Treatment, Prognosis, and Follow Up of Acute Pulmonary Embolism

Treatment, prognosis, and follow-up of acute pulmonary embolism in ad... https://www.uptodate.com/contents/treatment-prognosis-and-follow-up-...
Treatment, prognosis, and follow-up of acute

pulmonary embolism in adults
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��: Aaron S Weinberg, MD, MPhil, Parth Rali, MD

�� : Jess Mandel, MD, MACP, ATSF, FRCP, Korilyn S Zachrison, MD, MSc
�� : Geraldine Finlay, MD
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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2023.

This topic last updated: Sep 06, 2023.
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INTRODUCTION
Acute pulmonary embolism (PE) is a common and sometimes fatal disease with a variable
clinical presentation. It is critical that therapy be administered in a timely fashion [1-5].
The treatment, prognosis, and follow-up of patients with acute PE are reviewed here. The
epidemiology, pathophysiology, clinical presentation, and diagnosis of PE, as well as
detailed discussions of anticoagulation and thrombolysis in patients with PE are presented
separately. (See "Overview of acute pulmonary embolism in adults" and "Clinical
presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute
pulmonary embolism" and "Approach to thrombolytic (fibrinolytic) therapy in acute
pulmonary embolism: Patient selection and administration" and "Venous
thromboembolism: Initiation of anticoagulation".)
The approach to treatment outlined in this topic is, in general, consistent with strategies
outlined by several international societies including the American College of Chest
Physicians, the American College of Physicians, the European Society of Cardiology, the
European Respiratory Society, the American Society of hematology, and others [6-10].
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INITIAL APPROACH AND RESUSCITATION
The initial approach to patients with suspected PE should focus upon stabilizing the patient
while clinical evaluation and definitive diagnostic testing are ongoing [11]. Anticoagulation
should be initiated even prior to confirming the diagnosis of PE if risk benefit regarding
suspicion of PE and risk of bleeding appear favorable. Once diagnosis is confirmed, risk
stratification is crucial. It is also important to triage and risk stratify the patients to identify
which patients may benefit from inter hospital transfer.
Assess hemodynamic stability — The initial approach to patients with suspected PE

depends upon whether the patient is hemodynamically stable or unstable as shown in the
algorithm ( algorithm 1A-B). (See "Overview of acute pulmonary embolism in adults",
section on 'Nomenclature'.)
● Hemodynamically unstable PE (ie, high-risk or "massive" PE) is that which presents

with hypotension; hypotension is defined as a systolic blood pressure (BP) <90 mmHg
for a period >15 minutes or a drop in systolic blood pressure substantially below
baseline (generally a drop of >40 mmHg, hypotension requiring vasopressors, or clear
evidence of shock). Importantly, these high-risk patients are a heterogeneous group
[8] with the extremely unstable patients suffering cardiac arrest.
● Hemodynamically stable PE is defined as PE that does not meet the definition of

hemodynamically unstable PE. These patients are also a very heterogeneous group
ranging from patients with small PE, stable BP, normal right ventricular size and
function and normal biomarkers, with a normal simplified Pulmonary Embolism
Severity Index (sPESI) ("low risk") to those patients with extensive emboli with
tachycardia, right ventricular dysfunction, abnormal biomarkers, and borderline BP
(ie, intermediate risk "submassive" PE). Based upon the European Society of
Cardiology (ESC) guidelines [8], these patients have been categorized as
"intermediate-low risk" (abnormal right ventricular function or elevated serum
troponin) and intermediate-high risk (abnormal right ventricular function and
elevated serum troponin).
Importantly, patients may become hemodynamically stable following resuscitation, or

become unstable during the evaluation and early treatment period, both of which
necessitate rapid redirection of therapeutic strategies. It is important to point out that
proximal deep venous thrombosis (DVT) is associated with adverse PE-related outcomes.
Even though not part of current classification system, it is a very important tool in risk
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stratification [12,13].
Hemodynamically stable — The majority of patients with PE are hemodynamically stable

upon presentation [14,15]. The initial approach should focus upon general supportive
measures while the diagnostic evaluation is ongoing; supportive measures include the
following (see "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult
with suspected acute pulmonary embolism" and 'Hemodynamically stable patients' below):
● Peripheral intravenous access with or without intravenous fluids (see 'Hemodynamic

support' below)
● Oxygen supplementation (see 'Respiratory support' below)
● Empiric anticoagulation depending upon the clinical suspicion for PE, risk of bleeding,
and expected timing of definitive diagnostic tests (see 'Empiric anticoagulation' below)
Hemodynamically unstable — A small percentage of patients with PE present with

hemodynamic instability or shock (<10 percent, ie, high-risk or "massive" PE). When
patients with suspected PE present with hypotension, initial support should focus upon
restoring perfusion and vasopressor support, as well as oxygenation and, if necessary,
stabilizing the airway with intubation and mechanical ventilation [11]. (See 'Hemodynamic
support' below and 'Respiratory support' below and "Overview of acute pulmonary
embolism in adults", section on 'Nomenclature'.)
● For most patients who become hemodynamically stable following resuscitation and in
whom the clinical suspicion for PE is high, we prefer immediate anticoagulation with
unfractionated heparin and prompt imaging for definitive diagnosis (usually
computed tomographic pulmonary angiography [CTPA]). For patients with a moderate
or low suspicion for PE, the use of empiric anticoagulation depends upon the timing
of diagnostic testing. Diagnostic testing in patients with suspected PE is presented
elsewhere. (See 'Empiric anticoagulation' below and "Clinical presentation, evaluation,
and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism",
section on 'Hemodynamically stable patients'.)
● For patients with a high clinical suspicion for PE who are hemodynamically unstable
(ie, systolic blood pressure <90 mmHg for >15 minutes, hypotension requiring
vasopressors, or clear evidence of shock), and in whom transfer to radiology for a
CTPA is considered unsafe, a portable perfusion scan can be done at some centers.
When portable perfusion scanning or CTPA is not available or is unsafe, we prefer
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bedside echocardiography (transthoracic or transesophageal) to obtain a presumptive

diagnosis of PE (right ventricle enlargement/hypokinesis, regional wall motion
abnormalities that spare the right ventricular apex [McConnell's sign], or visualization
of clot) prior to the empiric administration of systemic thrombolytic therapy (ie,
reperfusion therapy). If bedside echocardiography is delayed or unavailable, the use
of thrombolytic therapy as a life-saving measure should be individualized; if not used,
the patient should receive empiric anticoagulation. The initiation of anticoagulation
should not be delayed while considering other, more aggressive interventional
therapies. We suggest a similar approach for select patients with known PE whose
course becomes complicated by hypotension during anticoagulation in whom the
suspicion for recurrent PE despite anticoagulation is high. Some clinicians use bedside
ultrasonography to demonstrate evidence of DVT, which may raise the suspicion for
PE in the absence of another reasonable diagnosis and facilitate decision-making. (See
'Hemodynamically unstable patients' below.)
For patients with suspected PE who remain hemodynamically unstable and the clinical
suspicion is low or moderate, the approach to empiric anticoagulation should be the
same as for patients who are hemodynamically stable; empiric thrombolysis is not
justified in this population.
The echocardiographic findings suggestive of PE and the diagnostic approach to

hemodynamically unstable patients, as well as the indications for thrombolytic therapy and
its alternative, embolectomy, are discussed separately. (See "Clinical presentation,
evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary
embolism", section on 'Echocardiography' and "Clinical presentation, evaluation, and
diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on
'Hemodynamically unstable patients' and 'Embolectomy' below and "Approach to
thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and
administration", section on 'Hemodynamically unstable patients (high-risk pulmonary
embolism)'.)
Pulmonary embolism response teams (PERT) — The decision to administer

thrombolysis is strongly influenced by additional clinical factors. For example, while a
patient with proven PE-induced shock who is unconscious requiring very high doses of
vasopressors is a candidate for immediate intravenous thrombolytic therapy, a patient who
has low blood pressure for 20 minutes but who is awake, alert, and comfortable, with low
oxygenation requirement might be considered for anticoagulation alone, or a catheter-
based interventional procedure. Thus, when feasible, it is prudent to adopt a
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multidisciplinary approach to facilitate management of hemodynamically unstable patients

with PE as well as selected patients with intermediate-high risk PE; some centers have
incorporated a "pulmonary embolism response team" (PERT) to facilitate the process
[15-18].
There are limited data that describe the impact of PERT. One single center retrospective
study examined outcomes in patients with PE before and after the implementation of PERT
[19]. PERT was associated with a reduction in 30 day inpatient mortality (4.7 versus 8.5
percent), lower rates of major bleeding (8.3 versus 17 percent), shorter time to therapeutic
anticoagulation (12.6 versus 16.3 hours), and decreased use of inferior vena cava filters
(22.2 versus 16.4 percent) [19]. The mortality benefit was most pronounced in the subgroup
of patients with intermediate- and high-risk PE (5.3 versus 10 percent), suggesting that this
population derive the greatest benefit from PERT. There was also an increased use of
thrombolytic and catheter-based strategies that did not reach statistical significance. In
contrast, in another single-center study of 2042 patients, among which 165 were evaluated
by PERT, there was no difference in the mortality between the pre-PERT and post-PERT
implementation phases [20] and a meta-analysis of 22 studies reported that PERT lead to
greater use of advanced therapies and shorter in-hospital stay but no survival benefit [21].
The 2019 European Society of Cardiology (ESC) guidelines have included a discussion of the
utility of PERT and given it a class IIa level C recommendation [8].
Initial therapies
Respiratory support — Supplemental oxygen should be administered to target an

oxygen saturation ≥90 percent. Severe hypoxemia, hemodynamic collapse, or respiratory
failure should prompt consideration of intubation and mechanical ventilation. Importantly,
patients with coexistent right ventricle failure are prone to hypotension following
intubation. Thus, in this population, it may be prudent to consult an expert in
cardiovascular anesthesia and high plateau pressures should be avoided. The principles of
intubation, mechanical ventilation, and extracorporeal membrane oxygenation (which has
been used successfully in severely ill patients with refractory hypoxemia and/or
hypotension), are discussed separately. (See "Induction agents for rapid sequence
intubation in adults for emergency medicine and critical care" and "Direct laryngoscopy and
endotracheal intubation in adults" and "Extracorporeal life support in adults in the
intensive care unit: Overview" and "Overview of initiating invasive mechanical ventilation in
adults in the intensive care unit", section on 'Indications'.)
Hemodynamic support — The precise threshold that warrants hemodynamic support
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depends upon the patient's baseline blood pressure and whether there is clinical evidence
of hypoperfusion (eg, change in mental status, diminished urine output). In general, we
prefer small volumes of intravenous fluid (IVF), usually 250 to 500 mL of normal saline,
followed by vasopressor therapy should perfusion fail to respond to IVF.
● Intravenous fluid – IVF is first-line therapy for patients with hypotension. However, in
patients with right ventricular (RV) dysfunction, limited data suggest that aggressive
fluid resuscitation is not beneficial, and may be harmful [22-26]. The rationale for
limiting IVF administration comes from preclinical studies and one small observational
study in humans, which reported that small volumes of IVF increase the cardiac index
in patients with PE, while excessive amounts of IVF result in RV overstretch (ie, RV
overload), RV ischemia, and worsening RV failure. The patient's volume status should
be carefully assessed as this could influence the approach to fluid administration.
● Vasopressors – Intravenous vasopressors are administered when adequate perfusion

is not restored with IVF. The optimal vasopressor for patients with shock due to acute
PE is unknown, but norepinephrine is generally preferred ( table 1) [23,27-29].
Options include:
• Norepinephrine – Norepinephrine is the most frequently utilized agent in this

population because it is effective and less likely to cause tachycardia [23]. Other
alternatives include dopamine and epinephrine, but tachycardia, which can
exacerbate hypotension, can occur with these agents [27].
• Dobutamine – Dobutamine is sometimes used to increase myocardial contractility

in patients with circulatory shock from PE. However, it also results in systemic
vasodilation which worsens hypotension, particularly at low doses [28,29]. To
mitigate this effect, we typically initially add norepinephrine to dobutamine; as the
dose of dobutamine is increased, the effects of dobutamine-induced myocardial
contractility exceed those of vasodilation, potentially allowing norepinephrine to
be weaned off.
Isoproterenol, amrinone, and milrinone have been investigated in animal models, but
have not proven useful for hypotension due to acute PE [30,31]. Physiologic properties
and use of vasopressors are discussed separately. (See "Use of vasopressors and
inotropes".)
Empiric anticoagulation — The administration of empiric anticoagulation depends upon

the risk of bleeding, clinical suspicion for PE (calculator 1) ( table 2) and the expected
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timing of diagnostic tests [5,26]. There is no optimal prediction tool for assessing bleeding
risk in patients with PE. Similarly, while many experts propose use of the Wells score to
assess the risk of PE, careful clinical judgment is acceptable and many experts use gestalt
estimates, the details of which are discussed separately. (See "Clinical presentation,
embolism", section on 'Determining the pretest probability of pulmonary embolism' and
"Selecting adult patients with lower extremity deep venous thrombosis and pulmonary
embolism for indefinite anticoagulation", section on 'Assessing the risk of bleeding'.)
One strategy is shown below:
● Low risk for bleeding – Patients without risk factors for bleeding ( table 3) have a
three-month bleeding risk of <2 percent; in such patients, empiric anticoagulation
may be considered in the following patient groups:
• A high clinical suspicion for PE (eg, Wells score >6)

• A moderate clinical suspicion for PE (eg, Wells score 2 to 6), in whom the diagnostic
evaluation is expected to take longer than four hours
• A low clinical suspicion for PE (eg, Wells score <2), if the diagnostic evaluation is
expected to take longer than 24 hours
● Unacceptably high risk for bleeding – For patients with absolute contraindications to
anticoagulant therapy (eg, recent surgery, hemorrhagic stroke, active bleeding) or
those assessed by their clinician to be at an unacceptably high risk of bleeding (eg,
aortic dissection, intracranial or spinal cord tumors), empiric anticoagulation should
not be administered. The diagnostic evaluation should be expedited so that alternate
therapies (eg, inferior vena cava filter, embolectomy) can be initiated if PE is
confirmed.
● Moderate risk for bleeding – Patients with one or more risk factors for bleeding
( table 3) have a moderate (>3 percent) to high (>13 percent) risk of bleeding. In
such patients, empiric anticoagulant therapy may be administered on a case-by-case
basis according to the assessed risk-benefit ratio and the values and preferences of
the patient. Additionally, use of these bleeding estimates should not preclude clinical
judgment when making a decision to anticoagulate in this population. As an example,
we might empirically anticoagulate a patient with moderate risk of bleeding if they
have a high clinical suspicion for PE, severe respiratory compromise, or an expected
delay for the insertion of a vena caval filter.
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Typically, menstruation, epistaxis, and the presence of minor hemoptysis are not
contraindications to anticoagulation but should be monitored during anticoagulant
therapy. (See 'Monitoring and follow-up' below.)
It is common that patients with PE may have hemoptysis largely due to pulmonary
infarction, and anticoagulation should not be stopped or considered contraindicated for
that reason. The optimal agent for empiric anticoagulation depends upon the presence or
absence of hemodynamic instability, the anticipated need for procedures or thrombolysis,
and the presence of risk factors and comorbidities ( table 4). As an example, low
molecular weight (LMW) heparin may be chosen for patients with hemodynamically stable
PE who do not have renal insufficiency in whom rapid onset of anticoagulation needs to be
guaranteed (ie, therapeutic levels are achieved with four hours). While unfractionated
heparin may be preferred by most experts in patients who are hemodynamically unstable
in anticipation of a potential need for thrombolysis or embolectomy, some trials with
catheter-based treatments (lysis and embolectomy) allowed patients on background LMW
heparin [32,33]. Direct thrombin and factor Xa inhibitors should not be used in
hemodynamically unstable patients. (See "Venous thromboembolism: Initiation of
anticoagulation".)
DEFINITIVE THERAPY
Our approach — For patients in whom the diagnostic evaluation excludes PE (see "Clinical
presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute
pulmonary embolism"), anticoagulant therapy should be discontinued if it was initiated
empirically, and alternative causes of the patient's symptoms and signs should be sought
( algorithm 1A-B).
For patients in whom the diagnostic evaluation confirms PE, we suggest an approach that
is stratified according to whether the patient is hemodynamically stable or unstable
( algorithm 1A-B). At any time, the strategy may need to be redirected as complications of
PE or therapy arise. (See 'Hemodynamically stable patients' below and 'Hemodynamically
unstable patients' below.)
Hemodynamically stable patients — Patients in this group are heterogeneous and have a
wide range of presentations as well as variable risk of recurrence and decompensation; it
includes those with low-risk, intermediate-low risk, and intermediate-high risk PE.
We suggest the following approach for most hemodynamically stable (ie, normotensive)
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patients with low-risk and intermediate-low risk PE ( algorithm 1A-B):
● For those in whom the risk of bleeding is low, anticoagulant therapy is indicated. (See
'Anticoagulation' below.)
● For those who have contraindications to anticoagulation or have an unacceptably

high bleeding risk, placement of an inferior vena cava (IVC) filter should be
performed. (See 'Inferior vena cava filters' below and "Placement of vena cava filters
and their complications".)
● For those in whom the risk of bleeding is moderate or high, therapy should be
individualized according to the assessed risk-benefit ratio and values and preferences
of the patient. As an example, a patient >75 years who is at risk of falling is not an
ideal candidate for anticoagulation; anticoagulation may be considered if a vena cava
filter cannot be placed (eg, inability to access the IVC due to extensive thrombus or
tumor). (See 'Empiric anticoagulation' above.)
It should be noted that when PE is proven and anticoagulation is contraindicated, an

IVC filter is still indicated, whether the PE is small or extensive and even in the
absence of residual deep venous thrombosis (DVT).
● For most hemodynamically stable patients, we recommend against thrombolytic

therapy (eg, low risk patients).
Hemodynamically stable (ie, normotensive) patients with intermediate-risk/submassive PE

who are anticoagulated, should be monitored closely for deterioration. Thrombolysis
and/or catheter-based therapies may be considered on a case-by-case basis when the
benefits are assessed by the clinician to outweigh the risk of hemorrhage. Examples of
such patients include those who have a large clot burden, severe RV
enlargement/dysfunction, high oxygen requirement, and/or are severely tachycardic
( table 5). The details of such therapies are discussed separately. (See "Approach to
administration", section on 'Systemic infusion (full-dose thrombolytic)'.)
Anticoagulation
Indications and duration — Anticoagulant therapy is indicated for patients with PE

in whom the risk of bleeding is low:
● Initial anticoagulation – Initial anticoagulant therapy is administered as soon as
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possible to quickly achieve therapeutic anticoagulation. A detailed discussion of agent

selection and patient selection for outpatient anticoagulation is presented separately.
(See "Venous thromboembolism: Initiation of anticoagulation" and 'Outpatient
anticoagulation' below.)
● Long-term anticoagulation (after discharge) – All patients are anticoagulated for a

minimum of three months. Agent selection and duration of long-term anticoagulation
in patients with PE and DVT are discussed in detail separately. (See "Venous
thromboembolism: Anticoagulation after initial management".)
● Indefinite anticoagulation – Select patients with PE are candidates for indefinite

anticoagulation. Patient selection depends upon the nature of the event (ie, provoked
or unprovoked), the presence of risk factors (eg, transient or persistent), the
estimated risk of bleeding and recurrence, as well as patient preferences and values
(eg, occupation, life expectancy, burden of therapy), and trials that support a benefit.
The rationale and indications for indefinite anticoagulation are described separately.
(See "Selecting adult patients with lower extremity deep venous thrombosis and
pulmonary embolism for indefinite anticoagulation".)
Outpatient anticoagulation — In select patients with PE, outpatient therapy can be

administered by giving the first dose of anticoagulant in the hospital or urgent care center,
with the remaining doses given at home. The decision to treat as an outpatient should be
made in the context of the patient's clinical condition, understanding of the risk-benefit
ratio, and their preferences. Although the ideal candidate is poorly defined, guideline
groups, several randomized trials, and meta-analyses suggest that, in patients with PE,
outpatient anticoagulation is safe and effective in carefully selected patients with all of the
following features [5,34-45]:
● Low risk of death – defined as Pulmonary Embolism Severity Index (PESI) class I or II
( table 6), or simplified PESI (sPESI) score = 0 (see 'Prognostic models' below)
● No requirement for supplemental oxygen
● No requirement for narcotics for pain control
● No respiratory distress
● Normal pulse and blood pressure
● No recent history of bleeding or risk factors for bleeding ( table 3)
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● No serious comorbid conditions (eg, ischemic heart disease, chronic lung disease,
liver or renal failure, thrombocytopenia, or cancer)
● Normal mental status with good understanding of risk and benefits, are not needle
averse (if low molecular weight [LMW] heparin chosen), and have good home support
(eg, do not live alone, have access to a telephone and clinician, can return to the
hospital quickly if there is clinical deterioration)
● Absence of concomitant DVT (a high clot burden in the lower extremities may increase
the risk of recurrence, death, or warrant additional therapy)
Support for outpatient therapy or early discharge following a brief inpatient stay is derived
from randomized studies and meta-analyses with flawed methodology [9,38,40,42]. As
examples:
● One open label, multicenter trial randomly assigned 344 patients with symptomatic
PE and a low risk of death (PESI I/II; ( table 6)) to receive either inpatient
(intravenous heparin followed by warfarin) or outpatient (subcutaneous LMW heparin
followed by warfarin) therapy [38]. Compared with inpatients, patients treated as an
outpatient had a slightly higher rate of recurrent venous thromboembolism (VTE; 0.6
percent versus 0 percent) and major bleeding events (1.8 percent versus 0 percent) at
90 days that was not statistically significant. Mortality was no different between the
groups (0.6 percent). The mean length of stay was 0.5 days for outpatients and 3.9
days for inpatients.
● A 2013 meta-analysis of 21 studies compared patients at low risk of death who were
anticoagulated for PE as an outpatient (discharged within 24 hours) with patients who
were treated as an inpatient and discharged after 72 hours (randomized and
observational studies were included) [40]. Compared with inpatient anticoagulation,
outpatient anticoagulation was not associated with a statistically significant difference
in the rate of recurrent VTE (1.7 versus 1.2 percent) and mortality (1.9 versus 0.74
percent), or major bleeding events (0.97 versus 1 percent); However, although
absolute rates of recurrent VTE and death were higher with outpatient treatment,
there was significant population and therapeutic regimen heterogeneity among the
included studies, limiting the interpretation of the results. A 2018 analysis of two
randomized trials reported low quality evidence that there was no difference in 30- or
90-day mortality, major bleeding, or recurrence between low risk patients with acute
PE who were treated as an inpatient or outpatient [46]. In a 2021 meta-analysis of 14
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studies of patients with low-risk PE, there was no difference in the mortality or
recurrence rate or rate of major bleeding among patients treated as an outpatient or
inpatient [42].
● A retrospective analysis of 1127 patients reported that the 14 day rate of adverse
events (recurrent VTE, major bleeding, or death) was 3 percent for outpatients
compared with 13 percent for inpatients and the three-month rate was 7 and 22
percent, respectively [47].
● In another randomized trial of 114 patients with PE who were discharged on

rivaroxaban and were at low risk of death the LOS was significantly reduced in early
discharge patients compared with those who were admitted (34 versus 5 hours) [48].
At three months, there were no bleeding events, recurrent VTE, or deaths.
● In a prospective analysis of 525 patients with PE who were discharged early and
treated with rivaroxaban, only three patients (0.6 percent) developed symptomatic
non-fatal VTE recurrence at three months follow-up and bleeding rates were low (1.2
percent) [49].
The ideal agent is unknown. Agent selection for outpatient anticoagulant therapy in
patients with PE is similar to that for DVT. (See "Overview of the treatment of proximal and
distal lower extremity deep vein thrombosis (DVT)", section on 'Outpatient versus inpatient
therapy'.)
Despite the fact that outpatient anticoagulation has been shown to be safe, this practice
may be uncommon. One retrospective review of 746 patients with PE who were potentially
eligible for anticoagulation at home, reported that only 1.7 percent were treated at home
and only 16 percent were discharged within two days [50]. However, clinician education
may change this practice. As an example, in one trial of 1763 patients diagnosed with PE in
the ED, an electronic intervention built into the electronic health record increased the
number of patients who could be discharged to home (17 percent versus 28 percent)
without increasing the risk of return visits to the ED, recurrent VTE, or mortality [51].
Patients with subsegmental PE — The increasing use of computed tomography (CT)

has led to the increased diagnosis of incidental (asymptomatic) PE and small subsegmental
PE (SSPE) ( figure 1).
One observational study reported that 15 percent of patients with symptomatic PE have
SSPE [52]. The true proportion of patients with asymptomatic SSPE is unknown [53].
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Although the clinical relevance of SSPE is unknown, a single subsegmental defect probably
does not have the same clinical outcome as a single segmental or lobar PE or multiple
SSPE. A retrospective review of 222 patients with PE, 36 percent of whom had SSPE,
reported that 87 percent were systemically anticoagulated while the remaining were not
anticoagulated due to bleeding or poor prognosis at the time of diagnosis [54]. Adverse
events were similar between SSPE patients and patients with more proximal emboli. (See
"Overview of acute pulmonary embolism in adults", section on 'Nomenclature'.)
In patients with SSPE, the incidence of VTE recurrence is unclear but may be higher than
that in the general population. While older retrospective studies suggested minimal
recurrence, studies were flawed [55-57]. However, in the largest prospective study to date
of 292 patients with isolated SSPE and no lower-extremity DVT who were managed without
anticoagulation, the recurrence rate was 3.1 percent at 90 days, (ie, higher than the
expected rate in the general population of approximately 1 percent or less) [58]. Rates were
higher in those with multiple SSPEs compared with a single isolated PE (5.7 versus 2.1
percent) and higher in older patients compared with those younger than 65 years (5.5
versus 1.8 percent). No fatalities were reported. However, this study was stopped early for
benefit, which may have influenced the results.
Whether or not patients with SSPE should be anticoagulated is controversial [9,59]. Practice
varies widely; some experts anticoagulate all patients with SSPE, regardless of whether or
not symptoms are present, while other experts avoid anticoagulation in a minority of
individuals (especially if a more convincing etiology is discovered on CT for the patients'
symptoms) [52].
Our approach to anticoagulating patients with SSPE is the following:
● We believe that most patients with SSPE should be anticoagulated similarly to those
who present with symptomatic or large lobar defects [5,9]. This is particularly
important when VTE is unprovoked and persistent risk factors for VTE such as active
cancer and acute hospitalization with prolonged immobility, are present; defects are
multiple; symptoms are present; and/or when patients have limited cardiorespiratory
reserve. (See "Venous thromboembolism: Anticoagulation after initial management"
and "Venous thromboembolism: Initiation of anticoagulation".)
The optimal duration of anticoagulation is unknown but similar to patients with

segmental or lobar PE, patients with SSPE should be treated for a minimum of three
months. Anticoagulant therapy beyond that period should be individualized, the
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details of which are discussed separately. (See "Venous thromboembolism: Initiation

of anticoagulation" and "Selecting adult patients with lower extremity deep venous
thrombosis and pulmonary embolism for indefinite anticoagulation", section on
'Incidental subsegmental PE without identifiable risk factors'.)
● Experts also agree that a small subset of patients with a single small defect (ie, seen
on one image) in whom there is no evidence of proximal lower extremity DVT or
evidence of thrombus elsewhere (eg, upper extremity clot) may reasonably opt for no
anticoagulation, provided the risk of recurrence is considered low and patients are
monitored appropriately [9].
Additional findings that may support this decision include those in whom a false
positive test is suspected, the absence of persistent risk factors, those with preserved
baseline cardiorespiratory function, and/or those in whom a low pretest probability
and normal D-dimer is present.
When clinical surveillance is chosen, we suggest serial testing with bilateral proximal
compression ultrasonography (CUS) of the lower extremities in two weeks to look for
evidence of proximal thrombus. We also have a low threshold to repeat diagnostic
imaging for PE should symptoms persist or recur. This strategy is based upon the
rationale that serial CUS has been reported to be safe in patients with nondiagnostic
testing for PE (eg, indeterminate or low probability ventilation perfusion scanning);
details regarding this strategy are described separately. (See "Clinical presentation,
embolism", section on 'Lower-extremity ultrasound with Doppler'.)
Despite support for this strategy, many clinicians are adopting the practice [60].
Inferior vena cava filter — In most patients, an inferior vena cava (IVC) filter is not
necessary. For most patients with PE in whom anticoagulation is contraindicated, or
patients in whom the risk of bleeding is unacceptably high, IVC filter should be placed.
Similarly, an IVC filter is appropriate in patients who develop contraindications while on
anticoagulation; however, placement in this population depends upon the planned
duration of anticoagulation and risk of recurrence when anticoagulation is discontinued.
Another more unusual indication for an IVC filter is recurrence despite therapeutic
anticoagulation; a decision may be more difficult in patients who recur quickly after the
onset of anticoagulation. Retrievable filters should be used such that once the
contraindication has resolved, the filter can be removed and patients should be
14 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

anticoagulated. The efficacy of IVC filters, their placement and complications, are presented
separately. (See "Placement of vena cava filters and their complications" and 'Inferior vena
cava filters' below and "Overview of the treatment of proximal and distal lower extremity
deep vein thrombosis (DVT)", section on 'Inferior vena cava filter'.)
When contraindications to anticoagulation are present in acute PE, an IVC filter should be
placed even in the absence of proven lower extremity thrombus. Thrombus may remain
undetected in the pelvis or calf veins or clot can quickly reform in the leg veins after
embolization.
However, the decision to place an IVC filter, most of which are infrarenal, is modified in the
following settings:
● If the patient has confirmed extensive upper extremity thrombosis in the absence of
lower extremity thrombosis, an IVC filter will not be effective; and a superior vena
caval filter may be useful.
● If the thrombus is in the renal vein (identified by the initial CT angiogram or during
placement of the IVC filter), a suprarenal filter is appropriate.
Data describing outcomes in patients with PE who have IVC filters placed are limited:
● A randomized trial (PREPIC2) reported outcomes in 399 patients with severe PE (eg,
older patients >75 years, active cancer, signs of right ventricle dysfunction, chronic
respiratory insufficiency) who received either standard anticoagulation alone or
anticoagulation plus an IVC filter that was retrieved at three months [61]. At three
months, the addition of an IVC filter to anticoagulation did not alter the rate of PE
recurrence (1.5 versus 3 percent), DVT recurrence (0.5 percent), or mortality (7.5
versus 6 percent). The lack of benefit associated with IVC filter placement was
persistent at six months. The rate of filter complications (eg, thrombosis) was low (<2
percent).
● Data derived from the Nationwide Inpatient Sample reported that the insertion of an
IVC filter in hemodynamically stable patients with PE did not improve in-hospital
mortality but was associated with a lower in-hospital case fatality rate among
unstable patients who received thrombolytic therapy (8 versus 18 percent) as well as
unstable patients who did not receive thrombolytic therapy (33 versus 51 percent)
[62,63]. Another database analysis of over 13,000 patients with PE who were treated
with either thrombolytic or anticoagulant therapy reported a reduction in in-hospital
15 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

mortality in those who were adjunctively treated with an IVC filter compared with
those who did not receive a filter (3 versus 5 percent) [64]. However, both of these
studies are intrinsically flawed.
One of the frequent anecdotal indication uses of IVC filter placement is to prevent follow-up
PE in patients who have large clot burden in the pulmonary arteries with proximal DVT.
Most of these patients may be in the intermediate risk PE category. Such practices should
ideally be avoided, and if there is clinical concern, a multidisciplinary approach with PERT
team and potential treatment with catheter-based treatments (PE or DVT) can be
considered.
Hemodynamically unstable patients — In patients with PE who are hemodynamically

unstable or who become unstable due to recurrence despite anticoagulation, we suggest
more aggressive therapies (ie, reperfusion therapies) than anticoagulation including the
following ( algorithm 1A-B):
● Thrombolytic therapy is indicated in most patients, provided there is no

contraindication ( table 7) (see "Approach to thrombolytic (fibrinolytic) therapy in
acute pulmonary embolism: Patient selection and administration", section on
'Hemodynamically unstable patients (high-risk pulmonary embolism)' and "Approach
to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection
and administration", section on 'Systemic infusion (full-dose thrombolytic)')
● Embolectomy is appropriate for those in whom thrombolysis is either contraindicated

or unsuccessful (surgical or catheter-based) (see 'Embolectomy' below)
Reperfusion therapy
Thrombolytic therapy — Systemic thrombolytic therapy is a widely accepted

treatment for patients with PE who present with, or whose course is complicated by,
hemodynamic instability. This therapy can be delivered more quickly than can be done via a
catheter-based method; if there are no contraindications to systemic thrombolysis and the
indication for reperfusion therapy is clear, the patient should not wait until an operator or
catheterization service lab is available. Catheter-directed thrombus removal with or without
thrombolysis can also be administered in select patients (eg, those at high risk of bleeding
and those who have failed systemic thrombolysis). The indications, contraindications,
agents, administration, and outcomes of systemic and catheter-directed thrombolysis are
discussed separately. (See "Approach to thrombolytic (fibrinolytic) therapy in acute
pulmonary embolism: Patient selection and administration" and 'Catheter-directed
16 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

modalities' below.)
For those in whom systemic thrombolysis is unsuccessful, the optimal therapy is unknown.
Options include repeat systemic thrombolysis, catheter-directed thrombolysis, or catheter
or surgical embolectomy, the choice of which is dependent upon available resources and
local expertise. (See 'Embolectomy' below.)
A prediction score for the risk of major bleeding during thrombolysis ("BACS score")has
been proposed but requires further validation before it can be routinely used [65].
Embolectomy — Embolectomy is indicated in patients with hemodynamically

unstable PE in whom thrombolytic therapy is contraindicated. It is also a therapeutic option
in those who fail thrombolysis. Emboli can be removed surgically or using a catheter. The
choice between these options depends upon available expertise, the presence or absence
of a known diagnosis of PE, underlying comorbidities, and the anticipated response to such
therapies. As an example, when a patient has severe hemodynamic instability and standard
dose thrombolysis is contraindicated, catheter-directed techniques may be preferred if the
expertise is available. One advantage of this approach is that both diagnostic and
therapeutic interventions can be applied simultaneously.
Catheter-directed modalities — Several catheter-directed techniques are

available. Studies have been limited by small sample size and the inclusion of
heterogeneous populations (patients who are hemodynamically stable and unstable,
patients with and without contraindications to thrombolysis) as well as the adjunctive
administration of catheter-directed thrombolytic agents. Nearly all modern-day catheter-
directed thrombolysis trials have utilized tissue plasminogen activator (tPA). None has been
demonstrated to have superiority over the other, such that the choice of technique is
institution-dependent; an absolute contraindication to a thrombolytic agent means that if a
catheter-directed technique is utilized, a catheter-directed clot extraction (ie, embolectomy)
can be used. In our experience, catheter-directed techniques are most commonly utilized in
patients with intermediate-high risk PE, although there is some experience with high-risk
PE.
Options include:
● Ultrasound-assisted thrombolysis – Catheter-directed high frequency ultrasound

can enable the thrombolytic agent to better penetrate the embolus. Without
thrombolytics, the technique has no proven benefit. This is the technique that is best
supported by clinical trial data which are discussed separately [66]. (See "Approach to
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administration", section on 'Catheter-directed approaches' and "Approach to
administration", section on 'Catheter-directed thrombolytic therapy'.)
● Rheolytic embolectomy – Rheolytic embolectomy injects pressurized saline through

the catheter's distal tip while macerated thrombus is aspirated through a catheter
port [67-72]. In a series of 16 patients with massive or submassive PE who underwent
rheolytic embolectomy, resolution of symptoms and improvement in right ventricle
dysfunction were achieved in all patients [71]. There were no in-hospital mortalities.
Complications occurred in three patients (20 percent), two with acute kidney injury
and one with an intraoperative cardiac arrest. Clinical success due to the intervention
alone was unclear because two thirds of the cohort also received catheter-directed
thrombolysis.
Because the catheter is large, the major disadvantage of rheolytic devices is that a
venous cut-down (venotomy) is often required for insertion, which increases the risk
of bleeding at the insertion site. In addition, the release of adenosine from disrupted
platelets can lead to bradycardia, vasospasm, and hypoxia; similarly, red blood cell
fragmentation can result in hemoglobinuria. These and other side effects have led to
a boxed warning from regulatory agencies.
● Rotational embolectomy – A rotating device at the catheter tip can be used to

fragment the thrombus, while fragmented clot is continuously aspirated [73-77]. In a
series of 18 patients with shock due to PE, clinical success was achieved in 16 cases
(89 percent), defined as improvement in oxygenation and blood pressure. The
remaining patients had complications (eg, hemorrhage) and one patient died from
refractory shock [75]. Typically, rotational devices do not require venotomy.
● Suction embolectomy – Thrombus can be manually aspirated through a large-lumen

catheter using an aspiration syringe and a hemostatic valve [78,79]. In one study of 63
patients with mostly hemodynamically unstable PE who underwent suction
embolectomy, 88 percent had a clinically significant reduction in clot burden and
pulmonary artery pressure [79]. Six percent of patients died and 14 percent had major
bleeding. Clinical success due to the intervention alone was unclear because all
patients also received catheter-directed thrombolysis.
Technical difficulties with suction devices have limited their use but newer devices
18 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

may be more successful [32,80-82]. As an example, in a study (FLARE), 106 patients

with documented PE and RV dysfunction (ie, intermediate risk PE), aspiration
thrombectomy with a newer device resulted in improvement in RV function and
pulmonary artery pressure with a complication rate of only 4 percent [32]. There was
one major bleed. Another retrospective study suggested improved in-hospital
mortality and decreased ICU length of stay for patients with acute, central PE with a
flow retrieval suction device [81].
More advanced catheters have been used for the removal of soft, fresh thrombi or for
use during extracorporeal bypass. This applies most readily to large thromboemboli in
the IVC, or right heart chambers. Such devices cannot easily access the pulmonary
arteries to suction more distal emboli [83].
● Thrombus fragmentation – Mechanical disruption of the thrombus can be achieved

by manually rotating a standard pigtail or balloon angioplasty catheter into the
thrombus; small fragments move distally and thereby result in reduced pulmonary
vascular resistance [74,84,85]. While older studies report improved hemodynamic
indices with fragmentation alone, newer studies have reported efficacy when
fragmentation is combined with angioplasty, aspiration, and catheter-directed
thrombolysis [86]. Although rare, catheter-fragmentation can increase pulmonary
vascular pressures likely via embolization of larger fragments into the distal branches
of the pulmonary vascular bed [87,88]. Consequently, aspiration of fragments is
frequently concurrently performed to deal with this complication.
Common to all catheter-assisted embolectomy techniques is the risk of pulmonary artery

perforation; although rare, it can lead to pericardial tamponade and life-threatening
hemoptysis, and is frequently catastrophic. Additional complications include hemorrhage
and infection of venipuncture sites, worsening hemodynamic instability, cardiac arrest, and
death, as well as device-specific adverse effects (listed above). Hemorrhagic side effects can
be exacerbated by the co-administration of thrombolytic therapy.
Surgical embolectomy — The usual indication for surgical embolectomy is

hemodynamic instability due to acute PE for patients in whom thrombolysis (systemic or
catheter-directed) is contraindicated, and is an option in those in whom thrombolysis has
failed [89-92]. Additional indications may include echocardiographic evidence of an
embolus trapped within a patent foramen ovale, or present in the right atrium, or right
ventricle [93]. Surgical embolectomy is typically limited to large medical centers because an
experienced surgeon and cardiopulmonary bypass are required. It has a high mortality,
19 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

particularly in the older patient (2 to 46 percent) [89-92,94-102]. Proximal emboli are

amenable to surgical removal (ie, right ventricle, main pulmonary artery [PA], and
extrapulmonary branches of the PA), whereas distal thrombus generally is not amenable to
surgery (eg, intrapulmonary branches of the PA).
In a retrospective database study, there was no difference in 30-day mortality with the 257
patients who underwent surgical embolectomy compared with 1854 patients with PE who
underwent thrombolysis (15 versus 13 percent) [103]. In an observational study of 40
patients with PE who had failed systemic thrombolysis, patients who underwent surgical
embolectomy had fewer recurrent PE compared with patients who had repeat thrombolysis
(0 versus 35 percent) [95]. In addition, there were fewer deaths and fewer major bleeding
complications associated with surgical embolectomy, which did not achieve statistical
significance. In another series of 115 patients who underwent surgical embolectomy,
compared with patients who had stable PE, those with unstable PE had a higher operative
mortality (10 versus 4 percent) and worse survival (75 versus 93 percent) [99]. Another
retrospective series reported an in hospital mortality of only 2 percent and immediate
improvement of right ventricle pressures that persisted at 30 months [92].
Transesophageal echocardiography (TEE) should be performed before or during

embolectomy to look for extrapulmonary thrombi (eg, in the right atrium, right ventricle, or
vena cava). In a series of 50 patients with PE, intraoperative TEE detected extrapulmonary
thrombi in 13 patients (26 percent), which altered the surgical management of five patients
(10 percent) [104].
Cardiac arrest upon presentation predicts mortality from surgical embolectomy

[89,105-108]. In one study of 36 patients with shock due to acute PE, but without cardiac
arrest, the operative mortality associated with surgical embolectomy was 3 percent [106].
In contrast, operative mortality was 75 percent among patients with acute PE who were
resuscitated from a cardiac arrest and then underwent surgical embolectomy [106,107].
Complications include those associated with cardiac surgery and anesthesia, as well as
embolectomy-specific complications such as perforation of the pulmonary artery and
cardiac arrest. (See "Postoperative complications among patients undergoing cardiac
surgery".)
Extracorporeal membrane oxygenation — Venoarterial extracorporeal membrane

oxygenation (V-A ECMO) has a growing role in management of patients with PE. V-A ECMO
can be used as a sole therapy or bridge to definitive treatment (eg, surgical embolectomy
20 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

or catheter-based treatments) in patients with PE. VA-ECMO can also be used as an initial
strategy in patients with massive PE in whom systemic thrombolysis is contraindicated.
Further details are provided separately. (See "Extracorporeal life support in adults in the
intensive care unit: Overview" and "Extracorporeal life support in adults: Management of
venoarterial extracorporeal membrane oxygenation (V-A ECMO)".)
Special populations — In general, the initial approach to the treatment of PE as well as the
treatment of life-threatening PE in special populations are similar to that in the general
population (see 'Initial approach and resuscitation' above and 'Hemodynamically unstable
patients' above). However, definitive therapy may differ in hemodynamically stable patients
with malignancy, pregnancy, and heparin-induced thrombocytopenia.
Patients with malignancy — In hemodynamically stable patients with malignancy and

PE, LMW heparin and some of the direct oral anticoagulants, edoxaban and apixaban, are
used as anticoagulants. The details of supporting trials are discussed separately. (See
"Anticoagulation therapy for venous thromboembolism (lower extremity venous
thrombosis and pulmonary embolism) in adult patients with malignancy".)
Patients who are pregnant — For most pregnant women with hemodynamically stable
PE, adjusted-dose subcutaneous LMW heparin is the preferred agent for initial and long-
term anticoagulation due to its favorable fetal safety profile ( table 8). Treatment of PE in
pregnancy is discussed in detail separately. (See "Use of anticoagulants during pregnancy
and postpartum" and "Venous thromboembolism in pregnancy and postpartum:
Treatment".)
Patients with heparin-induced thrombocytopenia — For patients with PE and heparin-

induced thrombocytopenia (HIT), all forms of heparin are contraindicated (eg,
unfractionated and LMW heparin). Immediate anticoagulation with a fast-acting non
heparin anticoagulant (eg, argatroban) is indicated. The diagnosis and management of
patients with HIT are discussed in detail separately. (See "Clinical presentation and
diagnosis of heparin-induced thrombocytopenia" and "Management of heparin-induced
thrombocytopenia".)
Inherited thrombophilias — In many cases, the presence of an inherited thrombophilia

does not appreciably alter treatment decisions such as choice of an anticoagulant, but
there may be specific circumstances in which the thrombophilia does affect management
(eg, need for antithrombin [AT] administration in some individuals with AT deficiency).
Details are presented in separate topic reviews:
21 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

● Factor V Leiden – (See "Factor V Leiden and activated protein C resistance", section on
'Patients with VTE'.)
● Prothrombin G20210A mutation – (See "Prothrombin G20210A", section on 'Patients
with VTE'.)
● Protein S deficiency – (See "Protein S deficiency", section on 'Patients with VTE'.)
● Protein C deficiency – (See "Protein C deficiency", section on 'Thromboembolism
management'.)
● Antithrombin deficiency – (See "Antithrombin deficiency", section on 'VTE treatment
(hereditary deficiency)'.)
Antiphospholipid syndrome — Considerations with treatment of VTE in patients with

antiphospholipid syndrome are presented separately (eg, direct oral anticoagulants are
generally not administered). (See "Management of antiphospholipid syndrome".)
ADJUNCTIVE THERAPIES
Therapies that can be added as an adjunct to anticoagulation in patients with PE are

discussed in the sections below.
General medical — Patients with PE should always receive supportive care with analgesia,
intravenous fluids, and oxygen, as clinically indicated (see 'Initial therapies' above). When
present, pleuritic pain from PE is best treated with scheduled medications, usually
acetaminophen or nonsteroidal antiinflammatories, and narcotics. The choice among these
agents should be individualized. Failure to wean supportive therapies should prompt
consideration of complications (eg, pneumonia or recurrence).
Ambulation — When feasible, early ambulation should be encouraged in most patients

with acute PE, provided the patient is definitively treated. For those with significant clot
burden and significant PE, bedrest may be needed for the first 12 to 24 hours to ensure
therapeutic anticoagulation. Typically, ambulation is limited by the need for postoperative
bedrest or by comorbidities including severe symptoms of concurrent deep venous
thrombosis (DVT) or hypoxia . (See "Overview of the treatment of proximal and distal lower
extremity deep vein thrombosis (DVT)", section on 'Ambulation'.)
Elastic graduated compression stockings — Elastic graduated compression stockings

(GCS) are not routinely used in patients with DVT to prevent post-thrombotic syndrome
(PTS). Detailed discussion of the manifestations and treatment of post-thrombotic
syndrome (PTS) and role of GCS in the prevention of PTS are discussed separately. (See
22 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

"Overview of the treatment of proximal and distal lower extremity deep vein thrombosis
(DVT)", section on 'Graduated compression stockings' and "Post-thrombotic (postphlebitic)
syndrome".)
Inferior vena cava filters — In patients with acute PE, the primary indication for inferior
vena cava (IVC) filter placement is when anticoagulation is contraindicated and when
recurrent PE occurs despite therapeutic anticoagulation. However, it may be appropriate as
an adjunct to anticoagulation in patients in whom another embolic event would be poorly
tolerated (eg, poor cardiopulmonary reserve, or severe hemodynamic or respiratory
compromise), although clinical data are lacking. Filters are not routinely placed as an
adjunct in patients with PE. (See 'Management of recurrence on therapy' below.)
Filter placement is also sometimes used in patients with recurrence despite therapeutic
anticoagulation or in those with a high risk of recurrence in whom it is anticipated that
anticoagulation may need to be discontinued because of bleeding. Examples include
patients at moderate risk of bleeding who cannot receive fresh frozen plasma or red cells
(eg, due to religious preference), and patients with metastatic malignancy who are at a high
risk for both recurrence and bleeding.
Although filters are not routinely placed as an adjunct in patients with PE, some experts
place them in patients at risk of decompensation due to cardiorespiratory compromise. We
agree that the adjunctive use of filters should not be routine, but placement may be
individualized and should take into consideration the risk of recurrence and bleeding,
patient preferences, institutional expertise, medical morbidities, and surgical
complications.
IVC filter placement in patients with contraindications to anticoagulation and filter

complications are reviewed separately. (See "Placement of vena cava filters and their
complications".)
A femoral IV access line with a "built-in" IVC filter that can be opened when the line is
placed and collapsed and removed when the line is removed has been found useful in high
risk patients who cannot be treated with anticoagulants [109].
PROGNOSIS
Morbidity and mortality — Prognosis from PE is variable. Accurate estimates have been
limited by data that are mostly derived from older studies, registries, and hospital
23 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

discharge records collected from heterogeneous populations of patients. As an example, a

patient with a single, asymptomatic, subsegmental PE (SSPE) likely has a different
prognosis than a patient with massive PE and shock. However, in general, if left untreated,
PE is associated with an overall mortality of up to 30 percent compared with 2 to 11 percent
in those treated with anticoagulation [1,4,57,110-116]. PE-related mortality may be
decreasing with reported rates falling from 3.3 percent (2001 to 2005) to 1.8 percent (2010
to 2013) in one study and from 17 to 10 percent in another study [116,117]. Another study
that derived data from the World Health Organization (WHO) mortality database reported a
similar decrease in deaths from 12.8 per 100,000 to 6.6 per 100,000 between 2000 and
2015 [118].
Early — We consider early outcomes as those occurring within the first three months after
the diagnosis of PE. The highest risk for events occurs within the first seven days; death and
morbidity during this period are most commonly due to shock and recurrent PE.
● Shock (ie, hemodynamic collapse) – Shock can be the initial presentation or an early
complication of PE (8 percent of patients). It is the most common cause of early death,
particularly in the first seven days, and when present, is associated with a 30 to 50
percent risk of death [112,113,119]. The high risk of death, which is greatest in the
first two hours of presentation, is the rationale for the consideration of reperfusion
therapy (thrombolytics/embolectomy) rather than anticoagulation. The risk remains
elevated for 72 hours or more, such that close observation of this population, as well
as those considered at risk of hemodynamic collapse (eg, right ventricle dysfunction),
is prudent during hospitalization. (See "Approach to thrombolytic (fibrinolytic) therapy
in acute pulmonary embolism: Patient selection and administration" and
'Embolectomy' above and 'Shock and right ventricular dysfunction' below.)
● Recurrence – The risk of recurrence (deep venous thrombosis [DVT] and PE) is
greatest in the first two weeks, and declines thereafter. The cumulative proportion of
patients with early recurrence while on anticoagulant therapy amounts to 2 percent at
two weeks, and 6 percent at three months [120-122]. Factors including cancer and
failure to rapidly achieve therapeutic levels of anticoagulation are major predictors of
increased risk of recurrence during this period, the management of which is discussed
below [123,124]. (See 'Management of recurrence on therapy' below.)
● Pleuritic/alveolitis and pneumonia – In the one to two weeks following diagnosis,

patients may deteriorate and develop worsening oxygenation, respiratory failure,
hypotension, pain, and/or fever that suggests an evolving infarct and/or
24 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

superimposed pneumonia. Although chest radiography may reveal collapse,

atelectasis, or a pleural effusion to support the presence of an evolving infarct and/or
superimposed pneumonia, these patients should undergo repeat definitive imaging
(preferably with the original diagnostic imaging modality) to distinguish these
diagnoses from recurrent PE. Patients without recurrence should be treated
symptomatically with supplemental oxygen, analgesics, and intravenous fluids, and
ventilation, vasopressors and/or antibiotics, as indicated.
● Stroke – Prospective and retrospective studies have suggested an increased risk of

stroke, thought to be due to paradoxical embolism via a patent foramen ovale (PFO),
in patients with acute PE [125-129]. Prevalence rates of stroke have ranged from 7 to
50 percent (averaging <17 percent), with higher rates in those with PE who also have a
PFO (21 to 64 percent, averaging <33 percent). Best illustrating this risk for stroke is a
prospective study of 361 patients with acute PE who underwent contrast transthoracic
echocardiography (TTE) and magnetic resonance imaging (MRI) of the brain (for silent
or symptomatic stroke) within ten days after the diagnosis of PE [129]. Stroke was
diagnosed in 7.6 percent and PFO in 13 percent of patients with acute PE. Rates of
stroke were higher in those who had a PFO compared with those who did not have a
PFO (21.4 versus 5.5 percent; relative risk 3.5, 95% CI 1.62-8.67). However, nine
patients were excluded from the analysis due to inconclusive TTE or MRI testing and
the rate of PFO was lower than that in the general population (approximately 25 to 30
percent) [130] suggesting that these results are flawed. Further studies are
recommended before we can support a recommendation to routinely perform
contrast echocardiography (transthoracic or transesophageal) or MRI imaging in
patients with acute PE who have no symptoms of stroke [131]. Accordingly, we prefer
a symptom-directed approach such that vigilant surveillance for neurologic symptoms
is appropriate in those with acute PE and the presence of stroke should prompt a
search for a PFO. Whether the discovery of a PFO with PE and stroke should prompt
indefinite anticoagulation and/or PFO closure is also unknown such that a
multidisciplinary approach with a pulmonologist, neurologist, and cardiologist is
prudent. Management of patients with stroke and PFO is discussed separately. (See
"Patent foramen ovale" and "Initial assessment and management of acute stroke" and
"Early antithrombotic treatment of acute ischemic stroke and transient ischemic
attack" and "Long-term antithrombotic therapy for the secondary prevention of
ischemic stroke".)
Late — The incidence of late events, at three months or later following a diagnosis of PE,
25 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

ranges from 9 to 32 percent, with increased mortality reported for as long as 30 years
[1,4,114,115,132,133]. Late mortality is mostly due to predisposing comorbidities, and less
commonly due to recurrent thromboembolism or chronic thromboembolic pulmonary
hypertension. As examples:
● Mortality – In one retrospective study of 1023 patients with PE, the five-year
cumulative mortality rate was 32 percent [133]. Among those who died, only 5 percent
of the deaths were due to PE, 64 percent were due to non-cardiovascular causes (eg,
malignancy, sepsis), and 31 percent were due to cardiovascular causes other than PE
(eg, myocardial infarction, heart failure, and stroke). One year follow-up of patients in
the prospective investigation of PE diagnosis (PIOPED) cohort revealed similar
findings [1].
Another database analysis of over 128,000 patients with venous thromboembolism

reported a three-fold increase in mortality at 30 years in patients with PE when
compared with age and sex-matched controls who did not have PE during the same
period [132].
Combined data from two prospective studies of 748 patients with PE reported that
those with SSPE had similar rates of mortality (10 versus 7 percent) and recurrence (4
versus 3 percent) at three months when compared with patients with proximal PE
[57]. Death in patients with SSPE was largely determined by comorbidities including
malignancy, increasing age, male sex, chronic obstructive pulmonary disease, and
heart failure.
● Recurrence – The cumulative rate of late recurrence has been reported to be 8

percent at six months, 13 percent at one year, 23 percent at five years, and 30 percent
at 10 years [120-122]. Rates of recurrence vary according to the population studied
with comparable rates reported in those with SSPE and proximal PE at three months
(4 versus 3 percent) [57]. However, in general, the rate is lowered with therapeutic
anticoagulation, and increased by the presence of select risk factors (eg, unprovoked
PE, malignancy), which are discussed separately. (See "Selecting adult patients with
lower extremity deep venous thrombosis and pulmonary embolism for indefinite
anticoagulation".)
● Chronic thromboembolic disease (CTED) and chronic thromboembolic pulmonary

hypertension (CTEPH) – CTED and CTEPH are unusual complications of PE that
typically present with progressive dyspnea within two years of the initial event. The
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clinical manifestations and diagnosis of CTED and CTEPH are discussed separately.
(See "Epidemiology, pathogenesis, clinical manifestations and diagnosis of chronic
thromboembolic pulmonary hypertension".)
● Other – PE has been associated with an increased risk for subsequent cardiovascular
events and atrial fibrillation [134]. (See "Overview of the causes of venous
thrombosis", section on 'VTE and atherosclerotic disease'.)
For most patients with dyspnea, exercise capacity and quality of life improve over the
first year. Predictors of reduced improvement over time in one prospective study of
100 patients with acute PE were female sex, higher body mass index, prior lung
disease, and higher systolic pulmonary artery pressure on day 10 echocardiography
[135].
The likelihood of complications and death from PE may be differentially dependent upon
the presence or absence of provoking risk factors at the time of diagnosis. A three-year
observational study that followed 308 patients with PE found that patients with unprovoked
PE were more likely to develop recurrence, CTEPH, malignancy, and cardiovascular events;
in contrast, patients who had provoked PE had a higher risk of death over the seven-year
study period [136].
Prognostic factors — Poor prognostic factors in patients diagnosed with PE are discussed
in the sections below.
Shock and right ventricular dysfunction — Several clinical, radiologic, and laboratory
markers of right ventricular (RV) dysfunction have been identified as poor prognosticators
in patients with PE.
● Clinical – The presence of clinical shock, which is due to severe RV failure, consistently
predicts death in patients diagnosed with PE, the details of which are discussed above.
(See 'Early' above.)
● Radiologic (echocardiography and CT pulmonary angiography [CTPA]) – RV

dysfunction assessed by echocardiography or CT pulmonary angiography (CTPA), is
associated with increased mortality [137-143], although we believe that
echocardiography is more reliable than CTPA.
• One meta-analysis of seven studies that included 3395 normotensive and

hypotensive patients with PE reported that RV dysfunction was associated with a
two-fold increase in PE-related in-hospital mortality [143]. However, a subgroup
27 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

analysis of normotensive patients found that RV dysfunction on echocardiography

or CT correlated poorly with mortality, suggesting that it is symptomatic RV
dysfunction that predicts death.
• In a study of 1950 patients diagnosed and treated with PE in a prospective

multicenter trial, larger pulmonary trunk diameter on CTPA was associated with
higher mortality during the treatment period of 3 to 6 months (OR 2.8, 95% CI
1.3-5.7) and at one year (OR 2.3, 95% CI 1.4-4.0) [144]. An association with right
ventricular dysfunction was not observed.
RV dysfunction may also predict recurrent venous thromboembolism (VTE). In one

prospective observational study of 301 patients with PE, those with persistent RV
dysfunction on echocardiography at three months following diagnosis had a four-fold
increased risk of recurrent VTE when compared with patients without RV dysfunction
or with patients whose RV dysfunction resolved prior to discharge (9 versus 3 and 1
percent patient-years) [145].
Echocardiographic findings of RV dysfunction in patients with PE are discussed

separately. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant
adult with suspected acute pulmonary embolism", section on 'Echocardiography' and
"Echocardiographic assessment of the right heart", section on 'Conditions associated
with right ventricular pathology'.)
● Laboratory markers – Biochemical markers of RV dysfunction at diagnosis include

elevated levels of the following:
• Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-
proBNP) from RV strain
• Troponin-I and T levels due to RV-associated myocardial damage
In general, elevated BNP, NT-proBNP, and troponin have consistently been associated
with an increased risk of death or other adverse outcomes in patients with PE
[137,146-155]. However, the optimal cut-off values for risk stratification are unknown.
In hemodynamically stable patients, these markers are poor predictors of death when
elevated but consistently identify a benign clinical course when normal or low
[139,147,150,151,153,155-158].
BNP and NT-proBNP as biomarkers of left heart failure and the differential diagnosis
of elevated troponins, other than acute coronary syndrome, are discussed in detail
28 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

separately. (See "Natriuretic peptide measurement in heart failure" and "Elevated

cardiac troponin concentration in the absence of an acute coronary syndrome".)
Right ventricle thrombus — Mobile right heart thrombi are seen in approximately 4
percent of patients with PE, by either echocardiography or CT, and the proportion is higher
among patients who are critically ill (up to 18 percent) [159,160]. The presence of right
heart thrombus has been shown in several studies to be associated with RV dysfunction
and high early mortality [159,161,162]. As an example, data from an international registry
of patients with PE reported that, compared with patients without RV thrombus, patients
with RV thrombus had a higher 14-day mortality (21 versus 11 percent) and three-month
mortality (29 versus 16 percent) [159].
Deep vein thrombosis — Patients with PE and a coexisting DVT are at increased risk for
death. As an example, one prospective study of 707 patients with PE reported increased all-
cause mortality (adjusted hazard ratio [HR] 2.05, 95% CI 1.24-3.38) and PE-specific mortality
(adjusted HR 4.25, 95% CI 1.61-11.25) at three months in patients with concomitant DVT
compared with those without concomitant DVT [39].
Other — Additional predictors of poor prognosis that require further validation include
the following:
● Hyponatremia (<130 mmol/L) and indicators of renal dysfunction [163-165]

● Serum lactate (>2 mmol/L) [166,167]
● White blood cell count (>12.6 x 109/L) [168]
● The Charlson co-morbidity index ≥1 [169]
● Residual pulmonary vascular obstruction [170,171]
● Older age ≥65 years [172]
● Poor adherence to guidelines [173]
● Tachycardia on admission [174]
● Acute kidney injury [175]
Prognostic models — Prognostic models can facilitate the decision to treat patients as an
outpatient and identify those that require vigilant monitoring as an inpatient. Their role in
management outside of this context is unclear. (See 'Outpatient anticoagulation' above.)
Several prognostic models have been derived in patients with acute PE, of which the
Pulmonary Embolism Severity Index (PESI) and the simplified PESI (sPESI) are the most well-
known ( table 6) [176-180]. While PESI and sPESI predict death, newer composite models
predict death and/or complications (recurrent PE, hemodynamic collapse). As examples:
29 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

● PESI – The PESI adds the patient's age to points assigned to ten additional variables
( table 6) [176]: male sex (+10 points), history of cancer (+30 points), heart failure
(+10 points), chronic lung disease (+10 points), pulse ≥110 beats per minute (+20
points), systolic blood pressure <100 mmHg (+30 points), respiratory rate ≥30 breaths
per minute (+20 points), temperature <36 degrees C (+20 points), altered mental
status (+60 points), and arterial oxygen saturation <90 percent (+20 points). The total
score categorizes the patient according to increasing risk for mortality:
• Class I (<66 points)

• Class II (66 to 85 points)
• Class III (86 to 105 points)
• Class IV (106 to 125 points)
• Class V (>125 points)
Patients with class I/II are considered to be at low risk of death, compared with
classes III through V, who are at high risk. The major limitation of the PESI is that it is
difficult to apply in a busy clinical setting because so many variables must be
considered, each with its own weight.
● sPESI – The sPESI assigns one point for each of the following variables: age >80 years,
a history of cancer, chronic cardiopulmonary disease, a heart rate ≥110 beats per
minute, a systolic blood pressure <100 mmHg, and an arterial oxyhemoglobin
saturation <90 percent [181]. A score of zero indicates a low risk for mortality, while a
score of one or more indicates a high risk.
The sPESI may have a prognostic accuracy that is similar to PESI. In a cohort of 995
patients with PE that compared PESI with sPESI, a similar 30-day mortality was
reported in patients classified as low risk (3 versus 1 percent) or high risk (11 percent
each) [181]. Prospective validation of the sPESI is needed.
● Other – A composite model that incorporates sPESI, brain natriuretic peptide (BNP),
cardiac troponin I, and lower limb ultrasound (done within 48 hours of admission) was
derived and validated in a cohort of 848 normotensive patients with acute PE [179].
The combination of a low risk sPESI score and BNP <100 pg/mL identified patients at
low risk of death, hemodynamic collapse, and/or recurrent PE at 30 days (negative
predictive value of 99 to 100 percent). The combination of high risk sPESI, elevated
BNP, elevated troponin I, and concomitant DVT identified patients who were at high
risk of death or complications at 30 days (positive predictive value, 21 to 26 percent).
30 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

Further validation of this model is required before it can be routinely applied in clinical
practice.
Another score ("BOVA score") has also been described but requires further validation
before it can be routinely used [182].
While many of the available prognostic models are sensitive in predicting death from acute
PE, they are not specific. One study of 11 clinical prognostic models reported that although
the sensitivity of some models, including PESI and sPESI, were >89 percent, none had a
specificity greater than 48 percent [183].
MONITORING AND FOLLOW-UP
Patients with PE should be monitored following diagnosis for the following:
● Therapeutic levels of anticoagulation in patients receiving heparin and warfarin –

The most common laboratory test used to monitor unfractionated heparin is the
activated partial thromboplastin time (aPTT) with a target range of 1.5 to 2.5 times the
upper limit of normal. Some experts monitor heparin levels. Warfarin is monitored
using the prothrombin time (PT) ratio usually expressed as the international
normalized ratio (INR) with a goal INR of 2 to 3 (target 2.5). (See "Biology of warfarin
and modulators of INR control".)
Low molecular weight heparin, fondaparinux, and the factor Xa and direct thrombin
inhibitors do not require routine laboratory monitoring. (See "Direct oral
anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and
adverse effects".)
The development of conditions that affect the half-life of the anticoagulant used (eg,
renal failure, pregnancy, weight gain/loss, drug interactions) should also be followed.
● Early complications of PE, predominantly recurrence – In the one to two weeks

following diagnosis, patients may deteriorate and experience recurrence, the
management of which is discussed below. (See 'Management of recurrence on
therapy' below.)
Whether patients should undergo echocardiography (transthoracic or

transesophageal) or MRI of the brain to look for a patent foramen ovale (PFO) or
asymptomatic stroke is unclear. However, symptom-driven evaluation for a PFO and
31 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

stroke is appropriate.
● Late complications of PE including recurrence and chronic thromboembolic

disease (CTED) and chronic thromboembolic pulmonary hypertension (CTEPH) –
At each visit, patients should be monitored for continued resolution of the presenting
manifestations of PE and investigated for new symptoms suggestive of recurrent PE
or deep venous thrombosis [184]. (See "Clinical presentation, evaluation, and
diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)
The development of persistent or progressive dyspnea, particularly during the first

three months to two years of diagnosis, should prompt the clinician to investigate for
the development of CTEPH (affects up to 5 percent of patients). While some clinicians
do not routinely perform follow-up CT, ventilation perfusion scans, or
echocardiography, clinicians should have a low threshold to repeat diagnostic imaging
if recurrence or CTEPH is suggested. In addition, some experts evaluate for CTEPH in
those with risk factors. The risks, clinical manifestations and diagnosis of CTEPH are
discussed separately. (See "Epidemiology, pathogenesis, clinical manifestations and
diagnosis of chronic thromboembolic pulmonary hypertension".)
● Complications of the therapy itself including bleeding and adverse effects of

medications or devices – Patients should be monitored for complications including
bleeding (anticoagulants), skin necrosis (warfarin), osteoporosis (heparin),
thrombocytopenia (heparin), and device migration (caval filters). Details regarding the
individual complications of such therapies are discussed separately. (See "Heparin and
LMW heparin: Dosing and adverse effects" and "Warfarin and other VKAs: Dosing and
adverse effects" and "Direct oral anticoagulants (DOACs) and parenteral direct-acting
anticoagulants: Dosing and adverse effects" and "Placement of vena cava filters and
their complications", section on 'Complications' and 'Embolectomy' above and
"Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient
selection and administration", section on 'Efficacy'.)
● The risk of recurrence and bleeding – The risk of recurrence and bleeding should be
periodically reassessed in patients during and upon completion of therapy to assess
the ongoing need for such treatment. As an example, patients with major bleeding
while on anticoagulation should not continue, whereas those with minor bleeding (eg,
epistaxis) or recurrence should continue to be anticoagulated. The indications for
indefinite anticoagulation are discussed separately. (See "Selecting adult patients with
lower extremity deep venous thrombosis and pulmonary embolism for indefinite
32 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

anticoagulation".)
● The need for device removal – Patients who had an inferior vena cava filter placed
because anticoagulation was contraindicated should, once the contraindication has
resolved, initiate anticoagulant therapy and have the filter retrieved, if feasible. (See
"Placement of vena cava filters and their complications", section on 'Filter retrieval'.)
● The underlying predisposing risk factors for PE – The presence or absence of risk
factors that predisposed the patient to the development of PE (eg, malignancy,
inherited thrombotic disorder, surgery) should be sought and investigated, as
indicated. The evaluation of patients with established venous thromboembolism for
risk factors is discussed separately. (See "Evaluating adult patients with established
venous thromboembolism for acquired and inherited risk factors".)
In some institutions, specialty clinics follow patients with PE (eg, "clot clinic") to ensure
adequate and thorough follow-up, although the benefits of such clinics are unknown.
MANAGEMENT OF RECURRENCE ON THERAPY
Inadequate anticoagulation is the most common reason for recurrent venous

thromboembolism (VTE; PE and/or deep venous thrombosis) while on therapy. Explanations
for subtherapeutic anticoagulation as well as several additional etiologies for recurrence
that should be considered are listed below:
● Subtherapeutic anticoagulation – Subtherapeutic anticoagulation is the most

common reason for recurrence. A detailed history and examination should be
performed to identify factors that contribute to subtherapeutic anticoagulation. These
include:
• Malabsorption (eg, malabsorption syndromes, rivaroxaban should be taken with

food) (see "Overview of nutrient absorption and etiopathogenesis of
malabsorption")
• Discontinuation for an anticipated procedure (see "Perioperative management of
patients receiving anticoagulants")
• Poor compliance
• Altered dose requirement or pharmacokinetics for warfarin (eg, dietary vitamin K),
target-specific oral anticoagulants (eg, drug interactions), or low molecular weight
(LMW) heparin (eg, weight gain)
33 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

• High dose requirement for heparin (eg, increased heparin binding proteins,
aprotinin)
• Incorrect dosing of medication
Consulting a coagulation specialist may be warranted, especially when abnormal

pharmacokinetics or noncompliance for medications that cannot be monitored easily
(eg, target-specific oral anticoagulants, LMW heparin) are suspected. (See "Heparin
and LMW heparin: Dosing and adverse effects", section on 'Heparin
resistance/antithrombin deficiency' and "Direct oral anticoagulants (DOACs) and
parenteral direct-acting anticoagulants: Dosing and adverse effects" and "Biology of
warfarin and modulators of INR control".)
For those subtherapeutic on unfractionated heparin, the dose should be increased to

rapidly achieve therapeutic levels. For patients who are on LMW heparin or factor Xa
and direct thrombin inhibitors in whom subtherapeutic anticoagulation is suspected
but unconfirmed, or for those subtherapeutic on warfarin, switching to a rapid–acting
anticoagulant that can be followed (eg, unfractionated heparin) may be prudent while
investigations are ongoing.
Because new direct thrombin and Xa inhibitors do not require monitoring, it is yet to
be determined whether challenges will emerge with monitoring for therapeutic levels.
● Suboptimal therapy – Therapeutic anticoagulation is the optimal therapy for VTE.

Suboptimal therapies, including inferior vena cava filters and embolectomy or
thrombolysis not followed by anticoagulation, should be apparent to the investigating
clinician. Resumption of therapeutic anticoagulation should be considered in such
cases, when feasible.
● Ongoing prothrombotic stimuli – In patients who develop recurrence despite

therapeutic anticoagulation, a search for conditions associated with high recurrence
rates is prudent. These include malignancy, May-Thurner syndrome, inherited
thrombotic disorders (eg, protein S, protein C, or antithrombin deficiency), and
antiphospholipid syndrome. (See "Evaluating adult patients with established venous
thromboembolism for acquired and inherited risk factors" and "Overview of the
causes of venous thrombosis", section on 'Anatomic risk factors for deep venous
thrombosis'.)
In this population, therapeutic options are limited. We suggest an approach similar to

that performed in patients with recurrent thrombosis who have an underlying
34 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

malignancy. These options include treatment with an LMW heparin for those on
warfarin, escalation of the dose of LMW heparin for those on LMW heparin, and/or
the addition of a vena cava filter. The efficacy of factor Xa and direct thrombin
inhibitors in this population is unstudied. Further details regarding these strategies
are discussed separately. (See "Management of antiphospholipid syndrome", section
on 'Recurrent thromboembolism despite adequate anticoagulation' and
"Anticoagulation therapy for venous thromboembolism (lower extremity venous
thrombosis and pulmonary embolism) in adult patients with malignancy", section on
'Management of recurrence'.)
Recurrence may also be associated with conditions that promote thrombus

propagation (eg, mechanical obstruction of venous flow from pelvic masses or inferior
vena cava filter), or thrombus dissociation (eg, large right ventricular [185] or valvular
thrombus). In such patients, treating the underlying cause or removing mobile
thrombus may be appropriate, when feasible.
● Misdiagnosis – Occasionally, tumor or fat emboli may radiographically mimic PE due

to thrombus, the presentation and management of which are discussed separately.
(See "Pulmonary tumor embolism and lymphangitic carcinomatosis in adults:
Diagnostic evaluation and management" and "Fat embolism syndrome".)
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
35 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topics (see "Patient education: Pulmonary embolism (blood clot in the lung)
(The Basics)")
● Beyond the Basics topics (see "Patient education: Pulmonary embolism (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
● Initial resuscitation – The initial approach to patients with suspected pulmonary

embolism (PE) should focus upon stabilizing the patient while clinical evaluation and
definitive diagnostic testing is ongoing ( algorithm 1A-B). (See 'Initial approach and
resuscitation' above and 'Initial therapies' above.)
• Respiratory and hemodynamic support (see 'Respiratory support' above and

'Hemodynamic support' above):
- Supplemental oxygen should be administered to target an oxygen saturation

≥90 percent.
- Severe hypoxemia, hemodynamic collapse, or respiratory failure should

prompt consideration of mechanical ventilation. When mechanical ventilation
is necessary, we prefer that an expert in cardiovascular anesthesia be
consulted, when feasible, to avoid catastrophic hypotension due to sedation
and positive pressure ventilation.
- For those who require hemodynamic support, we suggest cautious infusions

of intravenous fluid (IVF; 250 to 400 mL of normal saline) rather than larger
volumes (Grade 2C). Vasopressor therapy should be initiated if perfusion fails
to respond to IVF.
Empiric anticoagulation – For patients with suspected PE who are

hemodynamically stable or hemodynamically unstable and successfully
resuscitated, the administration of empiric anticoagulation depends upon the risk
36 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

of bleeding ( table 3), the clinical suspicion for PE (( table 2) (calculator 1)), and
the expected timing of diagnostic tests (see 'Hemodynamically stable' above and
'Empiric anticoagulation' above) :
- For patients with a low risk of bleeding and a high clinical suspicion for PE, we
suggest empiric anticoagulation rather than waiting until definitive diagnostic
tests are completed (Grade 2C). We use a similar approach in those with a
moderate or low clinical suspicion for PE in whom the diagnostic evaluation is
expected to take longer than four hours and 24 hours, respectively.
- We do not anticoagulate patients with absolute contraindications to

anticoagulant therapy or those with an unacceptably high risk of bleeding
(Grade 1C).
- For patients with a moderate risk of bleeding, empiric anticoagulant therapy

may be administered on a case-by-case basis according to the assessed risk-
benefit ratio ( table 3).
- The optimal agent for empiric anticoagulation depends upon hemodynamic

instability, the anticipated need for procedures or thrombolysis, and the
presence of risk factors and comorbidities.
● Definitive therapy for suspected PE – For those with suspected PE, we perform the
following:
In patients with a high clinical suspicion for PE who are hemodynamically unstable
and who have a definitive diagnosis by portable perfusion scanning or a
presumptive diagnosis of PE by bedside echocardiography (because definitive
diagnostic testing is unsafe or not feasible), we suggest systemic thrombolytic
therapy rather than empiric anticoagulation or no therapy (Grade 2C). (See
'Hemodynamically unstable' above.)
• If bedside testing is delayed or unavailable, the use of thrombolytic therapy as a

life-saving measure should be individualized; if not used, the patient should
receive empiric anticoagulation.
• For patients who are hemodynamically unstable and the clinical suspicion is low or
moderate, we suggest empiric anticoagulation similar to that suggested for
patients who are hemodynamically stable; empiric thrombolysis is not justified in
this population.
37 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

• The employment of a multidisciplinary team may be of value in patients who are

unstable due to PE or in select patients with intermediate to high-risk PE.
● Definitive therapy for confirmed PE – For patients in whom the diagnostic

evaluation confirms PE, we suggest an approach that is stratified according to
whether or not the patient is hemodynamically stable or unstable ( algorithm 1A-B).
At any time, the strategy may need to be redirected as complications of PE or therapy
arise. (See 'Definitive therapy' above.)
• Hemodynamically stable low-risk/nonmassive PE – For most hemodynamically

stable patients with PE that is low risk/nonmassive, the following applies (see
'Hemodynamically stable patients' above):
- For those in whom the risk of bleeding is low, we recommend that

anticoagulant therapy be initiated or continued (Grade 1B) ( table 4). (See
'Anticoagulation' above.)
- Outpatient anticoagulation is safe and effective in select patients at low risk of

death ( table 6), provided that they do not have respiratory distress, serious
comorbidities, or requirement for oxygen or narcotics, and that they also have
a good understanding of the risks and benefits of such an approach. (See
'Outpatient anticoagulation' above.)
- Most patients with subsegmental PE should be anticoagulated; however, in a

small select population, observation with serial lower extremity
ultrasonography may be appropriate. (See 'Patients with subsegmental PE'
above.)
- For those who have contraindications to anticoagulation or have an

unacceptably high bleeding risk ( table 3), we suggest that an inferior vena
cava (IVC) filter be placed rather than observation (Grade 2C). (See 'Inferior
vena cava filter' above.)
- For those in whom the risk of bleeding is moderate, therapy should be

individualized according to the risk-benefit ratio and preferences of the
patient.
- In most hemodynamically stable patients, we recommend against

thrombolytic therapy (Grade 1C).
38 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

• Hemodynamically stable intermediate-risk/submassive PE – For most

hemodynamically stable (ie, normotensive) patients with intermediate-
risk/submassive PE, anticoagulation should be administered and patients
monitored closely for deterioration. Examples of such patients include those who
subsequently deteriorate due to recurrent PE, have a large clot burden, severe RV
enlargement/dysfunction, have high oxygen requirement, and/or severely
tachycardic ( table 5). Thrombolysis and/or catheter-based therapies may be
considered on a case-by-case basis when the benefits are assessed by the clinician
to outweigh the risk of hemorrhage (eg, deterioration due to PE). (See "Approach
to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient
selection and administration".)
• Hemodynamically unstable PE – For most patients with hemodynamically

unstable PE, the following applies (see 'Hemodynamically unstable patients'
above):
- No contraindications to thrombolysis – For patients with refractory

hypotension and without contraindications to thrombolysis ( table 7), we
suggest systemic thrombolytic therapy followed by anticoagulation rather
than anticoagulation alone (Grade 2C) ( table 5). We suggest a similar
approach for select patients whose course becomes complicated by
hypotension during anticoagulation in whom the suspicion for recurrent PE
despite anticoagulation is high. (See "Approach to thrombolytic (fibrinolytic)
therapy in acute pulmonary embolism: Patient selection and administration"
and 'Thrombolytic therapy' above.)
- Contraindications to thrombolysis – For those in whom thrombolysis is

contraindicated ( table 7), we suggest catheter or surgical embolectomy
rather than observation (Grade 2C). The choice between these options
depends upon a variety of factors. (See 'Embolectomy' above.)
- Failed thrombolysis – For those in whom systemic thrombolysis is

unsuccessful, the optimal therapy is unknown. Options include repeat
systemic thrombolysis, catheter-directed thrombolysis, or catheter or surgical
embolectomy. Our preference is for catheter-based thrombolysis. However, in
many cases, the choice is dependent upon available resources and local
expertise. (See "Approach to thrombolytic (fibrinolytic) therapy in acute
pulmonary embolism: Patient selection and administration", section on
39 57 ‫ﻣﻦ‬ ‫ ﻡ‬٠٤:٥٠ ،٢٢/٠٤/٤٥

'Hemodynamically unstable patients (high-risk pulmonary embolism)'.)
● Adjunctive therapies – In patients with PE who are fully anticoagulated, we suggest

early ambulation rather than bedrest, when feasible (Grade 2C). Although, IVC filters
are not routinely used adjunctively in patients who are therapeutically anticoagulated,
they are used in rare circumstances by some experts (eg, those with poor
cardiorespiratory reserve), although this strategy is largely unproven. (See 'Adjunctive
therapies' above.)
● Prognosis – PE, left untreated, has a mortality of up to 30 percent, which is

significantly reduced with anticoagulation. The highest risk occurs within the first
seven days, with death most commonly due to shock. Prognostic models that
incorporate clinical findings (eg, Pulmonary Embolism Severity Index [PESI] and the
simplified PESI [sPESI] ( table 6)) and/or biochemical markers that indicate right
ventricle strain (natriuretic peptides, troponin) can predict early death and/or
recurrence. (See 'Prognosis' above.)
● Follow-up – Patients treated with unfractionated heparin and/or warfarin should be

monitored for laboratory evidence of therapeutic efficacy. Patients should also be
monitored for early (eg, recurrence) and late (eg, chronic thromboembolic pulmonary
hypertension) complications of PE, as well as for the complications of anticoagulation
and other definitive therapies. In addition, patients should be investigated for the
underlying cause of PE. (See 'Monitoring and follow-up' above.)
● Management of recurrence – Inadequate anticoagulation is the most common

reason for recurrent venous thromboembolism while on therapy. The clinician should
test for therapeutic levels of anticoagulants when relevant as well as considering
additional etiologies of recurrence (eg, suboptimal therapy, ongoing prothrombotic
stimuli, and alternate diagnoses). (See 'Management of recurrence on therapy' above.)
ACKNOWLEDGMENT
The UpToDate editorial staff acknowledges Victor F Tapson, MD, who contributed to earlier
versions of this topic review.
REFERENCES
1. Carson JL, Kelley MA, Duff A, et al. The clinical course of pulmonary embolism. N Engl J
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Med 1992; 326:1240.
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Treatment, Prognosis, and Follow Up of Acute Pulmonary Embolism

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Treatment, prognosis, and follow-up of acute pulmonary embolism in ad... https://www.uptodate.com/contents/treatment-prognosis-and-follow-up-...

Treatment, prognosis, and follow-up of acute

�������: Aaron S Weinberg, MD, MPhil, Parth Rali, MD

Literature review current through: Oct 2023.

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INITIAL APPROACH AND RESUSCITATION

Assess hemodynamic stability — The initial approach to patients with suspected PE

● Hemodynamically unstable PE (ie, high-risk or "massive" PE) is that which presents

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

Importantly, patients may become hemodynamically stable following resuscitation, or

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Hemodynamically stable — The majority of patients with PE are hemodynamically stable

● Peripheral intravenous access with or without intravenous fluids (see 'Hemodynamic

● Oxygen supplementation (see 'Respiratory support' below)

Hemodynamically unstable — A small percentage of patients with PE present with

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bedside echocardiography (transthoracic or transesophageal) to obtain a presumptive

The echocardiographic findings suggestive of PE and the diagnostic approach to

Pulmonary embolism response teams (PERT) — The decision to administer

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multidisciplinary approach to facilitate management of hemodynamically unstable patients

Respiratory support — Supplemental oxygen should be administered to target an

Hemodynamic support — The precise threshold that warrants hemodynamic support

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● Vasopressors – Intravenous vasopressors are administered when adequate perfusion

• Norepinephrine – Norepinephrine is the most frequently utilized agent in this

• Dobutamine – Dobutamine is sometimes used to increase myocardial contractility

Empiric anticoagulation — The administration of empiric anticoagulation depends upon

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One strategy is shown below:

• A high clinical suspicion for PE (eg, Wells score >6)

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patients with low-risk and intermediate-low risk PE ( algorithm 1A-B):

● For those who have contraindications to anticoagulation or have an unacceptably

It should be noted that when PE is proven and anticoagulation is contraindicated, an

● For most hemodynamically stable patients, we recommend against thrombolytic

Hemodynamically stable (ie, normotensive) patients with intermediate-risk/submassive PE

Indications and duration — Anticoagulant therapy is indicated for patients with PE

● Initial anticoagulation – Initial anticoagulant therapy is administered as soon as

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possible to quickly achieve therapeutic anticoagulation. A detailed discussion of agent

● Long-term anticoagulation (after discharge) – All patients are anticoagulated for a

● Indefinite anticoagulation – Select patients with PE are candidates for indefinite

Outpatient anticoagulation — In select patients with PE, outpatient therapy can be

● No requirement for supplemental oxygen

● No requirement for narcotics for pain control

● Normal pulse and blood pressure

● No recent history of bleeding or risk factors for bleeding ( table 3)

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● In another randomized trial of 114 patients with PE who were discharged on

Patients with subsegmental PE — The increasing use of computed tomography (CT)

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Our approach to anticoagulating patients with SSPE is the following:

The optimal duration of anticoagulation is unknown but similar to patients with

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details of which are discussed separately. (See "Venous thromboembolism: Initiation

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Hemodynamically unstable patients — In patients with PE who are hemodynamically

��: Aaron S Weinberg, MD, MPhil, Parth Rali, MD