Review | doi: 10.1111/j.1365-2796.2010.02254.x
Contemporary management of pulmonary embolism: the
answers to ten questions
H. Bounameaux
From the Division of Angiology and Hemostasis, Department of Internal Medicine, University Hospitals of Geneva and Faculty of Medicine, Geneva,
Switzerland
Abstract. Bounameaux H (Division of Angiology and started to avoid potentially fatal recurrence. Treat-
Hemostasis, Department of Internal Medicine, Uni- ment starts for an initial 3-month period with a 5-day
versity Hospitals of Geneva and Faculty of Medicine, course of parenteral unfractionated or low-molecu-
Geneva, Switzerland). Contemporary management lar-weight heparin or fondaparinux overlapping with
of pulmonary embolism: the answers to ten ques- and followed by oral vitamin K antagonists monitored
tions (Review). J Intern Med 2010; 268: 218–231. to maintain an international normalized ratio of 2–3.
This initial period of 3 months may then be followed
Pulmonary embolism (PE) cannot be diagnosed solely by a long-term secondary prevention period in pa-
on a clinical basis, because of the lack of sensitivity tients who experience an idiopathic thromboembolic
and specificity of clinical signs and symptoms. Pul- event and are at low risk of bleeding. New oral antico-
monary angiography is invasive and resource agulants that do require patient monitoring and
demanding. Because the prevalence of PE is relatively might exhibit a more favourable benefit–risk balance
low (20% or less) amongst individuals who are clini- are currently under extensive clinical testing and
cally suspected of having the disease, submitting all might change the situation in the near future. A criti-
of them to imaging (multi-detector CT angiography or cal appraisal of the contemporary management of
ventilation ⁄ perfusion lung scintigraphy) would not suspected PE is given in this overview with the discus-
be cost-effective. Therefore, diagnostic algorithms sion of 10 practical questions.
have been developed that include clinical probability
assessment and D-dimer measurement to select the Keywords: anticoagulant therapy, clinical probability,
patients who require noninvasive imaging. Once the D-dimer, helical CT, pulmonary embolism, ultraso-
diagnosis is suspected or confirmed, therapy must be nography.
known as venous thromboembolism (VTE). Second,
Introduction
novel noninvasive diagnostic tools such as venous
Pulmonary embolism (PE), the source of which is compression ultrasonography (CUS), fibrin D-dimer
predominantly thrombosis of the deep veins (DVT) (DD) measurement and multi-detector computed
of the legs, is the third most common cause of tomography angiography (MDCTA) have become
mortality because of cardiovascular disease, after available. These techniques have drastically reduced
coronary artery disease and stroke. In addition, the need for invasive tools such as phlebography and
late sequelae of DVT may produce disabling leg pulmonary angiography. Third, the index of suspi-
symptoms in a substantial proportion of patients, cion has progressively increased and resulted in at
including venous ulcers in a minority, resulting in least 80% of patients with suspected VTE being
a considerable economic burden. Furthermore, referred to a diagnostic centre but found not to have
chronic thromboembolic pulmonary hypertension the disease. Fourth, efficient mainly noninvasive
may develop as a late complication of PE in a strategies have been validated in large-scale outcome
small subset of patients. studies, and their costs have become an issue [1]. In
parallel, the therapeutic management has also been
During the past two decades, the approach to diag- modified; risk stratification has been recommended
nosing DVT and PE has changed considerably. First, and new drugs as well as new regimens of old drugs
it has been accepted that these two conditions are have emerged that might change our practice in the
different manifestations of a single entity that was near future.
218 ª 2010 Blackwell Publishing Ltd
, H. Bounameaux
| Review: Contemporary management of pulmonary embolism
The aim of the present overview is to discuss these Rodger et al. [8] showed that interobserver reliability
diagnostic and therapeutic changes by answering 10 was higher when using an explicit clinical model
questions regarding nonmassive PE, which repre- (kappa coefficient of agreement = 0.62 vs. 0.33 for
sents the vast majority (about 95%) of all PE events. implicit evaluation). In addition, explicit clinical mod-
els or scores are useful educational tools. All these
means of assessing clinical likelihood of PE allow a
How should we manage a patient with clinically suspected PE?
fairly accurate classification of patients into three
Once the possibility of PE has been raised, the ini- categories corresponding to a prevalence of the dis-
tial step of any diagnostic work-up consists of ease of 5–10% (low clinical probability), 20–30%
assessing the clinical probability of the patient (intermediate clinical probability) and 60–80% (high
having the disease. The aim of this step is to (i) clinical probability). Most patients with suspected PE
identify the patients (probably those with a high have a low or intermediate clinical probability of hav-
and intermediate clinical probability) who require ing the disease. Those with a low or intermediate
anticoagulant treatment whilst awaiting the results probability of PE can usually be investigated by en-
of diagnostic tests and (ii) select the patients (those tirely noninvasive algorithms. However, these rules
with a nonhigh clinical probability) in whom the also have limitations. Computation of the original
diagnosis of PE can be excluded based on a nega- Geneva score [4] requires arterial blood gas values
tive DD test result (Fig. 1). whilst breathing room air, a variable that was not
available in 15% of the patients in the external valida-
Pulmonary embolism cannot be diagnosed on a clini- tion sample [5]. The Canadian score (Table 1) in-
cal basis alone, because of the lack of sensitivity and cludes the clinician’s judgment of whether an alter-
specificity of isolated clinical signs and symptoms [2]. native diagnosis is more likely than that of PE [3].
Indeed, clinical symptoms, signs and abnormalities This criterion has major weight in this score and can
of blood gases, chest radiograph and electrocardio- clearly not be standardized, thereby hampering its
gram have a low predictive value for suspected PE use by nonclinical health professionals.
when considered individually. Nevertheless, clini-
cians can combine these findings effectively either To obviate the logistical and standardization prob-
implicitly (or empirically) or by prediction rules (or lems of the two aforementioned scores, the Geneva
scores) to classify patients according to their proba- group derived a new prediction rule from a large mul-
bility of having the disease; this is usually referred to ticentre cohort of patients admitted to the emergency
as ‘clinical probability’. ward for clinically suspected PE [9]. The rule is
entirely based on readily available clinical variables
Two scores have been proposed [3, 4] and externally and is independent of physicians’ implicit judgment
validated [5] that are as, but not more, accurate than (Table 1). In an external validation set of the new score,
implicit judgment [6, 7]. Nevertheless, in a study of the prevalence of PE was 8% in the low-probability
110 patients who received duplicate assessments, category (0–3 points), 28% in the intermediate group
(4–10 points) and 74% in the high-probability group
(11 points or more) [9]. Although the clinical data in
the validation sample were collected prospectively,
this new score, the so-called revised Geneva score,
was calculated retrospectively. To be considered fully
validated, it needed be used prospectively in a formal
outcome study with patient follow-up. This has
been realized in two independent cohorts. First, Klok
et al. [10] reported the same predictive accuracy in a
series of 300 consecutive patients as in the deri-
vation and initial retrospective validation samples.
Moreover, the diagnostic accuracy was similar to
that of the Wells’ score, which was also assessed in
this series. A second prospective validation of this
Fig. 1 Multi-detector computed tomography angiography in score was obtained in a cohort of 1819 patients with
a 32-year-old pregnant woman showing multiple bilateral suspected PE [11], which again showed that the
pulmonary emboli, including (arrows) in the right pulmonary accuracy was similar to that obtained with the Wells’
artery and in the left inferior lobar artery. rule.
ª 2010 Blackwell Publishing Ltd Journal of Internal Medicine 268; 218–231 219
Contemporary management of pulmonary embolism: the
answers to ten questions
H. Bounameaux
From the Division of Angiology and Hemostasis, Department of Internal Medicine, University Hospitals of Geneva and Faculty of Medicine, Geneva,
Switzerland
Abstract. Bounameaux H (Division of Angiology and started to avoid potentially fatal recurrence. Treat-
Hemostasis, Department of Internal Medicine, Uni- ment starts for an initial 3-month period with a 5-day
versity Hospitals of Geneva and Faculty of Medicine, course of parenteral unfractionated or low-molecu-
Geneva, Switzerland). Contemporary management lar-weight heparin or fondaparinux overlapping with
of pulmonary embolism: the answers to ten ques- and followed by oral vitamin K antagonists monitored
tions (Review). J Intern Med 2010; 268: 218–231. to maintain an international normalized ratio of 2–3.
This initial period of 3 months may then be followed
Pulmonary embolism (PE) cannot be diagnosed solely by a long-term secondary prevention period in pa-
on a clinical basis, because of the lack of sensitivity tients who experience an idiopathic thromboembolic
and specificity of clinical signs and symptoms. Pul- event and are at low risk of bleeding. New oral antico-
monary angiography is invasive and resource agulants that do require patient monitoring and
demanding. Because the prevalence of PE is relatively might exhibit a more favourable benefit–risk balance
low (20% or less) amongst individuals who are clini- are currently under extensive clinical testing and
cally suspected of having the disease, submitting all might change the situation in the near future. A criti-
of them to imaging (multi-detector CT angiography or cal appraisal of the contemporary management of
ventilation ⁄ perfusion lung scintigraphy) would not suspected PE is given in this overview with the discus-
be cost-effective. Therefore, diagnostic algorithms sion of 10 practical questions.
have been developed that include clinical probability
assessment and D-dimer measurement to select the Keywords: anticoagulant therapy, clinical probability,
patients who require noninvasive imaging. Once the D-dimer, helical CT, pulmonary embolism, ultraso-
diagnosis is suspected or confirmed, therapy must be nography.
known as venous thromboembolism (VTE). Second,
Introduction
novel noninvasive diagnostic tools such as venous
Pulmonary embolism (PE), the source of which is compression ultrasonography (CUS), fibrin D-dimer
predominantly thrombosis of the deep veins (DVT) (DD) measurement and multi-detector computed
of the legs, is the third most common cause of tomography angiography (MDCTA) have become
mortality because of cardiovascular disease, after available. These techniques have drastically reduced
coronary artery disease and stroke. In addition, the need for invasive tools such as phlebography and
late sequelae of DVT may produce disabling leg pulmonary angiography. Third, the index of suspi-
symptoms in a substantial proportion of patients, cion has progressively increased and resulted in at
including venous ulcers in a minority, resulting in least 80% of patients with suspected VTE being
a considerable economic burden. Furthermore, referred to a diagnostic centre but found not to have
chronic thromboembolic pulmonary hypertension the disease. Fourth, efficient mainly noninvasive
may develop as a late complication of PE in a strategies have been validated in large-scale outcome
small subset of patients. studies, and their costs have become an issue [1]. In
parallel, the therapeutic management has also been
During the past two decades, the approach to diag- modified; risk stratification has been recommended
nosing DVT and PE has changed considerably. First, and new drugs as well as new regimens of old drugs
it has been accepted that these two conditions are have emerged that might change our practice in the
different manifestations of a single entity that was near future.
218 ª 2010 Blackwell Publishing Ltd
, H. Bounameaux
| Review: Contemporary management of pulmonary embolism
The aim of the present overview is to discuss these Rodger et al. [8] showed that interobserver reliability
diagnostic and therapeutic changes by answering 10 was higher when using an explicit clinical model
questions regarding nonmassive PE, which repre- (kappa coefficient of agreement = 0.62 vs. 0.33 for
sents the vast majority (about 95%) of all PE events. implicit evaluation). In addition, explicit clinical mod-
els or scores are useful educational tools. All these
means of assessing clinical likelihood of PE allow a
How should we manage a patient with clinically suspected PE?
fairly accurate classification of patients into three
Once the possibility of PE has been raised, the ini- categories corresponding to a prevalence of the dis-
tial step of any diagnostic work-up consists of ease of 5–10% (low clinical probability), 20–30%
assessing the clinical probability of the patient (intermediate clinical probability) and 60–80% (high
having the disease. The aim of this step is to (i) clinical probability). Most patients with suspected PE
identify the patients (probably those with a high have a low or intermediate clinical probability of hav-
and intermediate clinical probability) who require ing the disease. Those with a low or intermediate
anticoagulant treatment whilst awaiting the results probability of PE can usually be investigated by en-
of diagnostic tests and (ii) select the patients (those tirely noninvasive algorithms. However, these rules
with a nonhigh clinical probability) in whom the also have limitations. Computation of the original
diagnosis of PE can be excluded based on a nega- Geneva score [4] requires arterial blood gas values
tive DD test result (Fig. 1). whilst breathing room air, a variable that was not
available in 15% of the patients in the external valida-
Pulmonary embolism cannot be diagnosed on a clini- tion sample [5]. The Canadian score (Table 1) in-
cal basis alone, because of the lack of sensitivity and cludes the clinician’s judgment of whether an alter-
specificity of isolated clinical signs and symptoms [2]. native diagnosis is more likely than that of PE [3].
Indeed, clinical symptoms, signs and abnormalities This criterion has major weight in this score and can
of blood gases, chest radiograph and electrocardio- clearly not be standardized, thereby hampering its
gram have a low predictive value for suspected PE use by nonclinical health professionals.
when considered individually. Nevertheless, clini-
cians can combine these findings effectively either To obviate the logistical and standardization prob-
implicitly (or empirically) or by prediction rules (or lems of the two aforementioned scores, the Geneva
scores) to classify patients according to their proba- group derived a new prediction rule from a large mul-
bility of having the disease; this is usually referred to ticentre cohort of patients admitted to the emergency
as ‘clinical probability’. ward for clinically suspected PE [9]. The rule is
entirely based on readily available clinical variables
Two scores have been proposed [3, 4] and externally and is independent of physicians’ implicit judgment
validated [5] that are as, but not more, accurate than (Table 1). In an external validation set of the new score,
implicit judgment [6, 7]. Nevertheless, in a study of the prevalence of PE was 8% in the low-probability
110 patients who received duplicate assessments, category (0–3 points), 28% in the intermediate group
(4–10 points) and 74% in the high-probability group
(11 points or more) [9]. Although the clinical data in
the validation sample were collected prospectively,
this new score, the so-called revised Geneva score,
was calculated retrospectively. To be considered fully
validated, it needed be used prospectively in a formal
outcome study with patient follow-up. This has
been realized in two independent cohorts. First, Klok
et al. [10] reported the same predictive accuracy in a
series of 300 consecutive patients as in the deri-
vation and initial retrospective validation samples.
Moreover, the diagnostic accuracy was similar to
that of the Wells’ score, which was also assessed in
this series. A second prospective validation of this
Fig. 1 Multi-detector computed tomography angiography in score was obtained in a cohort of 1819 patients with
a 32-year-old pregnant woman showing multiple bilateral suspected PE [11], which again showed that the
pulmonary emboli, including (arrows) in the right pulmonary accuracy was similar to that obtained with the Wells’
artery and in the left inferior lobar artery. rule.
ª 2010 Blackwell Publishing Ltd Journal of Internal Medicine 268; 218–231 219
