclosures
B Taylor Thompson, MD Nothing to disclose Christopher Kabrhel, MD, MPH Grant/Research Support: Siemens
[Venous thromboembolism (D-dimer test)]; Janssen [Venous thromboembolism (Rivaroxaban)]; Diagnostica Stago
[Venous thromboembolism (D-dimer test)]. Consultant/Advisory Board: Siemens [Venous thromboembolism (D-dimer
test)]; Janssen [Venous thromboembolism (Rivaroxaban)]. Jess Mandel, MD Nothing to disclose Geraldine Finlay,
MD Consultant/Advisory Boards: LAM Board of directors, LAM scientific grant review committee for The LAM
Foundation.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed
by vetting through a multi-level review process, and through requirements for references to be provided to support the
content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of
evidence.

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