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Official reprint from UpToDate®

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Clinical presentation, evaluation, and diagnosis of the

nonpregnant adult with suspected acute pulmonary
embolism
AUTHORS: B Taylor Thompson, MD, Christopher Kabrhel, MD, MPH, Constantino Pena, MD
SECTION EDITORS: Jess Mandel, MD, MACP, ATSF, FRCP, Korilyn S Zachrison, MD, MSc
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: Jan 2024.

This topic last updated: Jan 19, 2024.

INTRODUCTION

Acute pulmonary embolism (PE) is a common and sometimes fatal disease. The approach to the
evaluation should be efficient while simultaneously avoiding the risks of unnecessary testing so
that therapy can be promptly initiated and potential morbidity and mortality avoided [1].

The clinical manifestations, evaluation, and diagnosis of PE are discussed in this topic. The
pathophysiology, treatment, and prognosis of PE as well as the diagnosis of PE during
pregnancy are reviewed separately. (See "Epidemiology and pathogenesis of acute pulmonary
embolism in adults" and "Treatment, prognosis, and follow-up of acute pulmonary embolism in
adults" and "Pulmonary embolism in pregnancy: Clinical presentation and diagnosis".) (Related
Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically
stable and Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically
unstable despite resuscitative efforts.)

Approaches to diagnosis outlined in this topic are, in general, consistent with strategies
outlined by several international societies including The American College of Physicians, The
European Society of Cardiology, The European Respiratory Society, American College of
Emergency Physicians, American College of Radiology, and others [1-5].

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CLINICAL PRESENTATION

PE has a wide variety of presenting features, ranging from no symptoms to shock or sudden
death [6-9]. The most common presenting symptom is dyspnea followed by chest pain
(classically pleuritic but often dull) and cough. However, many patients, including those with
large PE, have mild or nonspecific symptoms or are asymptomatic. For example, a meta-
analysis of 19 studies (25,343 patients) found that clinical impression alone had a sensitivity and
specificity of 85 and 51 percent, respectively, for the diagnosis of PE [10].Thus, it is critical that a
high level of suspicion be maintained such that clinically relevant cases are not missed.

History and examination — The most common symptoms in patients with PE were identified
in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) group ( table 1)
[7]. They include the following:

● Dyspnea at rest or with exertion (73 percent)

● Pleuritic pain (66 percent)
● Cough (37 percent)
● Orthopnea (28 percent)
● Calf or thigh pain and/or swelling (44 percent)
● Wheezing (21 percent)
● Hemoptysis (13 percent)

Less common presentations include transient or persistent arrhythmias (eg, atrial fibrillation),
presyncope, syncope, and hemodynamic collapse (<10 percent each) [11,12]. Hoarseness from a
dilated pulmonary artery is a rare presentation (Ortner syndrome) [13].

The onset of dyspnea is frequently (but not always) rapid, usually within seconds (46 percent) or
minutes (26 percent) [9]. Dyspnea may be less frequent in older patients with no previous
cardiopulmonary disease. Dyspnea is more likely to be present in patients who present with PE
in the main or lobar vessels.

Approximately 10 percent of patients present with the symptoms of an infarcted lung, usually
due to smaller, more peripheral emboli. Pleuritic pain is typical in this population due to
inflammation of the pleura. Hemorrhage from the infarcted lung is also thought to be
responsible for hemoptysis. (See "Epidemiology and pathogenesis of acute pulmonary
embolism in adults", section on 'Pathogenesis and pathophysiology'.)

Retrospective studies report syncope as the presenting symptom in 10 percent or less of cases.
Conversely, among those presenting with syncope, rates of PE ranging from 1 to 17 percent

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have been reported [14-22]. Rates may be higher in those hospitalized with syncope [19,22].
Highlighting syncope as a manifestation of PE, 560 patients seen in an emergency department
(ED) with a first episode of syncope who were admitted to hospital underwent a rigorous
investigation for PE that involved D-dimer and computed tomography (CT) pulmonary
arteriography (CTPA) [19]. In this population, the prevalence of PE was 17 percent, higher in
those who had no other identifiable etiology for syncope (25 percent). Although those
discharged from the ED did not undergo formal evaluation for PE, when they were included in
the analysis, the rate of PE was lower and closer to that seen in other retrospective studies (4
percent). Syncope may indicate a high burden of thrombus since up to two-thirds of patients
with PE who present with syncope have large thrombi located in the mainstem or lobar arteries
[11,12]. The reasons for syncope in patients with PE are poorly understood but may be partially
explained by transient arrhythmias as thrombus travels through the heart or transient
obstruction as the embolus transits the pulmonic valve.

Some patients have a delayed presentation over weeks or days. One prospective study reported
that patients with a delayed presentation beyond one week tended to have larger, more
centrally located PE compared with patients who presented within seven days (41 versus 26
percent) [23]. Symptoms and signs of PE may also evolve over time such that patients who
initially present with mild symptoms may become increasingly symptomatic or
hemodynamically unstable, sometimes very quickly (minutes to hours). This may be secondary
to recurrent embolization or progressive pulmonary hypertension secondary to
vasoconstriction. Similarly, as a pulmonary infarct evolves, patients may develop progressive
dyspnea, hypoxemia, pleuritic pain, and hemoptysis. (See "Epidemiology and pathogenesis of
acute pulmonary embolism in adults", section on 'Pathogenesis and pathophysiology'.)

Importantly, symptoms may be mild or absent, even in large PE [6,9,24]. Although the true
incidence of asymptomatic PE is unknown, one systematic review of 28 studies found that,
among the 5233 patients who had a deep vein thrombosis (DVT), one-third also had
asymptomatic PE [24].

Common presenting signs on examination include [9]:

● Tachypnea (54 percent)

● Calf or thigh swelling, erythema, edema, tenderness, palpable cords (47 percent)
● Tachycardia (24 percent)
● Rales (18 percent)
● Decreased breath sounds (17 percent)
● An accentuated pulmonic component of the second heart sound (15 percent)
● Jugular venous distension (14 percent)
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● Fever, mimicking pneumonia (3 percent)

Although upper extremity DVT (UEDVT) embolizes less commonly than lower extremity DVT,
symptoms of UEDVT (eg, arm pain or tightness) should also raise the suspicion of PE. (See
"Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein
thrombosis of the lower extremity" and "Overview of thoracic central venous obstruction".)

PE is a common cause of sudden cardiac arrest or circulatory collapse (8 percent), especially

among patients younger than 65 years old [9,25,26]. Among such patients, either dyspnea or
tachypnea is present in 91 percent. Massive PE may be accompanied by acute right ventricular
failure manifested by increased jugular venous pressure, a right-sided third heart sound, a
parasternal lift, cyanosis, and obstructive shock. However, shock may also develop in patients
with smaller PE who have severe underlying pulmonary hypertension. A transition from
tachycardia to bradycardia, or from a narrow complex to a broad complex tachycardia (ie, right
bundle branch block), is an ominous sign of right ventricular strain and impending shock. PE
should be suspected anytime there is hypotension accompanied by an elevated central venous
pressure that is not otherwise explained by acute myocardial infarction, tension pneumothorax,
pericardial tamponade, or a new arrhythmia [27,28]. (See "Definition, classification, etiology,
and pathophysiology of shock in adults".)

Laboratory tests — Laboratory tests are not diagnostic but alter the clinical suspicion for PE,
confirm the presence of alternative diagnoses, and provide prognostic information in the event
that PE is diagnosed:

● Complete blood count and serum chemistries – Routine laboratory findings include
leukocytosis, increased erythrocyte sedimentation rate (ESR), elevated serum lactate,
elevated serum lactate dehydrogenase (LDH), and aspartate aminotransferase (AST).
Serum creatinine and the estimated glomerular filtration rate (eGFR) helps determine the
safety of administering contrast for angiography.

● Arterial blood gas (ABG) and pulse oximetry – Unexplained hypoxemia in the setting of
a normal chest radiograph should raise the clinical suspicion for PE and prompt further
evaluation. ABGs are often abnormal among patients suspected of having PE; however,
they can be normal in up to 18 percent of patients with PE [29]. Abnormal gas exchange
may be due to, and/or worsened by, underlying cardiopulmonary disease [30]. Common
abnormalities seen on ABGs include one or more of the following [7,29,31] (see "Arterial
blood gases"):

• Hypoxemia (74 percent)

Widened alveolar-arterial gradient for oxygen (62 to 86 percent)
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• Respiratory alkalosis and hypocapnia (41 percent)

Hypercapnia, respiratory, and/or lactic acidosis are uncommon but can be seen in patients
with massive PE associated with obstructive shock and respiratory arrest.

Abnormal oxygenation may be of prognostic value. As an example, patients with

hypoxemia or room air pulse oximetry readings <95 percent at the time of diagnosis are at
increased risk of complications, including respiratory failure, obstructive shock, and death
[32]. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults",
section on 'Outpatient anticoagulation'.)

● Brain natriuretic peptide (BNP) – Elevated BNP has limited diagnostic value in patients
suspected of having PE [33,34]. However, elevated BNP or its precursor, N-terminal (NT)-
proBNP may be useful prognostically for risk stratification of patients diagnosed with
acute PE. (See "Epidemiology and pathogenesis of acute pulmonary embolism in adults",
section on 'Prognosis'.)

● Troponin – Similarly, serum troponin I and T levels are useful prognostically but not
diagnostically [35-39]. As markers of right ventricular dysfunction, troponin levels are
elevated in 30 to 50 percent of patients who have a moderate to large PE [35,40] and are
associated with clinical deterioration and death after PE. Troponin elevations usually
resolve within 40 hours following PE, in contrast to the more prolonged elevation after
acute myocardial injury [41]. (See "Epidemiology and pathogenesis of acute pulmonary
embolism in adults", section on 'Prognosis'.)

● D-dimer – The role of D-dimer in the diagnostic evaluation of suspected PE is discussed

below. (See 'D-dimer' below.)

Electrocardiography — Electrocardiogram (ECG) abnormalities, although common in patients

with suspected PE, are nonspecific [42-46]. The most common findings are tachycardia and
nonspecific ST-segment and T-wave changes (70 percent) [8].

Abnormalities historically considered to be suggestive of PE (S1Q3T3 pattern, right ventricular

strain, new incomplete right bundle branch block) are uncommon (less than 10 percent) [47,48].
ECG abnormalities that are associated with a poor prognosis in patients diagnosed with PE
include [42,43,45]:

● Atrial arrhythmias (eg, atrial fibrillation)

● Bradycardia (<50 beats per minute) or tachycardia (>100 beats per minute)
● New right bundle branch block

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● Inferior Q-waves (leads II, III, and aVF)

● Anterior ST-segment changes and T-wave inversion
● S1Q3T3 pattern

Chest radiograph — Nonspecific abnormalities on chest radiography are common (eg,

atelectasis, effusion) in PE, but a normal chest radiograph can be seen in 12 to 22 percent of
patients [7,8,49]. A chest radiograph is typically performed in most patients suspected of PE to
look for an alternative cause of the patient's symptoms. It is also performed to determine
eligibility for ventilation perfusion (V/Q) scanning (see 'Ventilation perfusion scan' below).
However, it is not necessary if a CTPA is planned.

A Hampton hump, Westermark sign, and Palla sign are rare but, when present, should raise the
suspicion for PE [50]. Hampton hump is a shallow, hump-shaped opacity in the periphery of the
lung, with its base against the pleural surface and hump towards the hilum ( image 1).
Westermark sign is the demonstration of a sharp cut-off of pulmonary vessels with distal
hypoperfusion in a segmental distribution within the lung ( image 2). Palla sign is an enlarged
descending pulmonary artery that has a 'sausage' appearance [51].

HEMODYNAMICALLY UNSTABLE PATIENTS

PE is stratified into massive, submassive, and low-risk based upon the presence or absence of
hypotension and right ventricular dysfunction or dilation. This stratification is associated with
mortality risk [52,53]. In the small percentage of patients with hemodynamic instability, either
at presentation or during the course of their illness, the symptoms range from mild
hypotension to overt obstructive shock. The initial approach should focus upon restoring
perfusion with intravenous fluid resuscitation and vasopressor support (if needed), as well as
oxygen supplementation and airway stabilization with intubation and mechanical ventilation (if
needed).

In this population, diagnosis and therapy are often approached simultaneously. However, in this
section, we focus on diagnosis; the definition of hemodynamic instability and the approach to
therapy are discussed separately. (See "Treatment, prognosis, and follow-up of acute
pulmonary embolism in adults", section on 'Initial approach and resuscitation' and "Treatment,
prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Hemodynamically
unstable patients'.)

Hemodynamic stability restored following resuscitation — For patients in whom

hemodynamic stability is restored following brief resuscitation (eg, for 15 minutes), we suggest

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the following approach:

● High suspicion for PE – For patients in whom the suspicion for PE is high, we prefer
immediate anticoagulation (provided there is no contraindication) and definitive
diagnostic imaging, usually CT pulmonary angiogram (CTPA). This approach is contingent
upon prompt access to imaging and the presence of staff that can administer
cardiopulmonary resuscitation (CPR) and/or empiric thrombolytic therapy in the event that
the patient decompensates during testing.

● Low or moderate suspicion for PE – For patients with a low or moderate suspicion of PE,
the same approach to diagnosis and empiric anticoagulation should be used as for
patients who are hemodynamically stable. (See 'Hemodynamically stable patients' below.)

Hemodynamically unstable despite resuscitation — For patients who remain

hemodynamically unstable (eg, systolic pressure <90 mmHg for 15 minutes or longer or clear
evidence of shock) despite adequate resuscitation, definitive testing is typically considered
unsafe. In these circumstances, bedside lower extremity ultrasonography and transthoracic
echocardiography may be used to obtain a presumptive diagnosis of PE. In this population of
unstable patients, a presumptive diagnosis of PE may justify the administration of potentially
life-saving therapies (eg, thrombolysis). (See "Treatment, prognosis, and follow-up of acute
pulmonary embolism in adults", section on 'Hemodynamically unstable patients'.) (Related
Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically
unstable despite resuscitative efforts.)

● While bedside lower extremity compression ultrasonography does not diagnose PE, it is
sufficient for the diagnosis of deep venous thrombosis (DVT), which is sufficient to initiate
treatment. (See "Evaluation of and initial approach to the adult patient with
undifferentiated hypotension and shock" and 'Lower-extremity ultrasound with Doppler'
below.)

● Similarly, the presence of new right ventricular strain or direct visualization of thrombus
within the heart (ie, clot-in-transit) does not make a definitive diagnosis of PE but
treatment should be initiated based upon these findings in an unstable patient (provided
there is no contraindication). Although visualization of thrombus in a proximal pulmonary
artery is diagnostic of PE, it is rare and generally only seen on transesophageal
echocardiography. Early systolic notching of the pulsed wave Doppler waveform in the
right ventricular outflow tract may be present in submassive or massive pulmonary
embolism but further study is warranted before this sign can be routinely interpreted as
conclusive evidence of PE [54]. (See 'Echocardiography' below.)

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In many academic centers, the initial evaluation and resuscitation of hemodynamically unstable
patients suspected as having PE are often performed in conjunction with pulmonary embolism
response teams (PERTs). These teams are comprised of cardiothoracic surgeons, pulmonary and
intensive care unit clinicians, cardiologists, emergency clinicians, and interventional radiologists
[55-57]. In centers with limited resources (eg, without PERT or without bedside
ultrasonography), the responding clinician must rely upon clinical judgment to assess the risk-
benefit ratio of empiric anticoagulation and/or thrombolysis in the absence of definitive testing.
(See 'Determining the pretest probability of pulmonary embolism' below.)

Treatment of hemodynamically unstable PE and the role of bedside ultrasonography in the

evaluation of shock are discussed separately. (See "Evaluation of and initial approach to the
adult patient with undifferentiated hypotension and shock" and "Treatment, prognosis, and
follow-up of acute pulmonary embolism in adults", section on 'Hemodynamically unstable
patients'.)

HEMODYNAMICALLY STABLE PATIENTS

The majority of patients with PE are hemodynamically stable on presentation [9]. In this
population of patients, sufficient time is available to adopt a systematic approach for the
diagnosis of PE.

Overview — Several approaches for hemodynamically stable nonpregnant adult patients with
suspected PE have been proposed [1-3,58-64]. Their purpose is to efficiently diagnose all
clinically important PE while simultaneously avoiding the risks of unnecessary testing. We prefer
an approach that selectively integrates clinical evaluation, three-tiered pretest probability (PTP)
assessment, PE rule out criteria (PERC), D-dimer testing, and imaging ( algorithm 1 and
algorithm 2 and algorithm 3). CT pulmonary angiogram (CTPA) is the imaging modality of
choice. However, algorithms that use a ventilation perfusion (V/Q) scan are appropriate when
CTPA is contraindicated, not feasible, or inconclusive. (See 'Computed tomography pulmonary
angiography' below and 'Alternate imaging approaches' below.) (Related Pathway(s):
Pulmonary embolism: Diagnostic evaluation in adults who are hemodynamically stable.)

Empiric anticoagulation while waiting for test results should be individualized according to the
clinical suspicion for PE, the anticipated timing of definitive testing, and the risk of bleeding, the
details of which are discussed separately. (See "Treatment, prognosis, and follow-up of acute
pulmonary embolism in adults", section on 'Empiric anticoagulation' and "Venous
thromboembolism: Initiation of anticoagulation".)

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Despite the publication of several well-validated protocols and clinical decision rules targeted at
avoiding the overuse of CTPA, real-world data suggest increased use of CTPA [65-67]. One five-
year retrospective international analysis of almost 9000 CTPA studies performed for suspected
PE in the emergency department (ED) reported an increase in CTPA use over the five-year
period of the study (836 versus 1112 per 100,000 ED visits) [65]. More patients were diagnosed
with low-risk PE (eg, simplified PE severity index score; 13 percent increase), and higher rates of
ambulatory management were noted. More research is needed to determine the reasons for
increased use of CTPA and the potential clinical implications.

Determining the pretest probability of pulmonary embolism — Whenever PE is suspected,

the PTP for PE should be estimated by clinical gestalt assessment or calculated using a validated
PTP score (eg, Wells score, Modified Wells score, or Modified Geneva score) [10,58,59,68-73].
Although gestalt estimates and calculating probability scores have comparable sensitivity when
combined with D-dimer testing, meta-analyses suggest that probability scores may have higher
specificity [10,73] and increase the diagnostic yield of CTPA [74].

Although use of Wells, Modified Wells ( table 2) (calculator 1), or Modified Geneva score
( table 3) (calculator 2) is acceptable, based upon extensive validation and our clinical
experience, we prefer that the Wells criteria be applied and the score calculated to determine
probability of PE into a three-tiered system of:

● Low (score <2) (see 'Low probability of pulmonary embolism' below)

● Intermediate (score 2 to 6) (See 'Intermediate probability of pulmonary embolism' below.)
● High (score >6) (see 'High probability of pulmonary embolism' below)

Subsequent testing is dependent upon the likelihood of PE, which is discussed in the sections
below. (See 'Computed tomography pulmonary angiography' below and 'Alternate imaging
approaches' below.)

Wells criteria include the following ( table 2) (calculator 1):

● Clinical symptoms of deep vein thrombosis (DVT) (3 points)

● Other diagnoses are less likely than PE (3 points)
● Heart rate >100 (1.5 points)
● Immobilization three or more days or surgery in previous four weeks (1.5 points)
● Previous DVT/PE (1.5 points)
● Hemoptysis (1 point)
● Malignancy (1 point)

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Despite validation of the Wells criteria, for unclear reasons, clinicians do not use them or use
them incorrectly in up to 80 percent of patients [75,76]. In addition, they may not be as accurate
in older or critically ill patients [71,77]. Wells criteria have best validated in outpatients
presenting with suspected PE. However, one study of hospitalized patients, reported a
sensitivity and specificity of 72 and 62 percent, respectively [78]; the addition of D-dimer to
Wells criteria improved the sensitivity to 99 and reduced the specificity to 11 percent.

The Wells criteria can also be used to classify patients into a two-tiered system: patients are
likely (score >4) or unlikely (score ≤4) to have PE. Although it has been validated and is equally
as useful, we prefer to use the three-tiered classification of low, intermediate, and high
probability since this classification allows D-dimer testing to be applied to both low- and
intermediate-risk patients (score ≤6), further reducing the need for unnecessary testing. It can
also be used to interpret results of V/Q scans more accurately.

A retrospective study compared the Wells score with the YEARS algorithm and found that the
YEARS algorithm was more sensitive (97 versus 74 percent) but less specific (14 versus 34
percent) for the diagnosis of PE [79]. The YEARS algorithm is described below. (See 'D-dimer'
below.)

Low probability of pulmonary embolism — For patients with a low probability of PE (eg, PTP
<15 percent, Wells score <2), we apply the PERC ( table 4) to determine whether or not
diagnostic evaluation with D-dimer is indicated ( algorithm 3). While some experts measure
D-dimer in all low-risk patients, our preference to use PERC is based upon validity of this
approach in this population, and the likely reduction (approximately 20 percent) of unnecessary
testing (ie, D-dimer and imaging) associated with its use [80]. When the PERC rule is chosen, the
following applies to patients for whom the clinician has determined that a diagnostic evaluation
for PE is indicated (see 'PERC rule' below):

● For patients who fulfill all eight PERC criteria, no further testing is required
● For patients who do not fulfill all eight criteria, further testing with sensitive D-dimer
measurement is indicated

In low-risk patients where PERC cannot be applied (eg, inpatients, critically ill patients) or PERC
is positive, D-dimer testing is indicated and the following applies (see 'D-dimer' below):

● When the D-dimer level is <500 ng/mL (fibrinogen equivalent units), no further testing is
required
● When the D-dimer level is ≥500 ng/mL (fibrinogen equivalent units), diagnostic imaging
should be performed, preferably with CTPA (see 'Computed tomography pulmonary
angiography' below)
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PERC rule — The PE rule out criteria (PERC) rule was designed to identify patients with a low
clinical probability of PE in whom the risk of unnecessary testing outweighs the risk of PE [2,80-
83] (see 'Low probability of pulmonary embolism' above). The PERC rule has eight criteria
( table 4) (calculator 3):

• Age <50 years

• Heart rate <100 beats/minute
• Oxyhemoglobin saturation ≥95 percent
• No hemoptysis
• No estrogen use
• No prior DVT or PE
• No unilateral leg swelling
• No surgery/trauma requiring hospitalization within the prior four weeks

In patients with a low probability of PE who fulfill all eight criteria, the likelihood of PE is
sufficiently low that further testing is not indicated. Best illustrating the value of PERC is a
crossover cluster-randomized noninferiority trial of 1916 ED patients with a low gestalt clinical
probability of PE (ie, 15 percent probability of PE) that compared PERC with conventional
assessment (ie, an evaluation that included measuring a D-dimer level to determine further
testing) [84]. There was no difference in the rate of PE and only one patient in the PERC group
(0.1 percent) developed PE during the three- month follow-up period, compared with none in
the conventional group. The application of PERC resulted in a reduction in the proportion of
patients undergoing CTPA (13 versus 23 percent) and also reduced the ED stay by 36 minutes.
Another multicenter prospective cohort study of 8138 ED patients with a low clinical suspicion
for PE reported that among those who fulfilled all of the eight criteria, only 15 (less than 1
percent) were diagnosed with DVT or PE within the subsequent 45 days [80]. Another study
evaluated PERC in patients with a low probability of PE based upon the Wells criteria (score <2)
( table 2) (calculator 1), in lieu of a gestalt estimate, and found a similarly high negative
predictive value and sensitivity [85].

PERC is only valid in clinical settings (typically the ED) with a low prevalence of PE (<15 percent)
[81]. In clinical settings with a higher prevalence of PE (>15 percent), the PERC-based approach
has been shown to have a substantially poorer predictive value [81]. Thus, it should not be used
in patients with an intermediate or high suspicion for PE or for inpatients suspected as having
PE.

D-dimer — An elevated D-dimer alone is insufficient to make a diagnosis of PE, but a normal
D-dimer can be used to rule out PE in patients with a low or intermediate probability of PE.

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D-dimer testing is best used in conjunction with clinical probability assessment ( table 2)
(calculator 1):

● For patients in whom the risk of PE is thought to be low, a normal D-dimer (<500 ng/mL
[fibrinogen equivalent units]) effectively excludes PE, and typically no further testing is
required. This includes patients who have had a prior PE and those with a delayed
presentation and hospitalized patients [23,78,86]. In contrast, an elevated D-dimer (>500
ng/mL [fibrinogen equivalent units]) should prompt further testing with diagnostic
imaging. (See 'Low probability of pulmonary embolism' above.)

● For most patients in whom the risk of PE is thought to be intermediate, a normal D-dimer
(<500 ng/mL [fibrinogen equivalent units]) also effectively excludes PE, and typically no
further testing is required. However, some experts believe that a subset of patients in the
intermediate risk category (eg, those in the upper zone of the intermediate range [eg,
Wells score 4 to 6 or Modified Geneva sore 8 to 10] or patients with limited
cardiopulmonary reserve) should undergo imaging based upon the higher probability of
PE in these patients since the sensitivity of D-dimer is not as good.

● For patients in whom the risk of PE is thought to be high, a normal D-dimer is not as
helpful for excluding the diagnosis and does not need to be performed. While a negative
D-dimer result does reduce the likelihood of PE in this population, it does not reduce it
sufficiently to rule out the diagnosis, with some data suggesting a prevalence of PE of 5
percent or more in those with a high pretest probability and a negative D-dimer [87-91]
(see 'High probability of pulmonary embolism' below). These patients should undergo
diagnostic imaging, preferably with CTPA.

We prefer "sensitive D-dimer" testing that uses quantitative or semiquantitative newer

generation immunoturbidimetric, latex-agglutination-based, or rapid enzyme-linked
immunosorbent assays (ELISA). These assays are preferred because of their high sensitivity, and
the fact that accurate results are available quickly (10 to 30 minutes) so that prompt decisions
regarding imaging can be made. For these assays, a level ≥500 ng/mL (fibrinogen equivalent
units) is usually considered positive, and <500 ng/mL (fibrinogen equivalent units) is considered
negative [87,92].

In contrast, early generation D-dimer assays (eg, qualitative rapid ELISA, first-generation latex,
and erythrocyte agglutination) are less accurate. In a meta-analysis of 108 studies, when
compared with other assays for D-dimer testing, the preferred assays (eg, semiquantitative
rapid ELISAs) were associated with a higher sensitivity (96 versus 90 percent) and negative
predictive value (98 versus 95 percent) [87]. The sensitivity of D-dimer is lower in patients with

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subsegmental PE compared with patients who have large main, lobar, or segmental PE (53
versus 93 percent) [93].

While D-dimer assays are highly sensitive, their specificity is low, usually between 40 and 60
percent. D-dimer results are often falsely positive, and the proportion of false positive results
increases with certain clinical conditions and any acute or inflammatory process (eg, age >50
years, recent surgery or trauma, acute illness, pregnancy or postpartum state, rheumatologic
disease, renal dysfunction [estimated glomerular filtration rate <60 mL/min/1.73 m2]), and sickle
cell disease ( table 5) [27,94-98].

Adjusted D-dimer — Although high-sensitivity D-dimer testing is preferred, adjusted D-dimer

levels based on certain criteria have been proposed and may be considered as an alternative in
patients with a low probability or low intermediate probability for PE. They should not be used
in those with high-probability or intermediate-high-probability for PE.

● Age-adjusted D-dimer – D-dimer levels rise with age such that using the traditional cutoff
value of <500 ng/mL (fibrinogen equivalent units) results in reduced specificity of D-dimer
testing in older patients (>50 years), a population in whom PE is common. Several studies
report its use [2,63,99-104] with the most commonly used formula for age adjustment as:

Age (if over 50 years) x 10 = cutoff value in ng/mL (fibrinogen equivalent units)

One meta-analysis of six trials reported that in patients unlikely to have PE by the Wells
criteria (score ≤4 ( table 2) (calculator 1)), compared with a negative fixed level D-dimer, a
negative age-adjusted D-dimer was associated with a 5 percent increase in the proportion
of patients in whom imaging can be safely withheld [103]. A major trial that supported its
role is discussed below (ADJUST-PE). (See 'Computed tomography pulmonary angiography'
below.)

● D-dimer and YEARS – Alternate D-dimer cut-offs have also been used. In one prospective
multicenter study, 3465 patients with suspected PE from an outpatient setting underwent
D-dimer testing and an assessment of pretest probability using the YEARS criteria [105].
The YEARS criteria include three items from the Wells score: clinical signs of DVT,
hemoptysis, and PE as the most likely diagnosis, all scored as a yes or no. PE was excluded
in patients with zero YEARS items and a D-dimer level <1000 ng/mL, and patients with ≥1
YEARS item and a D-dimer <500 ng/mL. All other patients underwent CTPA. Using this
algorithm, 13 percent of patients were diagnosed with PE. Among those in whom PE was
excluded, 0.6 percent had symptomatic PE confirmed at three-month follow-up [105], a
rate that was similar to that reported in studies that utilize fixed D-dimer level testing <500
ng/mL [58]. It was estimated that this algorithm would result in a 14 percent reduction in
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the number of CT scans performed, compared with using the Wells rule and a fixed D-
dimer level <500 ng/mL. In this study, using age-adjusted D-dimer had no additional value
to this algorithm [106], although subsequent studies have found additive value in using a
combined approach. A similar multicenter prospective observational study of 1134
emergency department patients suspected as having PE and referred for imaging per the
treating physician's discretion, reported a potential 14 percent reduction in those imaged
using YEARS criteria and a negative D-dimer (<1000 ng/mL for YEARS negative patients
and <500 ng/mL for YEARS positive patients) [107].The sensitivity and specificity of this
strategy were 93 and 55 percent respectively. This algorithm has been externally validated
for the safety of ruling out PE but caution was advised in patients with no YEARS items and
a D-dimer level <1000 ng/mL but above the age-adjusted cutoff [108].

● D-dimer adjusted to clinical probability (PEGeD) – In a prospective study of 2017

outpatients with suspected PE, patients with a low clinical probability (calculated per the
Wells score (calculator 1)) plus a negative D-dimer <1000 ng/mL and patients with a
moderate clinical probability and a negative D-Dimer <500 ng/mL did not undergo CTPA
(or anticoagulation) [109]. All other patients underwent imaging. During a three-month
follow-up, no patients with a low or moderate clinical probability plus a negative D-dimer
(<1000 ng/mL and <500 ng/mL, respectively) developed symptomatic venous
thromboembolism (VTE). Using the PEGeD protocol, 34 percent of patients were imaged
compared with an estimated 52 percent, had the traditional parameters (low clinical
pretest probability plus a D-dimer <500 ng/mL) been used to rule out PE (ie, a 17 percent
reduction in patients imaged). These findings are consistent with protocols that utilize D-
dimer adjusted to YEARS criteria (see above bullet) [105,107]. However, these results
mostly apply to patients in the low-probability pretest group since only 40 patients in this
study had a moderate pretest probability. In addition, whether this protocol applies to
inpatients or populations with a high prevalence of PE is also unknown.

● PERC-positive patients plus YEARS and age-adjusted D-Dimer – One noninferiority trial
randomized PERC-positive patients with a low clinical probability of PE and patients with
an intermediate probability for PE to further triage using YEARS criteria plus age-adjusted
D-dimer (intervention group) or to age-adjusted D-dimer alone (control group) and
compared VTE outcomes at three months [110]. In patients with zero YEARS criteria plus a
D-dimer <1000 ng/mL and in patients with one or more YEARS criteria plus a D-dimer level
less than the age-adjusted threshold, PE was considered to be excluded and no imaging
was performed. Imaging was performed if patients did not meet these criteria. Over 1200
patients were analyzed and the PE rate was 7.3 percent. The YEARS plus D-dimer strategy
resulted in a 10 percent reduction in patients who underwent chest imaging and a 1.6-

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hour reduction in the emergency department (ED) stay. There was also a nonsignificant
reduction in the rate of VTE at three months (one versus five patients; 0.15 percent versus
0.8 percent; adjusted difference, -0.64 percent, 97.5% CI -∞ to 0.21 percent). While
encouraging, the complexity of this protocol may not be practical in busy setting such as
the ED and could theoretically introduce error. In addition, it underestimates the value of
CT in identifying other etiologies for a patient's presenting symptoms.

● Comparing protocols – One meta-analysis compared diagnostic strategies for ruling out
PE including those that use clinical prediction rules, standard D-Dimer cutoffs (ie, 500
ng/mL), and adjusted D-Dimer (eg, age-adjusted or adjusted according to clinical pretest
probability [eg, YEARS]) [111]. Protocols that used pretest probability models and adjusted
D-Dimer were more efficient, as defined by the proportion of individuals considered to
have PE excluded (ie, more cases of PE are excluded without imaging). However, they also
had the highest failure rate as defined by the three-month rate of VTE after exclusion of PE
without imaging (ie, more cases of VTE are missed). In addition, protocols did not perform
uniformly across all subgroups, with the lowest efficiency observed in those who were 80
years of age or older and in patients with cancer.

Data discussing age-adjusted D-dimer and its role in patients with suspected DVT are provided
separately. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected
deep vein thrombosis of the lower extremity", section on 'D-dimer'.)

Intermediate probability of pulmonary embolism — For most patients in whom the

suspicion for PE is intermediate, a sensitive D-dimer level should be measured ( algorithm 2).
(See 'D-dimer' above.)

● When the D-dimer level is <500 ng/mL (fibrinogen equivalent units), no further testing is
typically required. However, some experts will proceed with diagnostic imaging in select
patients. For example, imaging may be considered in patients who have limited
cardiopulmonary reserve (ie, patients in whom PE would not be well tolerated) or those in
whom the clinical probability of PE was in the upper zone of the intermediate range (eg, a
Wells score of 4 to 6 or a Geneva score of 8 to 10).

● When the D-dimer level is ≥500 ng/mL (fibrinogen equivalent units), diagnostic imaging
should be performed, preferably with CTPA. (See 'Computed tomography pulmonary
angiography' below.)

D-dimer — Data that support the value of measuring D-dimer levels in patients in whom the
clinical suspicion is intermediate are discussed above. (See 'D-dimer' above.)

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High probability of pulmonary embolism — For most patients in whom the probability of PE
is high or in whom the suspicion is low or moderate and the D-dimer level is elevated, CTPA
should be performed ( algorithm 1).

When imaging is indicated, CTPA is the imaging modality of choice. V/Q scan is reserved for
patients in whom the CTPA is contraindicated (eg, history of moderate or severe contrast
allergy, high risk of contrast nephropathy [estimated glomerular filtration rate <30 mL/min/1.73
m2], or inability to tolerate CT scanning due to class 2 or 3 obesity or difficulty lying flat). V/Q
may also be indicated when CTPA is inconclusive, or when additional testing is needed, such as
when the clinical suspicion of PE remains high despite negative imaging. Hypotension and
advanced heart failure may limit the circulation of IV contrast and increase the likelihood of an
indeterminate CTPA [112].

● CTPA – For patients in whom CTPA is performed, the following applies (see 'Computed
tomography pulmonary angiography' below):

• A positive CTPA showing a filling defect confirms the diagnosis of PE. Treatment of PE
including subsegmental PE is discussed separately. (See "Treatment, prognosis, and
follow-up of acute pulmonary embolism in adults".)

• A negative CTPA indicates that the likelihood of PE is low. Typically, no further testing is
required, unless inadequate imaging is suspected (eg, the contrast bolus is poorly
timed and pulmonary arteries are inadequately opacified) or for another reason clinical
suspicion for PE remains high after negative CTPA. (See 'Alternate imaging approaches'
below.)

• An inconclusive CTPA result may necessitate alternate imaging, such as V/Q scanning
or lower-extremity venous ultrasonography. (See 'Alternate imaging approaches'
below.)

● V/Q scan – For patients in whom a V/Q scan is performed, management is dependent
upon the interpretation of the scan in the context of the pretest clinical probability for PE.
Although the Wells criteria were developed after the Prospective Investigation of
Pulmonary Embolism Diagnosis (PIOPED) study [6], it is appropriate to use Wells to stratify
risk ( table 2 and table 6) for the purposes of interpretation (see 'Ventilation
perfusion scan' below):

• In patients with a normal V/Q scan and any clinical probability, no further testing is
necessary.

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• In patients with a low-probability V/Q scan and low clinical probability (eg, Wells score
<2 ( table 2) (calculator 1)), no further testing is necessary.

• In patients with a high-probability V/Q scan and high clinical probability (eg, Wells score
>6 ( table 2) (calculator 1)), immediate treatment is indicated. (See "Treatment,
prognosis, and follow-up of acute pulmonary embolism in adults".)
• All other combinations of V/Q scan results and clinical pretest probabilities are
indeterminate (inconclusive), and further testing is required. (See 'Other imaging'
below.)

Computed tomography pulmonary angiography — For most patients with suspected PE,
CTPA, also called chest CT angiogram with contrast, is the first-choice diagnostic imaging
modality because it is sensitive and specific for the diagnosis of PE, especially when
incorporated into diagnostic algorithms. Alternate diagnoses may also be discovered using this
modality [113]. The imaging technology is widely available and, in most settings, the exam can
be performed on an urgent or emergent basis. In some cases, if contraindications to CTPA are
present but can be readily resolved (eg, premedication for a contrast allergy) and alternate
imaging such as V/Q scanning is not feasible, CTPA may be performed after a short delay (eg, 8
to 12 hours) with consideration for empiric anticoagulation while waiting. (See 'Alternate
imaging approaches' below and "Prevention of contrast-induced acute kidney injury associated
with computed tomography" and "Patient evaluation prior to oral or iodinated intravenous
contrast for computed tomography", section on 'Prevention'.)

CTPA imaging protocol — CTPA examination acquires thin (≤2.5 mm) section volumetric
images of the chest after a bolus administration of intravenous contrast that is timed precisely
for maximal enhancement of the pulmonary arteries. A multidetector (≥16 detector rows) CT
scanner is required to achieve sufficient diagnostic performance. Primary axial and multiplanar
reformations (commonly in the coronal plane) of the pulmonary arteries are routinely reviewed.
For optimal image quality, the patient should be able to hold still and hold their breath for
about 30 seconds. A chest CT with contrast not performed as a CTPA but for other indications
may incidentally detect pulmonary emboli but is not an adequate exam for excluding suspected
PE [113].

A CTPA result may be indeterminate for a number of reasons. The most common include
patient motion, large body habitus, beam hardening artefacts from metallic foreign bodies, and
suboptimal enhancement of the pulmonary artery usually due to abnormal cardiac output
[112]. Repeat CTPA 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). However, the risk of renal impairment due to repeated doses of
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intravenous contrast should be considered when determining whether and when to repeat
CTPA. Repeat imaging is unlikely to prove useful if CTPA is nondiagnostic from factors such as
scanner technology, body habitus, or indwelling metallic foreign bodies.

CTPA may be relatively contraindicated in patients with a history of moderate to severe

iodinated contrast allergy or renal insufficiency (eGFR <30 mL/min per 1.73 m2). The risk of
these contraindications must be weighed against the clinical importance of performing the
CTPA examination and the availability of alternative imaging approaches (eg, V/Q scan). If
clinically feasible, CTPA should be delayed for premedication for history of allergy or
intravenous hydration for renal insufficiency. (See "Prevention of contrast-induced acute kidney
injury associated with computed tomography" and "Patient evaluation prior to oral or iodinated
intravenous contrast for computed tomography", section on 'Prevention'.)

The approximate effective radiation dose from CTPA is 10 mSv and varies depending upon
patient size, scanner type, and imaging protocol. In young (age <30 years) adults or pregnant
patients who are undergoing multiple chest CT exams, minimizing cumulative radiation dose
may be a consideration in opting for alternative imaging techniques including ventilation
perfusion scanning, venous ultrasound, magnetic resonance pulmonary angiogram (MRPA), if
the necessary technology and expertise are available. (See 'Magnetic resonance pulmonary
angiography' below.)

CT venogram (CTV) of the lower extremities and pelvis with contrast to evaluate for DVT is not
routinely performed concurrently with the CTPA. CTV, when added to CTPA, may marginally
improve diagnostic yield. However, the added effective radiation dose from CTV is
approximately 6 mSv, thereby significantly increasing the radiation dose over the entire patient
population [114,115].

Results interpretation — Support for our preference for CTPA-based algorithms is

derived from a prospective, multicenter cohort study (Christopher study) of 3306 patients with
clinically suspected PE [58]. Patients were from an inpatient or outpatient setting and
categorized according to the modified Wells score as PE "likely" (score >4) or PE "unlikely" (score
≤4) ( table 2) (calculator 1). Patients classified as PE unlikely underwent sensitive D-dimer
testing; PE was considered excluded when the D-dimer level was <500 ng/mL (fibrinogen
equivalent units). PE unlikely patients who had a D-dimer level ≥500 ng/mL (fibrinogen
equivalent units) and PE likely patients underwent CTPA. When the CTPA confirmed PE, patients
were anticoagulated; when it excluded PE or was inconclusive (rarely), patients were not
treated. At three months follow-up, the rates of venous thromboembolism during follow-up
were low, as evidenced by the following:

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● Among 1028 untreated patients in whom PE was excluded by clinical assessment plus D-
dimer testing, there was one DVT (0.1 percent), four nonfatal PE (0.4 percent), and no fatal
PE.

● Among 1436 untreated patients in whom PE was excluded by CTPA, there were eight DVT
(0.6 percent), three nonfatal PE (0.2 percent), and seven fatal PE (0.5 percent).

● Among 674 treated patients in whom PE was detected by CTPA, there were six DVT (0.9
percent), three nonfatal PE (0.4 percent), and 11 fatal PE (1.6 percent).

A similarly designed prospective, multicenter study of 3346 patients with suspected PE in an

emergency department setting reported comparable results using age-adjusted D-dimer
cutoffs (ADJUST-PE) [63]. In ADJUST-PE, patients were classified as PE unlikely or likely. Those
who were PE unlikely underwent age-adjusted D-dimer testing (age [if over 50] multiplied by 10
[eg, normal D-dimer at 60 years is <600 ng/mL]). When the age-adjusted value was negative, no
further testing was performed. All other patients underwent CTPA. When CTPA was positive, PE
was confirmed and when CTPA was negative, PE was excluded. Patients with inconclusive CTPA
results or in whom CTPA could not be performed had additional imaging (eg, V/Q scan, serial
ultrasound [US], pulmonary angiogram) to diagnose or exclude PE. At three months follow-up,
rates of venous thromboembolism were low, as evidenced by the following:

● Among the 1141 untreated patients in whom PE was excluded by clinical assessment plus
age-adjusted D-dimer testing, there were only two cases (0.2 percent) of nonfatal PE.
Compared with using a fixed D-dimer level of <500 ng/mL, use of age-adjusted cutoffs
resulted in a 12 percent increase in the number of patients in whom a diagnosis of PE
could be safely excluded without further imaging.

● Among the 673 untreated patients ≥75 years in whom PE was excluded by clinical
assessment plus age-adjusted D-dimer testing, there were no thromboembolic events.

● Among the 1481 untreated patients in whom PE was excluded by CTPA, there was one DVT
(0.1 percent), four cases of nonfatal PE (0.2 percent), and two indeterminate events.

Age-adjusted D-dimer assessments are being increasingly used with significant institutional
variation.

Diagnostic performance — Most studies report that CTPA is >90 percent sensitive and
specific for the diagnosis of PE especially in the low and intermediate clinical risk groups. The
highest sensitivities (≥96 percent) are reported when CTPA is combined with a moderate to high
clinical probability assessment for PE, but lower when combined with a low clinical probability of

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PE [116-121]. The PIOPED II study reported that the sensitivity and specificity of multidetector
CTPA was 83 (90 percent when combined with high suspicion) and 96 percent, respectively,
using catheter-based pulmonary angiography as the reference standard [121]. However,
numerous cohort studies that use technically advanced scanners and specific CTPA protocols
have since consistently reported a low incidence (<2 percent) of PE in patients with low to
moderate clinical suspicion and a negative CTPA [122-126]. Nevertheless, there is a risk of PE in
those with a negative CTPA and a high clinical suspicion for PE (up to 5 percent when a ≤64
detector row multidetector CT [MDCT] is used), such that further testing (eg, lower-extremity
venous ultrasonography) may need to be considered [127].

CTPA is traditionally considered most accurate for the detection of large, main, lobar, and
segmental PE, and less accurate for the detection of smaller, peripheral subsegmental PE
(SSPE). Newer scanners with increased resolution have increased the detection of smaller
emboli [128-131]. As an example, one systematic review that included 2657 patients reported
improved detection of SSPE by multidetector row CTPA compared with single-detector row CTPA
(9.4 versus 4.7 percent) [128]. However, in some cases of isolated SSPE, repeat or additional
testing may need to be performed. Management of SSPE is discussed separately. (See
"Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on
'Patients with subsegmental PE'.)

One commonly cited benefit of CTPA is its ability to detect alternative pulmonary abnormalities
that may explain the patient's presenting symptoms and signs ( image 3) [132-135]. In one
observational study, 9 percent of CTPA examinations confirmed PE, while 33 percent identified
an alternative cause of the patient's symptoms [134]. In another retrospective review of 641
patients who underwent CTPA for suspected PE, an alternate diagnosis was discovered in 14
percent of patients who did not have PE, and 15 percent of these findings required immediate
attention [135].

Artificial intelligence (AI) has been proposed as a way to help radiologists interpret medical
images [136,137]. One retrospective study of 1202 patients with suspected PE examined the
role of an AI algorithm in the detection of PE [136]. Among 1202patients with suspected PE, 190
(15.8 percent) had true PE according to the study criterion standard that included both
radiologist and AI results. AI detected 219 patients with suspicion for PE, of which 176 (80
percent) were true PE and 43 (20 percent) were false positives. Of the true PE, 19 cases were
missed by radiologists. Sensitivity and negative predictive values were greater with AI, while
specificity and positive predictive values were greater with radiologists. Further data are needed
to determine what role AI could play in the diagnostic evaluation of patients with suspected PE.

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Alternate imaging approaches — When imaging is indicated and CTPA cannot be performed
or is inconclusive, we recommend V/Q scanning. In some cases, CTPA can be reconsidered if it
was previously contraindicated but subsequently becomes feasible (eg, when renal function
improves or after premedication for a contrast allergy). (See 'CTPA imaging protocol' above.)

Ventilation perfusion scan — V/Q scanning is mostly reserved for patients in whom CTPA
is contraindicated or inconclusive, or when additional testing is needed.

A normal chest radiograph is usually required prior to V/Q scanning. Scans performed on
patients with abnormal chest radiographs more likely to result in false positives as the images
rarely appear normal or low probability of PE in such patients. The patient is asked to lie still for
30 to 60 minutes for a V/Q scan. The approximate effective radiation dose is less than 2 mSv.

Support for our approach using V/Q scanning is based upon the following data:

● In PIOPED, V/Q scans were reported as one of the following [6]:

• Normal
• Low-probability PE
• Intermediate-probability PE
• High-probability PE

The risk of PE was reported in combination with pretest probability assessment ( table 6)
(see 'Determining the pretest probability of pulmonary embolism' above):

• Patients with a low clinical probability and a normal or low-probability V/Q scan had a
less than 4 percent chance of having a PE while those with an intermediate and high
probability scan had a 16 and 56 percent chance of having PE.

• Patients with a high clinical probability and a high-probability scan had a 96 percent
chance of having a PE. Those with normal scan had a 0 percent chance of having PE,
and those with a low- or intermediate-probability scan had a 40 and 66 percent chance
of having PE, respectively.

• Patients with an intermediate probability of PE and a high-probability scan had an 88

percent chance of having PE while all other combinations had probability of PE that
ranged from 6 to 28 percent.

Most patients have indeterminate scans, which is the major limitation of V/Q scanning
since an indeterminate scan is insufficient to either confirm or exclude the diagnosis of PE,
thereby necessitating additional testing.

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● One systematic review evaluated over 7000 patients from 25 prospective studies, 23 of
which included V/Q scan-based algorithms [138]. Three diagnostic strategies were
identified as safely excluding patients with PE over a three-month follow-up:

• Among patients with a low clinical probability of PE in whom PE was excluded by

normal D-dimer levels, PE occurred in less than 3 percent.

• Among patients in whom clinical probability combined with D-dimer assessment was
inconclusive, a normal perfusion scan (Q scan) safely excluded PE.

• Among patients with an intermediate-probability V/Q scan, holding therapy was safe
until further testing was performed (eg, catheter-based pulmonary angiography or
serial lower-extremity venous ultrasonography).

Although perfusion scanning alone is sometimes performed in limited cases, data to support its
use in the diagnosis of PE are limited.

Portable V/Q scans have been described for use in intensive care unit patients, although their
accuracy has not been compared with CTPA [139].

Other imaging — When neither CTPA nor V/Q scanning can be performed or are
inconclusive, we prefer noninvasive testing with lower extremity compression ultrasonography
with Doppler to evaluate for coexisting DVT. If the cumulative radiation dose in a young or
pregnant patient is a concern, and if the necessary technology and expertise is available, MRPA
could substitute for CTPA but is less sensitive and more dependent on the experience of the
technologist doing the scan. Catheter-based pulmonary angiography is more invasive and
slightly less sensitive than CTPA, and is usually reserved for patients where a concurrent
therapeutic intervention is planned. Occasionally, echocardiography can be used when a rapid
or presumptive diagnosis is needed in emergent circumstances but does not directly diagnose
PE.

Lower-extremity ultrasound with Doppler — A new diagnosis of DVT in the setting of

symptoms consistent with PE is highly suggestive, although not definitively diagnostic, of PE. As
such, Doppler ultrasonography can be used as an initial test in the evaluation of suspected PE,
as positive results can justify initiating anticoagulant treatment. However, because of the low
sensitivity of Doppler ultrasonography in this setting [140,141], it is not sufficient to rule out PE
and may be most useful for patients suspected of having a PE but in whom definitive imaging
(eg, CTPA, V/Q scanning) is contraindicated, indeterminate, or likely to be delayed.

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We suggest the following approach when Doppler ultrasonography is used in patients with
suspected PE in whom chest imaging is indeterminate or contraindicated:

● If lower-extremity Doppler ultrasonography is positive, patients can be treated (usually

anticoagulation).

● If Doppler ultrasonography is negative and the clinical suspicion for PE is low or

intermediate (calculator 1) ( table 2), it is generally considered safe to withhold
anticoagulation and monitor for DVT with serial ultrasonography until chest imaging can
be performed (eg, after treatment of contrast allergy) [138,142]. However, it is unknown
whether the same approach can be used in patients with poor cardiopulmonary reserve
(ie, patients that would not tolerate a PE); in these patients, empiric anticoagulation may
be appropriate. The optimal frequency of serial exams is unknown and at the discretion of
the clinician. (See "Overview of the treatment of proximal and distal lower extremity deep
vein thrombosis (DVT)", section on 'Low risk of embolization: Surveillance'.)

The safety of serial monitoring for DVT was illustrated in a prospective study of 874
patients with suspected PE, who had adequate cardiopulmonary reserve and a low or
intermediate-probability V/Q scan [142]. Six serial lower-extremity venous ultrasounds
were performed over a two-week period, and anticoagulation was administered only if the
ultrasonography was positive. At three months, fewer than 3 percent of patients
developed PE.

● If Doppler ultrasonography is negative and the suspicion for PE is high, further imaging
and/or or empiric anticoagulation should be attempted. The rationale for this approach is
that ultrasonography may be negative in the setting of PE, either because thrombus has
travelled to the lung or because clots in the calf and/or pelvic veins are not readily
detected by ultrasonography [143,144].

Whether proximal vein ultrasonography (which detects proximal vein DVT) or whole leg
ultrasonography (which detects proximal and calf vein DVT) should be performed is unknown.
Although some experts consider whole leg ultrasonography as ideal, the choice is often
institutionally determined.

Catheter-based pulmonary angiography — Pulmonary angiography, in which

contrast is injected under fluoroscopy via a catheter introduced into the right heart, was the
historical gold standard for the diagnosis of PE. With the widespread emergence of CTPA, this
procedure is infrequently used and reserved for rare circumstances for patients with a high
clinical probability of PE, in whom CTPA or V/Q scanning is nondiagnostic and in whom a
diagnosis determines an important clinical decision (eg, an intervention) ( image 4).
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Pulmonary angiography seems to be less accurate than CTPA and its diagnostic performance is
highly variable and dependent on the experience of the operator [138,145]. Consequently,
catheter-based pulmonary angiography is most often performed in patients in whom
concurrent therapy is planned since it can combine diagnosis with therapeutic interventions
aimed at clot lysis (eg, catheter-directed embolectomy and/or thrombolysis); its use in this
context is also dictated by local expertise. (See "Treatment, prognosis, and follow-up of acute
pulmonary embolism in adults", section on 'Embolectomy'.)

As the historical gold standard, the sensitivity and specificity of catheter-based pulmonary
angiography for the diagnosis of PE has not been formally evaluated. However, one
retrospective analysis of 20 cases from PIOPED II suggested that it may be less sensitive than
CTPA for the detection of small emboli [145,146]. Nonetheless, in patients with a negative
angiogram, the risk of subsequent symptomatic embolization is low (<2 percent) [6,138].

Although pulmonary angiography is generally well tolerated in the presence of hemodynamic

instability [147,148], the mortality of the procedure is approximately 2 percent but <1 percent
for those who are hemodynamically stable [147,148]. Morbidity occurs in approximately 5
percent of patients and is usually related to catheter insertion, contrast reactions, cardiac
arrhythmia, or respiratory insufficiency [27,147,149]. Radiation exposure depends upon the
length and complexity of the procedure, but is typically greater than that from CTPA [150,151].

Magnetic resonance pulmonary angiography — MRPA is not recommended as a

first-line test for the diagnosis of PE but may be an imaging option for diagnosis of PE in
patients in whom neither CTPA nor V/Q scan can be performed. Potential advantages of MRPA
are that no ionizing radiation is involved and the examination can be combined with MR
venography in the same sitting. (See "Clinical presentation and diagnosis of the nonpregnant
adult with suspected deep vein thrombosis of the lower extremity", section on 'Alternative
imaging'.)

The patient is asked to lie still in a magnetic resonance (MR) scanner for >30 minutes and
intravenous gadolinium is administered. (See "Patient evaluation before gadolinium contrast
administration for magnetic resonance imaging", section on 'Indications for giving contrast with
MRI'.)

Most importantly, in order to avoid a nondiagnostic result from inadequate image quality, MRPA
should only be performed at sites with the necessary technology and expertise. Technically
inadequate images can result from patient motion, scanner technology, and the timing the
gadolinium contrast bolus [152-156].

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MRPA was studied prospectively in 371 adults with suspected PE. Among the 75 percent of
patients who had technically adequate images, MRPA alone showed a sensitivity and specificity
of 78 percent and 99 percent, respectively [153]. Among the 48 percent of patients with
technically adequate images, MRPA and MR venography showed a sensitivity and specificity of
92 percent and 96 percent, respectively. Two additional prospective studies reported a similarly
poor sensitivity for MRPA alone [152,153,157]. Sensitivity was greater for emboli located in the
main/lobar and segmental vessels (100 and 84 percent, respectively), compared with
subsegmental vessels (40 percent; ie, emboli that should be easily detected on CTPA).

Echocardiography — Echocardiography can diagnose PE when thrombus is visualized

in the proximal pulmonary arteries, although this is a rare phenomenon. Although not
definitive, the diagnosis of PE is supported on echocardiography by the presence of clot in the
right heart or new right heart strain. The demonstration of any clot or new strain in
hemodynamically unstable patients with suspected PE may be useful if a rapid or presumptive
diagnosis is required to justify the emergency use of thrombolytic therapy [158-162]. However,
in most cases, particularly those who are hemodynamically stable, echocardiography is
generally considered insensitive (since abnormalities are frequently absent in patients with PE)
and nonspecific (since right ventricle [RV] abnormalities can be seen in other conditions
including chronic pulmonary disease, pulmonary hypertension, and right ventricular infarction);
in addition, the demonstration of new right heart strain may not be evident in the absence of a
prior echocardiogram. Although echocardiography has limited value diagnostically, it is most
useful for prognostic purposes in patients with confirmed PE (eg, new RV strain and RV
thrombus are poor prognostic indicators), the details of which are discussed separately. (See
"Echocardiographic assessment of the right heart" and "Epidemiology and pathogenesis of
acute pulmonary embolism in adults", section on 'Prognosis'.)

Approximately 30 to 40 percent of patients with PE have echocardiographic abnormalities

indicative of RV strain or pressure overload [163-165] and data suggest that there is direct
correlation between the extent of RV dysfunction and the degree of perfusion defects on lung
scans [160,161]. RV findings include:

● Increased RV size
● Decreased RV function
● Tricuspid regurgitation
● Abnormal septal wall motion
● McConnell sign
● Decreased tricuspid annular plane systolic excursion (TAPSE)

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Regional wall motion abnormalities that spare the right ventricular apex (McConnell sign) are
insensitive (77 percent) for the diagnosis of PE but, in those who demonstrate this sign, it may
be used to distinguish patients with RV strain from acute PE from those with pulmonary
hypertension, who tend to have global RV dysfunction [166]. In general, RV strain is insensitive
and nonspecific with one meta-analysis reporting a sensitivity of 53 percent and specificity of 61
percent [162].

Additional echocardiographic findings suggestive of PE that are uncommon but more

worrisome for PE include:

● RV thrombus – Among patients with intracardiac thrombus, one retrospective study

reported that 35 percent had PE [167], while another registry-based study reported that
among patients with known PE, approximately 4 percent have an RV thrombus [168].

● Pulmonary artery thrombus – Thrombus in the pulmonary arteries or main branches of

the pulmonary arteries may be seen on transesophageal echocardiography but is rare.

Investigational — Dual energy CT, single photon emission CT (SPECT), and multiorgan
ultrasound are being developed as imaging exams that could accurately and more safely
diagnose PE.

● Dual energy CT – Dual energy CT could reduce the amount of iodinated contrast needed
to perform CTPA examinations and increase the sensitivity for PE by imaging an iodine
map, which serves as a surrogate for lung perfusion [169]. Large cohort studies have not
been yet reported.

● SPECT – Technological advances in single photon emission CT ventilation and perfusion

imaging may allow for accurate diagnosis of PE without iodinated contrast administration
and it has a lower radiation dose than CTPA (unless SPECT-CT is performed). It may
increase detection of smaller pulmonary emboli. Preliminary studies suggest that SPECT is
as sensitive as CTPA and more sensitive than V/Q scanning [170-173]. The optimal
scanning technique is unknown (perfusion SPECT, V/Q SPECT, SPECT or V/Q SPECT with
non-enhanced CT) and its use may be limited to centers that have the technological
expertise to perform it.

● Multiorgan ultrasound – Multiorgan ultrasonography (ultrasound of the heart, lung, and

lower extremity) was prospectively examined in 357 patients suspected of having PE (Wells
score >4) [174]. A sensitivity and a specificity of 90 and 86 percent, respectively, was noted
when CTPA was used as a reference standard. Rare case reports describe the

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demonstration of thrombus in central pulmonary arteries on endobronchial

ultrasonography [175-177].

PATIENTS WITH SUSPECTED RECURRENT PULMONARY EMBOLISM

The approach to patients with suspected recurrent PE (days to years) should be the same as for
a first suspected event with some minor differences:

● In those who are hemodynamically stable, although the D-dimer level is less likely to be
negative in those with recurrence, it can still be useful in a limited proportion (<15 percent)
to distinguish those who should have imaging from those who should not. (See 'D-dimer'
above.)

● When feasible, prior imaging should be obtained in patients with suspected recurrence
(but should not delay treatment, when indicated). Many patients will present with similar
symptoms to their initial PE, not all of which are due to new thrombus, thus, it is useful to
distinguish symptoms that are due to new thrombus. However, the interpretation of
repeat imaging may be difficult since thrombus can migrate with time and the rates of clot
resolution are variable [178,179]. As examples:

• In a cohort of 79 patients with acute PE receiving anticoagulant therapy, complete clot

resolution occurred in 40 percent of patients within one week, 50 percent within two
weeks, 73 percent within four weeks, and 81 percent by four weeks or longer [178].
Resolution was quicker in larger (main and lobar) pulmonary arteries compared with
smaller (segmental and subsegmental) vessels, particularly during the first week.

• Another cohort of 111 patients with acute PE reported similar results, but thrombus
resolved more quickly in peripheral compared with larger pulmonary arteries [179].

Differential diagnosis and management of suspected recurrence is 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'.)

DIAGNOSIS

A diagnosis of PE is made radiographically by one of the following modalities using the

following criteria:

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● CT pulmonary angiography (CTPA) or magnetic resonance pulmonary angiography

(MRPA) – A filling defect in any branch of the pulmonary artery (main, lobar, segmental,
subsegmental) that becomes evident after contrast enhancement is diagnostic of PE
( image 5 and image 6) [121]. Indeterminate or nondiagnostic scans are reported
when a filling defect is not clearly visualized (eg, embolus in a small peripheral pulmonary
artery, poor contrast enhancement, image degradation by motion or metallic beam
hardening artefact). (See 'Computed tomography pulmonary angiography' above and
'Magnetic resonance pulmonary angiography' above.)

● Ventilation perfusion (V/Q) scanning – A segmental or subsegmental perfusion defect

with normal ventilation are diagnostic of PE. Images are interpreted as high, intermediate,
or low probability of PE or normal. A normal scan and a low probability scan in the setting
of low clinical probability of PE are sufficient to exclude PE. A high-probability V/Q scan and
high probability of PE confirms PE. All other combinations of V/Q results and clinical
probability are nondiagnostic. Practice guidelines regarding the performance and
interpretation of V/Q scans are available at the Society of Nuclear Medicine on lung
scintigraphy [180]. (See 'Ventilation perfusion scan' above.)

● Catheter-based pulmonary angiography – The demonstration of a filling defect or

abrupt cutoff of a vessel is diagnostic of an embolus ( image 4). Indeterminate or
nondiagnostic scans are reported when the filling defect is not clearly visualized. (See
'Catheter-based pulmonary angiography' above.)

Echocardiography is rarely diagnostic of PE but a presumptive diagnosis may be made in

patients who are hemodynamically unstable so that life-saving therapy can be administered.
(See 'Echocardiography' above and 'Hemodynamically unstable patients' above.)

Lower-extremity proximal vein compressive ultrasound (US) demonstrating deep venous

thrombosis (DVT) is not diagnostic of PE but can be used to justify treatment in emergent
settings or when other testing cannot be obtained. (See 'Lower-extremity ultrasound with
Doppler' above.)

PE is sometimes seen on a standard contrast-enhanced CT performed for an alternate reason or

discovered pathologically in a resected pulmonary lobe. In these cases, dedicated pulmonary
artery or leg vein imaging to diagnose residual PE or DVT may be indicated.

Once a diagnosis is made, further risk stratification of the patient to determine the prognosis
should be performed. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism
in adults", section on 'Prognosis'.)

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DIFFERENTIAL DIAGNOSIS

For patients who present with signs and symptoms of PE, the major competing diagnoses
include heart failure, pneumonia, myocardial ischemia or infarction, pericarditis, acute
exacerbations of chronic lung disease, pneumothorax, and musculoskeletal pain. CT pulmonary
angiography (CTPA) may identify many of these alternative diagnoses.

The differential diagnosis of PE depends upon the presenting signs and symptoms, many of
which are discussed separately:

● Dyspnea – Dyspnea that is abrupt in onset or disproportionate to the patient's underlying

lung function, or dyspnea that occurs with hypoxemia, hemoptysis, and/or pleuritic chest
pain may favor a diagnosis of PE. (See "Epidemiology and pathogenesis of acute
pulmonary embolism in adults" and "Approach to the patient with dyspnea" and
"Approach to the adult with dyspnea in the emergency department".)

● Chest pain – Acute chest pain, especially pain that is pleuritic in nature, is highly
suspicious for PE, but may also be due to other etiologies such as pneumonia, pericarditis,
pleuritis, and rib fracture.

● Hemoptysis – Hemoptysis that occurs with pleuritic pain and hypoxemia should prompt
consideration of acute PE, but can also be secondary to pneumonia or heart failure (often
frothy and pink). (See "Evaluation of nonlife-threatening hemoptysis in adults".)

● Leg pain and swelling – Unilateral leg swelling should raise the suspicion for PE in
association with deep vein thrombosis (DVT), while bilateral swelling may be more
supportive of heart failure. (See "Clinical presentation and diagnosis of the nonpregnant
adult with suspected deep vein thrombosis of the lower extremity", section on 'Differential
diagnosis'.)

● Syncope – Syncope in patients without a clear precipitant should raise suspicion for PE
[19]. (See "Syncope in adults: Clinical manifestations and initial diagnostic evaluation" and
"Approach to the adult patient with syncope in the emergency department".)

● Hypoxemia – Hypoxemia (partial pressure of oxygen in arterial blood on room air <80
mmHg [10 kPa]) in the setting of a normal chest radiograph, or hypoxemia that is
disproportionate to the chest radiograph appearance, should prompt consideration of PE
as well as the following alternate diagnoses:

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• Other pulmonary vascular diseases (eg, chronic venous thromboembolism, pulmonary

hypertension, anatomic shunt, arteriovenous malformations) (see "Epidemiology,
pathogenesis, clinical manifestations and diagnosis of chronic thromboembolic
pulmonary hypertension" and "Clinical features and diagnosis of pulmonary
hypertension of unclear etiology in adults" and "Pulmonary arteriovenous
malformations: Epidemiology, etiology, and pathology in adults")

• Interstitial lung disease (eg, lymphangioleiomyomatosis, Langerhans cell histiocytosis)

(see "Approach to the adult with interstitial lung disease: Clinical evaluation")

• Congenital heart disease (eg, shunt, septal defect, left ventricular outlet obstruction,
chronic mitral stenosis, Eisenmenger syndrome) (see "Pulmonary hypertension with
congenital heart disease: Clinical manifestations and diagnosis")

• Lower-airway disease (eg, pneumonia, asthma, bronchiectasis, acute or chronic

bronchitis, foreign body aspiration, tracheobronchomalacia) (see "Evaluation of
wheezing illnesses other than asthma in adults")

• Upper-airway disease (eg, paradoxical vocal cord dysfunction, upper-airway obstruction

syndromes, tumors) (see "Inducible laryngeal obstruction (paradoxical vocal fold
motion)" and "Asthma in adolescents and adults: Evaluation and diagnosis", section on
'Clinical features')

• Neuromuscular disease (eg, hypoventilation, drugs, multiple sclerosis, diaphragmatic

paralysis, myasthenia gravis) (see "Respiratory muscle weakness due to neuromuscular
disease: Clinical manifestations and evaluation")

● Tachycardia – Unexplained tachycardia, especially in a patient with risk factors for PE,
should prompt clinicians to consider PE, but can be associated with other diagnoses,
including cardiac arrythmia, sepsis, hypovolemia, drugs, and toxins. (See "Sinus
tachycardia: Evaluation and management".)

● Shock – Unexplained shock should prompt the clinician to consider acute PE. Although the
presence of shock and a normal chest radiograph increases the suspicion for PE, this can
be found in many forms of distributive shock (eg, anaphylaxis, shock from drugs and
toxins, neurogenic shock, myxedema coma). (See "Evaluation of and initial approach to the
adult patient with undifferentiated hypotension and shock", section on 'Differential
diagnosis'.)

The differential diagnosis of common conditions that mimic PE include the following:

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● Heart failure – The combination of dyspnea and leg swelling due to heart failure may
mimic PE. Evidence of pulmonary edema may be supported by crackles and chest
radiography. While brain natriuretic peptide elevation can support heart failure, this can
also be seen in acute PE. (See "Heart failure with preserved ejection fraction: Clinical
manifestations and diagnosis".)

● Pneumonia – Fever, consolidation on chest imaging, and leukocytosis may favor infection
over PE, but can also be the presenting features of an acute lobar pulmonary infarct
secondary to PE, particularly as it evolves over the first few days or weeks. The presence of
risk factors for PE, persisting symptoms or poor response to antibiotics, or abrupt onset of
new symptoms during the course of subacute illness should prompt the clinician to
investigate for PE. (See "Clinical evaluation and diagnostic testing for community-acquired
pneumonia in adults" and "Epidemiology, pathogenesis, and microbiology of community-
acquired pneumonia in adults" and "Nonresolving pneumonia".)

● Myocardial ischemia or infarction – Cardiac chest pain is typically not pleuritic and
evidence of myocardial ischemia or infarction can be seen on electrocardiography (ECG).
While troponin elevation can suggest cardiac chest pain, this can also be seen in acute PE.
(See "Diagnosis of acute myocardial infarction".)

● Pericarditis – The pain of pericarditis can be pleuritic and therefore mimic PE. The
presence of a viral prodrome, pre-existing inflammatory disease, and electrocardiographic
findings of ST elevation may increase the likelihood of pericarditis. (See "Acute pericarditis:
Clinical presentation and diagnosis".)

● Exacerbation of underlying chronic lung disease – Patients with chronic lung disease
often present with dyspnea. Conversely, PE can complicate acute pulmonary diseases
illness (eg, emphysema, pneumonia). Thus, the presence of another diagnosis does not
completely exclude the possibility of PE. Wheezing is uncommon in PE, and may suggest
an exacerbation of pre-existing lung disease such as asthma or chronic obstructive
pulmonary disease. However, hypoxemia or respiratory distress out of proportion to
obstructive symptoms or wheezing should prompt consideration of PE. (See "COPD
exacerbations: Management".)

● Pneumothorax – While acute pleuritic chest pain and dyspnea due to pneumothorax may
mimic PE, pneumothorax should be apparent on chest imaging. (See "Pneumothorax in
adults: Epidemiology and etiology" and "Treatment of secondary spontaneous
pneumothorax in adults".)

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● Vasculitis – Unexplained dyspnea, pleuritis, and hemoptysis can be presenting symptoms

of both PE and pulmonary vasculitis. The presence of an interstitial pattern on chest
radiograph in a patient with an underlying rheumatologic condition (eg, scleroderma) may
distinguish vasculitis from PE. (See "Overview of and approach to the vasculitides in
adults", section on 'Differential diagnosis'.)

● Musculoskeletal pain – Acute chest wall pain may mimic the pleuritic pain of PE.
However, in the absence of a clear history of injury, musculoskeletal pain should be
considered a diagnosis of exclusion when PE remains on the differential diagnosis. (See
"Evaluation of the adult with chest pain in the emergency department".)

COVID-19

Coronavirus disease 2019 (COVID-19) is a risk factor for the development of thrombosis. Details
regarding hypercoagulability in patients with COVID-19 are provided separately. (See "COVID-19:
Hypercoagulability".)

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.)

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

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

SUMMARY AND RECOMMENDATIONS

● Clinical features – 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 but not always pleuritic) and cough.
However, many patients, including those with large PE, have mild symptoms or are
asymptomatic. (See 'Clinical presentation' above.)

● Initial tests – In patients with symptoms consistent with PE, tests including
electrocardiography (ECG), chest radiography, brain natriuretic peptide (BNP) and troponin
levels should be performed. However, these tests are neither sensitive nor specific for the
diagnosis of PE, and are most useful for confirming the presence of alternative diagnoses
or providing prognostic information in the event that PE is diagnosed. (See 'Laboratory
tests' above and 'Electrocardiography' above and 'Chest radiograph' above.)

● Hemodynamically unstable patients – (See 'Hemodynamically unstable patients' above.)

• For patients with a high clinical suspicion for PE who are hemodynamically unstable
and successfully resuscitated, immediate anticoagulation and definitive diagnostic
imaging is preferred. (See 'Hemodynamic stability restored following resuscitation'
above.)

• For patients with a low or moderate suspicion of PE who are successfully resuscitated,
the same approach to diagnosis and empiric anticoagulation should be used as for
patients who are hemodynamically stable. (See 'Hemodynamically stable patients'
above.)

• For patients who remain unstable despite resuscitation, bedside echocardiography and
lower extremity compression ultrasonography (US) with Doppler of the leg veins can be
used to obtain a rapid or presumptive diagnosis of PE (visualization of thrombus or
new right heart strain) to justify the administration of potentially life-saving therapies,
including thrombolytic agents. (See 'Hemodynamically unstable patients' above and
'Electrocardiography' above.)

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(Related Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are

hemodynamically unstable despite resuscitative efforts.)

● Hemodynamically stable patients – For patients with suspected PE who are

hemodynamically stable, we suggest an approach that selectively integrates clinical
evaluation, three-tiered pretest probability testing (eg, clinical gestalt or the Wells criteria
( table 2) (calculator 1)), PE rule out criteria (PERC) (calculator 3), D-dimer, and imaging.
CT pulmonary angiography (CTPA), also called chest CT angiogram with contrast, is the
preferred imaging exam ( algorithm 1 and algorithm 2 and algorithm 3) (see
'Hemodynamically stable patients' above):

• In patients with a low clinical probability of PE (eg, <15 percent, Wells score <2), the
PERC ( table 4) should be applied. Patients who fulfill all eight criteria do not need
additional testing. For patients who do not fulfill PERC criteria or in whom PERC cannot
be applied, further testing with sensitive D-dimer measurement is indicated; no
imaging is required when the D-dimer level is normal (<500 ng/mL [fibrinogen
equivalent units]), while imaging is indicated in those with a positive D-dimer. (See 'Low
probability of pulmonary embolism' above.)

A positive D-dimer can be defined as ≥500 ng/mL (fibrinogen equivalent units) or a

value higher than the age-adjusted or pretest probability adjusted (eg, YEARS)
threshold. Adjusted D-dimer levels based on certain criteria have been proposed and
may be considered as an alternative in patients with a low probability (or low
intermediate probability for PE). They should not be used in those with high-probability
or intermediate-high-probability for PE. (See 'Adjusted D-dimer' above.)

• In patients with an intermediate clinical probability of PE (eg, Wells score 2 to 6), we

prefer sensitive D-dimer testing to determine whether or not diagnostic imaging is
indicated. Patients with a negative D-dimer do not need imaging while those with a
positive D-dimer should have chest imaging. However, some experts proceed directly
to diagnostic imaging in select patients (eg, those with limited cardiopulmonary
reserve or those in the upper zone of the intermediate range such as a Wells score of 4
to 6). (See 'Intermediate probability of pulmonary embolism' above.)

• In patients with a high clinical probability of PE (eg, Wells score >6), we prefer
diagnostic imaging with CTPA. A positive result confirms the diagnosis of PE while a
negative result excludes it in nearly all cases. (See 'High probability of pulmonary
embolism' above and 'Computed tomography pulmonary angiography' above.)

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CTPA acquires thin (≤2.5 mm) section volumetric images of the chest after a bolus
administration of intravenous contrast that is timed precisely for maximal
enhancement of the pulmonary arteries. A multidetector row (≥16 detectors rows) CT
scanner is required to achieve sufficient diagnostic performance. A chest CT with
contrast not performed as a CTPA but for other indications is not an adequate exam to
exclude suspected PE. (See 'CTPA imaging protocol' above.)

(Related Pathway(s): Pulmonary embolism: Diagnostic evaluation in adults who are

hemodynamically stable.)

● Alternate imaging approaches

• Ventilation perfusion (V/Q) scanning – For patients with suspected PE in whom CTPA is
contraindicated, unavailable, or inconclusive, V/Q scanning is the alternative imaging
exam. V/Q scan results, reported as high-, intermediate-, or low-probability for PE, or
normal, should be interpreted in conjunction with clinical suspicion. A high-probability
V/Q scan and high clinical probability is sufficient to confirm PE. A normal scan or a low-
probability scan in the setting of low clinical probability of PE can also be used to rule
out PE. All other combinations of V/Q results and clinical probability are nondiagnostic.
(See 'Hemodynamically stable patients' above and 'Ventilation perfusion scan' above.)

• Other testing – For patients in whom both CTPA and V/Q scanning are contraindicated,
unavailable, or inconclusive, we prefer noninvasive testing with lower-extremity
compression ultrasonography with Doppler (although not diagnostic of PE). (See
'Lower-extremity ultrasound with Doppler' above.)

● Diagnosis – A diagnosis of PE is made radiographically based upon CTPA, magnetic

resonance pulmonary angiogram (MRPA), or catheter-based pulmonary angiography by
the demonstration of a filling defect in any branch of the pulmonary artery. With V/Q
scanning, a high-probability scan with high clinical probability confirms PE. (See 'Diagnosis'
above.)

● Differential diagnosis – The differential diagnosis of PE includes many other entities that
present similarly with dyspnea, chest pain, hypoxemia, leg pain and swelling, tachycardia,
syncope, and shock. Other competing diagnoses including heart failure, myocardial
ischemia, pneumothorax, pneumonia, and pericarditis may be distinguished on
electrocardiographic, echocardiographic, laboratory, and chest radiographic testing.
However, PE can coexist with these conditions and, therefore, the presence of an alternate
diagnosis does not completely exclude the diagnosis of PE. (See 'Differential diagnosis'
above.)
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ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges Charles Hales, MD, now deceased, who contributed
to earlier versions of this topic review.

Use of UpToDate is subject to the Terms of Use.

REFERENCES

1. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and
management of acute pulmonary embolism developed in collaboration with the European
Respiratory Society (ERS): The Task Force for the diagnosis and management of acute
pulmonary embolism of the European Society of Cardiology (ESC). Eur Respir J 2019; 54.
2. Raja AS, Greenberg JO, Qaseem A, et al. Evaluation of Patients With Suspected Acute
Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the
American College of Physicians. Ann Intern Med 2015; 163:701.
3. Lim W, Le Gal G, Bates SM, et al. American Society of Hematology 2018 guidelines for
management of venous thromboembolism: diagnosis of venous thromboembolism. Blood
Adv 2018; 2:3226.
4. American College of Emergency Physicians Clinical Policies Subcommittee (Writing
Committee) on Thromboembolic Disease:, Wolf SJ, Hahn SA, et al. Clinical Policy: Critical
Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency
Department With Suspected Acute Venous Thromboembolic Disease. Ann Emerg Med
2018; 71:e59.
5. Expert Panel on Cardiac Imaging, Kirsch J, Wu CC, et al. ACR Appropriateness Criteria®
Suspected Pulmonary Embolism: 2022 Update. J Am Coll Radiol 2022; 19:S488.
6. PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary
embolism. Results of the prospective investigation of pulmonary embolism diagnosis
(PIOPED). JAMA 1990; 263:2753.
7. Stein PD, Terrin ML, Hales CA, et al. Clinical, laboratory, roentgenographic, and
electrocardiographic findings in patients with acute pulmonary embolism and no pre-
existing cardiac or pulmonary disease. Chest 1991; 100:598.
8. Stein PD, Saltzman HA, Weg JG. Clinical characteristics of patients with acute pulmonary
embolism. Am J Cardiol 1991; 68:1723.

https://www.uptodate.com/contents/8261/print 36/69
2/17/24, 8:28 PM 8261

9. Stein PD, Beemath A, Matta F, et al. Clinical characteristics of patients with acute pulmonary
embolism: data from PIOPED II. Am J Med 2007; 120:871.
10. Lucassen W, Geersing GJ, Erkens PM, et al. Clinical decision rules for excluding pulmonary
embolism: a meta-analysis. Ann Intern Med 2011; 155:448.
11. Liesching T, O'Brien A. Significance of a syncopal event. Pulmonary embolism. Postgrad
Med 2002; 111:19.
12. Castelli R, Tarsia P, Tantardini C, et al. Syncope in patients with pulmonary embolism:
comparison between patients with syncope as the presenting symptom of pulmonary
embolism and patients with pulmonary embolism without syncope. Vasc Med 2003; 8:257.
13. Coen M, Leuchter I, Sussetto M, et al. Progressive Dysphonia: Ortner Syndrome. Am J Med
2018; 131:e494.
14. Blanc JJ, L'Her C, Touiza A, et al. Prospective evaluation and outcome of patients admitted
for syncope over a 1 year period. Eur Heart J 2002; 23:815.
15. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med
2002; 347:878.

16. Vanbrabant P, Van Ouytsel V, Knockaert D, Gillet JB. Diagnostic yield of syncope
investigation (initiated) in the emergency department: a pilot study. Acta Clin Belg 2011;
66:110.
17. Saravi M, Ahmadi Ahangar A, Hojati MM, et al. Etiology of syncope in hospitalized patients.
Caspian J Intern Med 2015; 6:233.

18. Keller K, Beule J, Balzer JO, Dippold W. Syncope and collapse in acute pulmonary embolism.
Am J Emerg Med 2016; 34:1251.
19. Prandoni P, Lensing AW, Prins MH, et al. Prevalence of Pulmonary Embolism among
Patients Hospitalized for Syncope. N Engl J Med 2016; 375:1524.

20. Verma AA, Masoom H, Rawal S, et al. Pulmonary Embolism and Deep Venous Thrombosis in
Patients Hospitalized With Syncope: A Multicenter Cross-sectional Study in Toronto,
Ontario, Canada. JAMA Intern Med 2017; 177:1046.
21. Costantino G, Ruwald MH, Quinn J, et al. Prevalence of Pulmonary Embolism in Patients
With Syncope. JAMA Intern Med 2018; 178:356.
22. Badertscher P, du Fay de Lavallaz J, Hammerer-Lercher A, et al. Prevalence of Pulmonary
Embolism in Patients With Syncope. J Am Coll Cardiol 2019; 74:744.
23. den Exter PL, van Es J, Erkens PM, et al. Impact of delay in clinical presentation on the
diagnostic management and prognosis of patients with suspected pulmonary embolism.
Am J Respir Crit Care Med 2013; 187:1369.
https://www.uptodate.com/contents/8261/print 37/69
2/17/24, 8:28 PM 8261

24. Stein PD, Matta F, Musani MH, Diaczok B. Silent pulmonary embolism in patients with deep
venous thrombosis: a systematic review. Am J Med 2010; 123:426.
25. Courtney DM, Sasser HC, Pincus CL, Kline JA. Pulseless electrical activity with witnessed
arrest as a predictor of sudden death from massive pulmonary embolism in outpatients.
Resuscitation 2001; 49:265.
26. Courtney DM, Kline JA. Prospective use of a clinical decision rule to identify pulmonary
embolism as likely cause of outpatient cardiac arrest. Resuscitation 2005; 65:57.

27. Guidelines on diagnosis and management of acute pulmonary embolism. Task Force on
Pulmonary Embolism, European Society of Cardiology. Eur Heart J 2000; 21:1301.
28. Kucher N, Goldhaber SZ. Management of massive pulmonary embolism. Circulation 2005;
112:e28.
29. Stein PD, Goldhaber SZ, Henry JW, Miller AC. Arterial blood gas analysis in the assessment
of suspected acute pulmonary embolism. Chest 1996; 109:78.
30. Rodger MA, Carrier M, Jones GN, et al. Diagnostic value of arterial blood gas measurement
in suspected pulmonary embolism. Am J Respir Crit Care Med 2000; 162:2105.
31. Stein PD, Goldhaber SZ, Henry JW. Alveolar-arterial oxygen gradient in the assessment of
acute pulmonary embolism. Chest 1995; 107:139.

32. Kline JA, Hernandez-Nino J, Newgard CD, et al. Use of pulse oximetry to predict in-hospital
complications in normotensive patients with pulmonary embolism. Am J Med 2003;
115:203.

33. Söhne M, Ten Wolde M, Boomsma F, et al. Brain natriuretic peptide in hemodynamically
stable acute pulmonary embolism. J Thromb Haemost 2006; 4:552.
34. Kiely DG, Kennedy NS, Pirzada O, et al. Elevated levels of natriuretic peptides in patients
with pulmonary thromboembolism. Respir Med 2005; 99:1286.
35. Meyer T, Binder L, Hruska N, et al. Cardiac troponin I elevation in acute pulmonary
embolism is associated with right ventricular dysfunction. J Am Coll Cardiol 2000; 36:1632.

36. Giannitsis E, Müller-Bardorff M, Kurowski V, et al. Independent prognostic value of cardiac

troponin T in patients with confirmed pulmonary embolism. Circulation 2000; 102:211.
37. Pruszczyk P, Bochowicz A, Torbicki A, et al. Cardiac troponin T monitoring identifies high-
risk group of normotensive patients with acute pulmonary embolism. Chest 2003;
123:1947.
38. Konstantinides S, Geibel A, Olschewski M, et al. Importance of cardiac troponins I and T in
risk stratification of patients with acute pulmonary embolism. Circulation 2002; 106:1263.

https://www.uptodate.com/contents/8261/print 38/69
2/17/24, 8:28 PM 8261

39. Douketis JD, Crowther MA, Stanton EB, Ginsberg JS. Elevated cardiac troponin levels in
patients with submassive pulmonary embolism. Arch Intern Med 2002; 162:79.
40. Horlander KT, Leeper KV. Troponin levels as a guide to treatment of pulmonary embolism.
Curr Opin Pulm Med 2003; 9:374.
41. Müller-Bardorff M, Weidtmann B, Giannitsis E, et al. Release kinetics of cardiac troponin T in
survivors of confirmed severe pulmonary embolism. Clin Chem 2002; 48:673.
42. Geibel A, Zehender M, Kasper W, et al. Prognostic value of the ECG on admission in patients
with acute major pulmonary embolism. Eur Respir J 2005; 25:843.
43. Ferrari E, Imbert A, Chevalier T, et al. The ECG in pulmonary embolism. Predictive value of
negative T waves in precordial leads--80 case reports. Chest 1997; 111:537.
44. Rodger M, Makropoulos D, Turek M, et al. Diagnostic value of the electrocardiogram in
suspected pulmonary embolism. Am J Cardiol 2000; 86:807.

45. Shopp JD, Stewart LK, Emmett TW, Kline JA. Findings From 12-lead Electrocardiography That
Predict Circulatory Shock From Pulmonary Embolism: Systematic Review and Meta-analysis.
Acad Emerg Med 2015; 22:1127.
46. Co I, Eilbert W, Chiganos T. New Electrocardiographic Changes in Patients Diagnosed with
Pulmonary Embolism. J Emerg Med 2017; 52:280.
47. Panos RJ, Barish RA, Whye DW Jr, Groleau G. The electrocardiographic manifestations of
pulmonary embolism. J Emerg Med 1988; 6:301.
48. Thames MD, Alpert JS, Dalen JE. Syncope in patients with pulmonary embolism. JAMA 1977;
238:2509.
49. Elliott CG, Goldhaber SZ, Visani L, DeRosa M. Chest radiographs in acute pulmonary
embolism. Results from the International Cooperative Pulmonary Embolism Registry. Chest
2000; 118:33.
50. Worsley DF, Alavi A, Aronchick JM, et al. Chest radiographic findings in patients with acute
pulmonary embolism: observations from the PIOPED Study. Radiology 1993; 189:133.
51. Anbalagan LC, Khanna K, Aggarwal R, et al. Acute pulmonary embolism and Palla's sign.
QJM 2021; 114:669.

52. Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive
pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic
pulmonary hypertension: a scientific statement from the American Heart Association.
Circulation 2011; 123:1788.

53. Sista AK, Kuo WT, Schiebler M, Madoff DC. Stratification, Imaging, and Management of
Acute Massive and Submassive Pulmonary Embolism. Radiology 2017; 284:5.
https://www.uptodate.com/contents/8261/print 39/69
2/17/24, 8:28 PM 8261

54. Afonso L, Sood A, Akintoye E, et al. A Doppler Echocardiographic Pulmonary Flow Marker of
Massive or Submassive Acute Pulmonary Embolus. J Am Soc Echocardiogr 2019; 32:799.
55. Kabrhel C, Jaff MR, Channick RN, et al. A multidisciplinary pulmonary embolism response
team. Chest 2013; 144:1738.
56. Dudzinski DM, Piazza G. Multidisciplinary Pulmonary Embolism Response Teams.
Circulation 2016; 133:98.
57. Kabrhel C, Rosovsky R, Channick R, et al. A Multidisciplinary Pulmonary Embolism Response
Team: Initial 30-Month Experience With a Novel Approach to Delivery of Care to Patients
With Submassive and Massive Pulmonary Embolism. Chest 2016; 150:384.
58. van Belle A, Büller 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.
59. Klok FA, Mos IC, Nijkeuter M, et al. Simplification of the revised Geneva score for assessing
clinical probability of pulmonary embolism. Arch Intern Med 2008; 168:2131.
60. Wells PS, Ginsberg JS, Anderson DR, et al. Use of a clinical model for safe management of
patients with suspected pulmonary embolism. Ann Intern Med 1998; 129:997.
61. Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside
without diagnostic imaging: management of patients with suspected pulmonary embolism
presenting to the emergency department by using a simple clinical model and d-dimer.
Ann Intern Med 2001; 135:98.

62. Klok FA, Kruisman E, Spaan J, et al. Comparison of the revised Geneva score with the Wells
rule for assessing clinical probability of pulmonary embolism. J Thromb Haemost 2008;
6:40.
63. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out
pulmonary embolism: the ADJUST-PE study. JAMA 2014; 311:1117.
64. Jiménez D, Resano S, Otero R, et al. Computerised clinical decision support for suspected
PE. Thorax 2015; 70:909.
65. Roussel M, Bloom B, Taalba M, et al. Temporal Trends in the Use of Computed Tomographic
Pulmonary Angiography for Suspected Pulmonary Embolism in the Emergency Department
: A Retrospective Analysis. Ann Intern Med 2023; 176:761.
66. Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United
States: evidence of overdiagnosis. Arch Intern Med 2011; 171:831.

67. Feng LB, Pines JM, Yusuf HR, Grosse SD. U.S. trends in computed tomography use and
diagnoses in emergency department visits by patients with symptoms suggestive of

https://www.uptodate.com/contents/8261/print 40/69
2/17/24, 8:28 PM 8261

pulmonary embolism, 2001-2009. Acad Emerg Med 2013; 20:1033.

68. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency
department: the revised Geneva score. Ann Intern Med 2006; 144:165.
69. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize
patients probability of pulmonary embolism: increasing the models utility with the
SimpliRED D-dimer. Thromb Haemost 2000; 83:416.
70. Kline JA, Stubblefield WB. Clinician gestalt estimate of pretest probability for acute coronary
syndrome and pulmonary embolism in patients with chest pain and dyspnea. Ann Emerg
Med 2014; 63:275.
71. Schouten HJ, Geersing GJ, Oudega R, et al. Accuracy of the Wells clinical prediction rule for
pulmonary embolism in older ambulatory adults. J Am Geriatr Soc 2014; 62:2136.
72. Hendriksen JM, Geersing GJ, Lucassen WA, et al. Diagnostic prediction models for
suspected pulmonary embolism: systematic review and independent external validation in
primary care. BMJ 2015; 351:h4438.
73. Hendriksen JM, Lucassen WA, Erkens PM, et al. Ruling Out Pulmonary Embolism in Primary
Care: Comparison of the Diagnostic Performance of "Gestalt" and the Wells Rule. Ann Fam
Med 2016; 14:227.
74. Wang RC, Bent S, Weber E, et al. The Impact of Clinical Decision Rules on Computed
Tomography Use and Yield for Pulmonary Embolism: A Systematic Review and Meta-
analysis. Ann Emerg Med 2016; 67:693.

75. Newnham M, Stone H, Summerfield R, Mustfa N. Performance of algorithms and pre-test

probability scores is often overlooked in the diagnosis of pulmonary embolism. BMJ 2013;
346:f1557.
76. Hsu N, Soo Hoo GW. Underuse of Clinical Decision Rules and d-Dimer in Suspected
Pulmonary Embolism: A Nationwide Survey of the Veterans Administration Healthcare
System. J Am Coll Radiol 2020; 17:405.
77. Girardi AM, Bettiol RS, Garcia TS, et al. Wells and Geneva Scores Are Not Reliable Predictors
of Pulmonary Embolism in Critically Ill Patients: A Retrospective Study. J Intensive Care Med
2020; 35:1112.
78. Bass AR, Fields KG, Goto R, et al. Clinical Decision Rules for Pulmonary Embolism in
Hospitalized Patients: A Systematic Literature Review and Meta-analysis. Thromb Haemost
2017; 117:2176.

79. Abdelaal Ahmed Mahmoud M Alkhatip A, Donnelly M, Snyman L, et al. YEARS Algorithm
Versus Wells' Score: Predictive Accuracies in Pulmonary Embolism Based on the Gold

https://www.uptodate.com/contents/8261/print 41/69
2/17/24, 8:28 PM 8261

Standard CT Pulmonary Angiography. Crit Care Med 2020; 48:704.

80. Kline JA, Courtney DM, Kabrhel C, et al. Prospective multicenter evaluation of the
pulmonary embolism rule-out criteria. J Thromb Haemost 2008; 6:772.
81. Hugli O, Righini M, Le Gal G, et al. The pulmonary embolism rule-out criteria (PERC) rule
does not safely exclude pulmonary embolism. J Thromb Haemost 2011; 9:300.
82. Singh B, Mommer SK, Erwin PJ, et al. Pulmonary embolism rule-out criteria (PERC) in
pulmonary embolism--revisited: a systematic review and meta-analysis. Emerg Med J 2013;
30:701.
83. Truong P, Mazzolai L, Font C, et al. Safety of the pulmonary embolism rule-out criteria rule:
Findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa
(RIETE) registry. Acad Emerg Med 2023; 30:935.
84. Freund Y, Cachanado M, Aubry A, et al. Effect of the Pulmonary Embolism Rule-Out Criteria
on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients:
The PROPER Randomized Clinical Trial. JAMA 2018; 319:559.
85. Wolf SJ, McCubbin TR, Nordenholz KE, et al. Assessment of the pulmonary embolism rule-
out criteria rule for evaluation of suspected pulmonary embolism in the emergency
department. Am J Emerg Med 2008; 26:181.
86. Le Gal G, Righini M, Roy PM, et al. Value of D-dimer testing for the exclusion of pulmonary
embolism in patients with previous venous thromboembolism. Arch Intern Med 2006;
166:176.

87. Stein PD, Hull RD, Patel KC, et al. D-dimer for the exclusion of acute venous thrombosis and
pulmonary embolism: a systematic review. Ann Intern Med 2004; 140:589.
88. Stein PD, Woodard PK, Weg JG, et al. Diagnostic pathways in acute pulmonary embolism:
recommendations of the PIOPED II investigators. Am J Med 2006; 119:1048.
89. Kearon C, Ginsberg JS, Douketis J, et al. An evaluation of D-dimer in the diagnosis of
pulmonary embolism: a randomized trial. Ann Intern Med 2006; 144:812.
90. Righini M, Le Gal G, Aujesky D, et al. Diagnosis of pulmonary embolism by multidetector CT
alone or combined with venous ultrasonography of the leg: a randomised non-inferiority
trial. Lancet 2008; 371:1343.
91. Crawford F, Andras A, Welch K, et al. D-dimer test for excluding the diagnosis of pulmonary
embolism. Cochrane Database Syst Rev 2016; :CD010864.
92. Geersing GJ, Janssen KJ, Oudega R, et al. Excluding venous thromboembolism using point
of care D-dimer tests in outpatients: a diagnostic meta-analysis. BMJ 2009; 339:b2990.

https://www.uptodate.com/contents/8261/print 42/69
2/17/24, 8:28 PM 8261

93. De Monyé W, Sanson BJ, Mac Gillavry MR, et al. Embolus location affects the sensitivity of a
rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism. Am J Respir Crit
Care Med 2002; 165:345.
94. Crowther MA, Cook DJ, Griffith LE, et al. Neither baseline tests of molecular
hypercoagulability nor D-dimer levels predict deep venous thrombosis in critically ill
medical-surgical patients. Intensive Care Med 2005; 31:48.

95. Rathbun SW, Whitsett TL, Vesely SK, Raskob GE. Clinical utility of D-dimer in patients with
suspected pulmonary embolism and nondiagnostic lung scans or negative CT findings.
Chest 2004; 125:851.
96. Karami-Djurabi R, Klok FA, Kooiman J, et al. D-dimer testing in patients with suspected
pulmonary embolism and impaired renal function. Am J Med 2009; 122:1050.
97. Righini M, Goehring C, Bounameaux H, Perrier A. Effects of age on the performance of
common diagnostic tests for pulmonary embolism. Am J Med 2000; 109:357.
98. Kabrhel C, Mark Courtney D, Camargo CA Jr, et al. Factors associated with positive D-dimer
results in patients evaluated for pulmonary embolism. Acad Emerg Med 2010; 17:589.
99. Woller SC, Stevens SM, Adams DM, et al. Assessment of the safety and efficiency of using
an age-adjusted D-dimer threshold to exclude suspected pulmonary embolism. Chest 2014;
146:1444.
100. Douma RA, le Gal G, Söhne M, et al. Potential of an age adjusted D-dimer cut-off value to
improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of
three large cohorts. BMJ 2010; 340:c1475.

101. Sharp AL, Vinson DR, Alamshaw F, et al. An Age-Adjusted D-dimer Threshold for Emergency
Department Patients With Suspected Pulmonary Embolus: Accuracy and Clinical
Implications. Ann Emerg Med 2016; 67:249.
102. Fuchs E, Asakly S, Karban A, Tzoran I. Age-Adjusted Cutoff D-Dimer Level to Rule Out Acute
Pulmonary Embolism: A Validation Cohort Study. Am J Med 2016; 129:872.
103. van Es N, van der Hulle T, van Es J, et al. Wells Rule and d-Dimer Testing to Rule Out
Pulmonary Embolism: A Systematic Review and Individual-Patient Data Meta-analysis. Ann
Intern Med 2016; 165:253.
104. Farm M, Siddiqui AJ, Onelöv L, et al. Age-adjusted D-dimer cut-off leads to more efficient
diagnosis of venous thromboembolism in the emergency department: a comparison of
four assays. J Thromb Haemost 2018; 16:866.

105. van der Hulle T, Cheung WY, Kooij S, et al. Simplified diagnostic management of suspected
pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet

https://www.uptodate.com/contents/8261/print 43/69
2/17/24, 8:28 PM 8261

2017; 390:289.
106. van der Pol LM, van der Hulle T, Cheung YW, et al. No added value of the age-adjusted D-
dimer cut-off to the YEARS algorithm in patients with suspected pulmonary embolism. J
Thromb Haemost 2017; 15:2317.
107. Kabrhel C, Van Hylckama Vlieg A, Muzikanski A, et al. Multicenter Evaluation of the YEARS
Criteria in Emergency Department Patients Evaluated for Pulmonary Embolism. Acad
Emerg Med 2018; 25:987.

108. Eddy M, Robert-Ebadi H, Richardson L, et al. External validation of the YEARS diagnostic
algorithm for suspected pulmonary embolism. J Thromb Haemost 2020; 18:3289.

109. Kearon C, de Wit K, Parpia S, et al. Diagnosis of Pulmonary Embolism with d-Dimer
Adjusted to Clinical Probability. N Engl J Med 2019; 381:2125.
110. Freund Y, Chauvin A, Jimenez S, et al. Effect of a Diagnostic Strategy Using an Elevated and
Age-Adjusted D-Dimer Threshold on Thromboembolic Events in Emergency Department
Patients With Suspected Pulmonary Embolism: A Randomized Clinical Trial. JAMA 2021;
326:2141.

111. Stals MAM, Takada T, Kraaijpoel N, et al. Safety and Efficiency of Diagnostic Strategies for
Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups : A Systematic
Review and Individual-Patient Data Meta-analysis. Ann Intern Med 2022; 175:244.
112. Wittram C. How I do it: CT pulmonary angiography. AJR Am J Roentgenol 2007; 188:1255.
113. Remy-Jardin M, Pistolesi M, Goodman LR, et al. Management of suspected acute pulmonary
embolism in the era of CT angiography: a statement from the Fleischner Society. Radiology
2007; 245:315.
114. Kalva SP, Jagannathan JP, Hahn PF, Wicky ST. Venous thromboembolism: indirect CT
venography during CT pulmonary angiography--should the pelvis be imaged? Radiology
2008; 246:605.
115. Hunsaker AR, Zou KH, Poh AC, et al. Routine pelvic and lower extremity CT venography in
patients undergoing pulmonary CT angiography. AJR Am J Roentgenol 2008; 190:322.
116. Eng J, Krishnan JA, Segal JB, et al. Accuracy of CT in the diagnosis of pulmonary embolism: a
systematic literature review. AJR Am J Roentgenol 2004; 183:1819.
117. Rathbun SW, Raskob GE, Whitsett TL. Sensitivity and specificity of helical computed
tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med
2000; 132:227.

118. Mullins MD, Becker DM, Hagspiel KD, Philbrick JT. The role of spiral volumetric computed
tomography in the diagnosis of pulmonary embolism. Arch Intern Med 2000; 160:293.

https://www.uptodate.com/contents/8261/print 44/69
2/17/24, 8:28 PM 8261

119. Qanadli SD, Hajjam ME, Mesurolle B, et al. Pulmonary embolism detection: prospective
evaluation of dual-section helical CT versus selective pulmonary arteriography in 157
patients. Radiology 2000; 217:447.
120. Courtney DM, Miller C, Smithline H, et al. Prospective multicenter assessment of
interobserver agreement for radiologist interpretation of multidetector computerized
tomographic angiography for pulmonary embolism. J Thromb Haemost 2010; 8:533.
121. Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute
pulmonary embolism. N Engl J Med 2006; 354:2317.
122. Wang L, Kang W, Zu M, et al. Application of 128-slice spiral CT combination scanning in the
diagnosis of embolisms in pulmonary arteries and lower extremity veins. Exp Ther Med
2014; 7:401.
123. Kligerman SJ, Lahiji K, Galvin JR, et al. Missed pulmonary emboli on CT angiography:
assessment with pulmonary embolism-computer-aided detection. AJR Am J Roentgenol
2014; 202:65.
124. Kurcz J, Garcarek J, Guziński M, et al. Multislice computed tomography angiography as an
imaging modality of choice in patients with suspicion of pulmonary embolism - own
experiences and modern imaging techniques. Adv Clin Exp Med 2013; 22:705.
125. Quiroz R, Kucher N, Zou KH, et al. Clinical validity of a negative computed tomography scan
in patients with suspected pulmonary embolism: a systematic review. JAMA 2005; 293:2012.
126. Perrier A, Roy PM, Sanchez O, et al. Multidetector-row computed tomography in suspected
pulmonary embolism. N Engl J Med 2005; 352:1760.
127. Musset D, Parent F, Meyer G, et al. Diagnostic strategy for patients with suspected
pulmonary embolism: a prospective multicentre outcome study. Lancet 2002; 360:1914.
128. Carrier M, Righini M, Wells PS, et al. Subsegmental pulmonary embolism diagnosed by
computed tomography: incidence and clinical implications. A systematic review and meta-
analysis of the management outcome studies. J Thromb Haemost 2010; 8:1716.
129. Anderson DR, Kahn SR, Rodger MA, et al. Computed tomographic pulmonary angiography
vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a
randomized controlled trial. JAMA 2007; 298:2743.
130. Miller WT Jr, Marinari LA, Barbosa E Jr, et al. Small pulmonary artery defects are not reliable
indicators of pulmonary embolism. Ann Am Thorac Soc 2015; 12:1022.
131. Hutchinson BD, Navin P, Marom EM, et al. Overdiagnosis of Pulmonary Embolism by
Pulmonary CT Angiography. AJR Am J Roentgenol 2015; 205:271.

https://www.uptodate.com/contents/8261/print 45/69
2/17/24, 8:28 PM 8261

132. Kim KI, Müller NL, Mayo JR. Clinically suspected pulmonary embolism: utility of spiral CT.
Radiology 1999; 210:693.
133. Garg K, Sieler H, Welsh CH, et al. Clinical validity of helical CT being interpreted as negative
for pulmonary embolism: implications for patient treatment. AJR Am J Roentgenol 1999;
172:1627.
134. Hall WB, Truitt SG, Scheunemann LP, et al. The prevalence of clinically relevant incidental
findings on chest computed tomographic angiograms ordered to diagnose pulmonary
embolism. Arch Intern Med 2009; 169:1961.
135. Perelas A, Dimou A, Saenz A, et al. Incidental findings on computed tomography
angiography in patients evaluated for pulmonary embolism. Ann Am Thorac Soc 2015;
12:689.
136. Cheikh AB, Gorincour G, Nivet H, et al. How artificial intelligence improves radiological
interpretation in suspected pulmonary embolism. Eur Radiol 2022; 32:5831.
137. Langius-Wiffen E, de Jong PA, Mohamed Hoesein FA, et al. Added value of an artificial
intelligence algorithm in reducing the number of missed incidental acute pulmonary
embolism in routine portal venous phase chest CT. Eur Radiol 2024; 34:367.
138. Kruip MJ, Leclercq MG, van der Heul C, et al. Diagnostic strategies for excluding pulmonary
embolism in clinical outcome studies. A systematic review. Ann Intern Med 2003; 138:941.
139. Weinberg AS, Chang W, Ih G, et al. Portable Ventilation/Perfusion Scanning is Useful for
Evaluating Clinically Significant Pulmonary Embolism in the ICU Despite Abnormal Chest
Radiography. J Intensive Care Med 2020; 35:1032.
140. van Rossum AB, van Houwelingen HC, Kieft GJ, Pattynama PM. Prevalence of deep vein
thrombosis in suspected and proven pulmonary embolism: a meta-analysis. Br J Radiol
1998; 71:1260.
141. Falster C, Jacobsen N, Coman KE, et al. Diagnostic accuracy of focused deep venous, lung,
cardiac and multiorgan ultrasound in suspected pulmonary embolism: a systematic review
and meta-analysis. Thorax 2022; 77:679.
142. Hull RD, Raskob GE, Coates G, et al. A new noninvasive management strategy for patients
with suspected pulmonary embolism. Arch Intern Med 1989; 149:2549.
143. Kearon C, Ginsberg JS, Hirsh J. The role of venous ultrasonography in the diagnosis of
suspected deep venous thrombosis and pulmonary embolism. Ann Intern Med 1998;
129:1044.

144. Macklon NS, Greer IA, Bowman AW. An ultrasound study of gestational and postural
changes in the deep venous system of the leg in pregnancy. Br J Obstet Gynaecol 1997;

https://www.uptodate.com/contents/8261/print 46/69
2/17/24, 8:28 PM 8261

104:191.
145. Wittram C, Waltman AC, Shepard JA, et al. Discordance between CT and angiography in the
PIOPED II study. Radiology 2007; 244:883.

146. Stein PD, Henry JW, Gottschalk A. Reassessment of pulmonary angiography for the
diagnosis of pulmonary embolism: relation of interpreter agreement to the order of the
involved pulmonary arterial branch. Radiology 1999; 210:689.
147. Hofmann LV, Lee DS, Gupta A, et al. Safety and hemodynamic effects of pulmonary
angiography in patients with pulmonary hypertension: 10-year single-center experience.
AJR Am J Roentgenol 2004; 183:779.
148. Hudson ER, Smith TP, McDermott VG, et al. Pulmonary angiography performed with
iopamidol: complications in 1,434 patients. Radiology 1996; 198:61.
149. Stein PD, Athanasoulis C, Alavi A, et al. Complications and validity of pulmonary
angiography in acute pulmonary embolism. Circulation 1992; 85:462.
150. Kuiper JW, Geleijns J, Matheijssen NA, et al. Radiation exposure of multi-row detector spiral
computed tomography of the pulmonary arteries: comparison with digital subtraction
pulmonary angiography. Eur Radiol 2003; 13:1496.
151. Resten A, Mausoleo F, Valero M, Musset D. Comparison of doses for pulmonary embolism
detection with helical CT and pulmonary angiography. Eur Radiol 2003; 13:1515.

152. Revel MP, Sanchez O, Couchon S, et al. Diagnostic accuracy of magnetic resonance imaging
for an acute pulmonary embolism: results of the 'IRM-EP' study. J Thromb Haemost 2012;
10:743.
153. Stein PD, Chenevert TL, Fowler SE, et al. Gadolinium-enhanced magnetic resonance
angiography for pulmonary embolism: a multicenter prospective study (PIOPED III). Ann
Intern Med 2010; 152:434.
154. Tapson VF. Pulmonary embolism--new diagnostic approaches. N Engl J Med 1997; 336:1449.
155. Zhang LJ, Luo S, Yeh BM, et al. Diagnostic accuracy of three-dimensional contrast-enhanced
MR angiography at 3-T for acute pulmonary embolism detection: comparison with
multidetector CT angiography. Int J Cardiol 2013; 168:4775.
156. Zhou M, Hu Y, Long X, et al. Diagnostic performance of magnetic resonance imaging
for acute pulmonary embolism: a systematic review and meta-analysis. J Thromb Haemost
2015; 13:1623.
157. Oudkerk M, van Beek EJ, Wielopolski P, et al. Comparison of contrast-enhanced magnetic
resonance angiography and conventional pulmonary angiography for the diagnosis of
pulmonary embolism: a prospective study. Lancet 2002; 359:1643.

https://www.uptodate.com/contents/8261/print 47/69
2/17/24, 8:28 PM 8261

158. Goldhaber SZ. Echocardiography in the management of pulmonary embolism. Ann Intern
Med 2002; 136:691.
159. Grifoni S, Olivotto I, Cecchini P, et al. Short-term clinical outcome of patients with acute
pulmonary embolism, normal blood pressure, and echocardiographic right ventricular
dysfunction. Circulation 2000; 101:2817.
160. Wolfe MW, Lee RT, Feldstein ML, et al. Prognostic significance of right ventricular
hypokinesis and perfusion lung scan defects in pulmonary embolism. Am Heart J 1994;
127:1371.
161. Ribeiro A, Juhlin-Dannfelt A, Brodin LA, et al. Pulmonary embolism: relation between the
degree of right ventricle overload and the extent of perfusion defects. Am Heart J 1998;
135:868.
162. Fields JM, Davis J, Girson L, et al. Transthoracic Echocardiography for Diagnosing
Pulmonary Embolism: A Systematic Review and Meta-Analysis. J Am Soc Echocardiogr 2017;
30:714.
163. Gibson NS, Sohne M, Buller HR. Prognostic value of echocardiography and spiral computed
tomography in patients with pulmonary embolism. Curr Opin Pulm Med 2005; 11:380.
164. Kucher N, Rossi E, De Rosa M, Goldhaber SZ. Prognostic role of echocardiography among
patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or
higher. Arch Intern Med 2005; 165:1777.
165. Come PC. Echocardiographic evaluation of pulmonary embolism and its response to
therapeutic interventions. Chest 1992; 101:151S.
166. McConnell MV, Solomon SD, Rayan ME, et al. Regional right ventricular dysfunction
detected by echocardiography in acute pulmonary embolism. Am J Cardiol 1996; 78:469.
167. Ogren M, Bergqvist D, Eriksson H, et al. Prevalence and risk of pulmonary embolism in
patients with intracardiac thrombosis: a population-based study of 23 796 consecutive
autopsies. Eur Heart J 2005; 26:1108.
168. Torbicki A, Galié N, Covezzoli A, et al. Right heart thrombi in pulmonary embolism: results
from the International Cooperative Pulmonary Embolism Registry. J Am Coll Cardiol 2003;
41:2245.
169. Pontana F, Faivre JB, Remy-Jardin M, et al. Lung perfusion with dual-energy multidetector-
row CT (MDCT): feasibility for the evaluation of acute pulmonary embolism in 117
consecutive patients. Acad Radiol 2008; 15:1494.

170. Lu Y, Lorenzoni A, Fox JJ, et al. Noncontrast perfusion single-photon emission CT/CT
scanning: a new test for the expedited, high-accuracy diagnosis of acute pulmonary

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embolism. Chest 2014; 145:1079.

171. Grüning T, Drake BE. V/Q SPECT in the diagnosis of pulmonary embolism. BMJ 2013;
346:f1555.
172. Gutte H, Mortensen J, Jensen CV, et al. Detection of pulmonary embolism with combined
ventilation-perfusion SPECT and low-dose CT: head-to-head comparison with multidetector
CT angiography. J Nucl Med 2009; 50:1987.

173. Squizzato A, Venturini A, Pelitti V, et al. Diagnostic Accuracy of V/Q and Q SPECT/CT in
Patients with Suspected Acute Pulmonary Embolism: A Systematic Review and Meta-
analysis. Thromb Haemost 2023; 123:700.
174. Nazerian P, Vanni S, Volpicelli G, et al. Accuracy of point-of-care multiorgan ultrasonography
for the diagnosis of pulmonary embolism. Chest 2014; 145:950.
175. Aumiller J, Herth FJ, Krasnik M, Eberhardt R. Endobronchial ultrasound for detecting central
pulmonary emboli: a pilot study. Respiration 2009; 77:298.
176. Segraves JM, Daniels CE. Pulmonary embolus diagnosed by endobronchial ultrasound.
Respir Med Case Rep 2015; 16:104.
177. Şentürk A, Argüder E, Babaoğlu E, et al. Diagnostic imaging of pulmonary embolism using
endobronchial ultrasound. Arch Bronconeumol 2013; 49:268.
178. Stein PD, Yaekoub AY, Matta F, et al. Resolution of pulmonary embolism on CT pulmonary
angiography. AJR Am J Roentgenol 2010; 194:1263.
179. Aghayev A, Furlan A, Patil A, et al. The rate of resolution of clot burden measured by
pulmonary CT angiography in patients with acute pulmonary embolism. AJR Am J
Roentgenol 2013; 200:791.
180. Parker JA, Coleman RE, Grady E, et al. SNM practice guideline for lung scintigraphy 4.0. J
Nucl Med Technol 2012; 40:57.
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GRAPHICS

Symptoms and signs of acute pulmonary embolism

Frequency

Symptom

Dyspnea 73 percent

Pleuritic chest pain 66 percent

Cough 37 percent

Hemoptysis 13 percent

Sign

Tachypnea 70 percent

Rales 51 percent

Tachycardia 30 percent

Fourth heart sound 24 percent

Accentuated pulmonic component of second heart sound 23 percent

Circulatory collapse 8 percent

Prepared with data from:

1. Stein PD, Terrin ML, Hales CA, et al. Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients
with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. Chest 1991; 100:598.
2. Stein PD, Saltzman HA, Weg JG. Clinical characteristics of patients with acute pulmonary embolism. Am J Cardiol 1991;
68:1723.

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Hamptons hump on radiograph and CT scan

Hamptons hump in a patient with suspected pulmonary embolus. An anterior-posterior chest

radiograph (A) shows a wedge-shaped opacity in the lateral segment of the middle lobe (arrow).
CT image through the mid-chest shows the corresponding wedge-shaped opacity (arrowhead) and
thrombus in the pulmonary arteries (arrows).

CT: computed tomography.

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Chest radiograph and CT of the Westermark sign

Westermark sign in a patient with occlusive pulmonary embolism.

(A) Chest radiograph magnified A-P view shows a region of oligemia in the left lower lung (asterisk).

(B) Chest CT shows a large thrombus in the left main pulmonary artery (arrow).

A-P: anteroposterior; CT: computed tomography.

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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.

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§ 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.

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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

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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.

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Evaluation of the nonpregnant adult with low probability of pulmonary

embolism

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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.

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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.

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Modified Geneva score

Variables Points

Risk factors Age >65 years 1

Previous deep venous thrombosis or pulmonary embolism 3

Surgery under general anesthesia or fracture of the lower limbs 2

within one month

Active malignancy (solid or hematologic; currently active or cured 2

within the last year)

Symptoms Unilateral lower-limb pain 3

Hemoptysis 2

Signs Heart rate 75 to 94 beats per minute 3

≥95 beats per minute 5

Pain on lower limb deep venous palpation and unilateral edema 4

Total
points

Pre-test Low 0 to 3
probability
Intermediate 4 to 10
assessment
High ≥11

From Annals of Internal Medicine, Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency
department: the revised Geneva score. Ann Intern Med 2006; 144(3):165-71. Copyright © 2006 American College of Physicians. All
rights reserved. Reprinted with the permission of American College of Physicians, Inc.

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The pulmonary embolism rule out criteria (PERC rule)* [1]

Age <50 years

Heart rate <100 bpm

Oxyhemoglobin saturation ≥95%

No hemoptysis

No estrogen use

No prior DVT or PE

No unilateral leg swelling

No surgery/trauma requiring hospitalization within the prior four weeks

DVT: deep venous thrombosis; PE: pulmonary embolus; bpm: beats per minute.

* This rule is only valid in patients with a low clinical probability of PE (gestalt estimate <15 percent). In
patients with a low probability of PE who fullfil all eight criteria, the likelihood of PE is low and no further
testing is required. All other patients should be considered for further testing with sensitive D-dimer or
imaging.

Reference:

1. Kline JA, Courtney DM, Kabrhel C, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J
Thromb Haemost 2008; 6:772.

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Causes of high plasma D-dimer

Condition Mechanism

Thromboembolism: Intravascular thrombosis and fibrinolysis

Arterial
Myocardial infarction
Stroke
Acute limb ischemia
Intracardiac thrombus
Venous
Deep vein thrombosis
Pulmonary embolism
Disseminated intravascular coagulation (DIC)

Inflammation: Activation of the acute inflammatory response and

COVID-19 coagulation pathway, intravascular thrombosis and
Other severe infections fibrinolysis

Sepsis
DIC

Surgery/trauma Tissue ischemia, tissue necrosis

Liver disease Reduced clearance of fibrin degradation products

Kidney disease Multiple, including renal vein thrombosis and

nephrotic syndrome

Vascular disorders: Intravascular thrombosis and fibrinolysis

Vascular malformations
Sickle cell disease vaso-occlusion

Malignancy Multiple, including vascular abnormalities, cancer

procoagulant, and microvascular thrombosis

Thrombolytic therapy Fibrin breakdown

Pregnancy: Physiologic changes in the coagulation system

Normal pregnancy Microvascular thrombosis and fibrin deposition
Preeclampsia and eclampsia

Plasma D-dimer is a product of clot breakdown, released upon degradation of polymerized, crosslinked
fibrin (if non-crosslinked fibrinogen was degraded, D-monomers would be released). Elevated plasma D-
dimer levels indicate that coagulation has been activated, fibrin clot has formed, and clot degradation by
plasmin has occurred. There are many causes of elevated D-dimer; identification of the underlying cause
requires correlation with other findings, including the clinical picture and other laboratory results. Refer

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to UpToDate for further explanation of fibrinogen domain structure and pathophysiology of the
disorders listed here.

COVID-19: coronavirus disease 2019; DIC: disseminated intravascular coagulation.

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V/Q scan results and diagnosis of pulmonary embolism

Clinical probability of emboli

V/Q Scan Result
High Intermediate Low

High 96 88 56

Intermediate 66 28 16

Low 40 16 4

Normal or near normal 0 6 2

All numbers are percentages.

V/Q: ventilation/perfusion.

Data from: PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective
investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990; 263:2753.

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V/Q scan low probability of pulmonary embolism

Low probability V/Q scan. Anterior view perfusion image from a V/Q scan (A) shows a right lower lobe
defect (arrow). Chest CT pulmonary angiogram (B) shows bilateral lower lobe opacities (arrowheads)
suggestive of pneumonia and no thrombus in the pulmonary arteries (not shown).

V/Q scan: ventilation/perfusion scan; CT: computed tomography

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Catheter-based angiogram of a pulmonary embolus

Pulmonary embolus. Frontal image from a selective right pulmonary artery angiogram shows a filling
defect (arrow).

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V/Q scan and CT of small pulmonary emboli

Small pulmonary emboli. VQ scan left anterior oblique view perfusion image (A) shows a subsegmental
defect (arrowhead) reported as intermediate probability of pulmonary embolism. Chest CT pulmonary
angiogram (B) shows a thrombus in one of the left lower lobe pulmonary artery branches (arrow).

V/Q: ventilation/perfusion; CT: computed tomography.

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CT of multifocal pulmonary emboli

Multifocal pulmonary emboli. Chest CT angiogram images show filling defects in the pulmonary arteries
of to the lingula (A, arrow) and right lower lobe (B, arrow).

CT: computed tomography.

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Contributor Disclosures
B Taylor Thompson, MD No relevant financial relationship(s) with ineligible companies to
disclose. Christopher Kabrhel, MD, MPH Equity Ownership/Stock Options: Insera [Neurovascular
intervention]. Grant/Research/Clinical Trial Support: Diagnostica Stago [Venous thromboembolism];
Griffols [Venous thromboembolism]. Consultant/Advisory Boards: Abbott [Venous thromboembolism];
BMS [Venous thromboembolism]; Boston Scientific [Venous thromboembolism]. All of the relevant
financial relationships listed have been mitigated. Constantino Pena, MD Equity Ownership/Stock
Options: Cagent Medical [Cardiovascular disease]. Consultant/Advisory Boards: Biotronik [Cardiovascular
devices]; Philips Healthcare [Imaging]; Surmodics [Cardiovascular devices]. Speaker's Bureau: Cook
Medical [Pulmonary embolism]; Cordis [Pulmonary embolism]; Penumbra [Pulmonary embolism]; Terumo
[Pulmonary embolism]. All of the relevant financial relationships listed have been mitigated. Jess Mandel,
MD, MACP, ATSF, FRCP No relevant financial relationship(s) with ineligible companies to disclose. Korilyn S
Zachrison, MD, MSc No relevant financial relationship(s) with ineligible companies to disclose. Geraldine
Finlay, MD No relevant financial relationship(s) with ineligible companies to disclose.

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.

Conflict of interest policy

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