1. Pulmonary Embolism
Diagnosis and Risk stratification
Mostafa Elshazly, MD
Prof. of pulmonary critical care medicine
Head of PVRU
Kasr Alainy School Of Medicine
Cairo University
3. • Acute pulmonary embolism (PE) is a relatively common
disease with an annual rate of 1–2 per 1000 patients [1,
2].
• The clinical presentation of acute PE is nonspecific and
highly variable, ranging from incidentally diagnosed
asymptomatic thrombi to sudden death [3].
1 Naess IA et al. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 5: 692–9.
2 Silverstein MD, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population based study. Arch Intern Med
1998; 158: 585–93.
3 Stein PD et al. Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. Am J Med 2007; 120: 871–9.
4. • As a result, a clinical suspicion of PE is frequently raised,
whilst the diagnosis is only confirmed in 10–20% of
patients [1,2].
• Diagnostic algorithms have been developed to ensure
reliable and efficient management of patients with
clinically suspected PE
1 Douma RA et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. Ann
Intern Med 2011; 154: 709–18.
2 van Belle A et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and
computed tomography. JAMA 2006; 295: 172–9
5. • Pulmonary embolism (PE) is a relatively common acute
cardiovascular disorder with high early mortality rates
that, despite advances in diagnosis and treatment over
the past 30 years, have not changed significantly.
J Bĕlohlávek, V dytrych, a linhart. pulmonary embolism, part I. epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation,
diagnosis and nonthrombotic pulmonary embolism. exp clin cardiol 2013;18(2):129-138.
6. • Once acute PE is diagnosed, prompt initiation of anticoagulant
therapy is indicated to prevent thrombus extension and recurrent
(fatal) PE.
• However, the risk of such an adverse outcome is highly variable,
ranging from <1% to >15% .
1 Aujesky D et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005; 172: 1041–6.
7. • Management decisions including early discharge or prescription
of thrombolytic therapy should preferably be based on
reproducible risk stratification of the individual patient [1, 2].
1 Aujesky D et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005; 172: 1041–6.
2 Konstantinides SV et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35: 3033–80
8. • For the long-term treatment of acute PE, the decision to continue
or stop anticoagulant therapy, after an initial period of 3 months,
depends on the balance between the risk of recurrent venous
thromboembolism (VTE) and of anticoagulant-associated
haemorrhage.
9. Diagnostic Management Of
Clinically Suspected Acute PE
• Symptoms that may suggest the presence of acute PE are the
sudden onset of dyspnea, pleuritic chest pain, hemoptysis,
extremity swelling suggestive of deep vein thrombosis (DVT) and
syncope [3].
In large diagnostic management studies, the PE prevalence amongst
patients with a clinical suspicion of PE ranged from 10% to 30% .
10. Integrated approach
• The first step in the diagnostic management of patients with
clinically suspected acute PE is to determine whether the patient
has signs and symptoms of haemodynamic shock.
• If so, patients should be immediately referred for additional
imaging tests and thrombolytic therapy should be started without
waiting for a CDR result or D-dimer level.
12. • Pulmonary embolism (PE) is the third cause of mortality
by cardiovascular disease after coronary artery disease
and stroke.
• In Western countries, it remains one of the leading causes
of death in the puerperium and the postoperative period.
Cohen AT, et al; VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated
morbidity and mortality. Thromb Haemost 2007;98(4):756–764.
13. • The incidence of PE is estimated to be approximately 60 to 70
per 100,000, and that of venous thrombosis approximately 124
per 100,000 of the general population (1,2).
1. Oger E. Incidence of venous thromboembolism in a communitybased study in western France. Thromb Haemost 2000;83:657-60.
2. Widimský J, Malý J, Eliáš P, et al. Doporučení pro diagnostiku a léčbu akutní plicní embolie. Vnitř. Lék 2008; 54: 1S25-1S72
14. J Bĕlohlávek, V dytrych, a linhart. pulmonary embolism, part I. epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation,
diagnosis and nonthrombotic pulmonary embolism. exp clin cardiol 2013;18(2):129-138.
15. • Nonetheless, PE is difficult to diagnose because of
protean clinical manifestations and poor sensitivity and
specificity of symptoms and signs.
16. • Nonetheless, PE is difficult to diagnose because of
protean clinical manifestations and poor sensitivity and
specificity of symptoms and signs.
17. • However, it is still underdiagnosed and up to 80% of PE
found at autopsy have not been suspected ante mortem, a
proportion which has not decreased in the last 30 years.
Stein PD, henry JW. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest 1995; 108(4):978–981
18. • However, considerable progress has been made in the workup of
patients with clinically suspected PE, which is based on the
sequential use of pretest clinical probability, plasma D-dimer
measurement, and computed tomography pulmonary
angiography (CTPA).
20. • These different diagnostic tests have been used in rational
and cost-effective diagnostic strategies, and the
assessment of clinical probability has been shown to
improve patients’ outcomes.
Roy PM, Meyer G, Vielle B, et al; EMDEPU Study Group. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann
Intern Med 2006;144(3):157–164
22. • Assessment of PE pretest probability (low, intermediate, or high)
and hemodynamic status is essential to guide additional cost-
effective evaluation and may aid in the interpretation of
subsequent tests.
• Wells
• Geneva
24. Well’s Criteria
(Modified And Simplified)
• CHADS
1. Clinical features of DVT 2.Cancer
3. Heart rate > 100/min 4. Hemoptysis
5.Alternative diagnosis less likely
6.DVT/PE in past
7.Surgery in past 4 weeks or immobilization for 3 days
26. Pulmonary Embolism Rule-out Criteria
PERC
• Pulmonary embolism can be ruled out clinically if none of the 8
PERC criteria are present in a patient with a low pretest
probability of PE (e.G. Wells PE CPG score of <3) that is
consistent with the ‘gestalt‘ of an experienced physician
27. Pulmonary Embolism Rule-out Criteria
PERC
1. Age < 50 years 2. Pulse < 100 beats min
3. Sao2 >or= 95% 4. No hemoptysis
5. No estrogen use
6. No surgery/trauma requiring hospitalization within 4 weeks
7. No prior venous thromboembolism (VTE)
8. No unilateral leg swelling
29. Pulmonary Embolism Rule-out Criteria
PERC
• HAD CLOTS
1. Hormone 2. Age >50 3. DVT/PE history
4. Coughing blood 5.Leg swelling 6. O2 < 95%
7. Tachycardia 100+ 8. Surgery/trauma <28 days
30. Pulmonary Embolism Rule-out Criteria
PERC
• What should you do if a patient has a positive d-dimer test, but
on reflection the investigation was not indicated — for example,
the patient meets the PERC rule criteria, which is consistent
with a senior clinician’s ‘gestalt’, but a d-dimer test has already
been performed?
31. Pulmonary Embolism Rule-out Criteria
PERC
• Ignore the result with respect to assessing VTE risk (go back and
use the Wells criteria for PE!).
• Consider the other possible causes of an elevated D-dimer and
manage as indicated (this may include no further action).
34. Plasma D-dimers
• Plasma D-dimers are the end product of plasmin-mediated fibrin
degradation.
• Plasma D-dimer levels are elevated in the presence of an acute
blood clot because activation of the coagulation system is
associated with simultaneous fibrinolysis activation.
35. Plasma D-dimers
• Although D-dimers are fibrin specific, fibrin specificity for VTE
is not high because fibrin is also produced under several other
circumstances such as malignancies, inflammation, infection,
necrosis or aortic dissection.
36. Plasma D-dimers
• Although D-dimers are fibrin specific, fibrin specificity for VTE is not
high because fibrin is also produced under several other
circumstances such as malignancies, inflammation, infection,
necrosis or aortic dissection.
• D-dimer specificity is also limited in elderly patients, pregnant women
and hospitalized individuals.
37. Plasma D-dimers
• A multicenter, prospective management study evaluated age-adjusted
(age X 10 μg/l, above 50 years) cutoff levels in a cohort of 3,346
patients with suspected PE.
• Using the age-adjusted (instead of the standard 500 mg/l) D-dimer
cutoff increased the number of patients in whom PE could be excluded
from 6.4% to 30% in patients aged 75 years or older, without a
significant increase in the rate of VTE events during follow-up
Righini M, Van Es J, den Exter PL, et al. Ageadjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA 2014;311:1117–24
38. Factors that can or the accuracy of the d-dimer
assay in diagnosing PE
39. Factors that can or the accuracy of the d-dimer
assay in diagnosing PE
• False-positive d-dimer
• Cancer and malignancy , Recent surgery , Infection (eg, pneumonia, sepsis)
• Pregnancy , Age > 70 years , Disseminated intravascular coagulation
• Trauma , Arterial thrombosis , Acute coronary syndrome/MI
41. CTPA
• In recent years, spiral CTA has become the gold standard for
assessing patients with suspected PE , particularly as a tool
capable of confirming or excluding the presence of thrombi in the
pulmonary bed.
• Advanced multidetector systems require only a short exposure
(approximately 10 s) with the patient holding their breath.
Torbicki A, Perrier A, Konstantidines S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2008;29:2276-315
42. CTPA
• Contra-indications:
• Renal failure
• Pregnancy
• Allergy to radio-contrast
Torbicki A, Perrier A, Konstantidines S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2008;29:2276-315
43. Echocardiography
• Echocardiography, which should be available at all hours in any
intensive care unit, is currently considered – in addition to physical
examination – the main adjunct method of examination in acute PE.
• Echocardiography offers a potential for emergency risk stratification
based on evaluation of the hemodynamic impact of the disease on the
right-heart chambers while also allowing for comprehensive non-
invasive assessment of the patient’s hemodynamic status
44. Echocardiography
• Echocardiography, which should be available at all hours in any
intensive care unit, is currently considered – in addition to
physical examination – the main adjunct method of examination
in acute PE.
47. Low-risk PE describes normotensive
patients diagnosed with acute
symptomatic PE that have a low
risk for short-term complications
(all-cause mortality, recurrent VTE,
and major bleeding)
48. Low-risk PE describes normotensive
patients diagnosed with acute
symptomatic PE that have a low
risk for short-term complications
(all-cause mortality, recurrent VTE,
and major bleeding)
Intermediate–high-risk PE describes
confirmed PE, hemodynamic stability,
and a risk of PE-related complications
similar to patients with high-risk PE.
N
M
N
N
50. Markers of myocardial injury and overload
• Troponin - released from right ventricle Injury
• Cardiac BNP - released from cardiac myocytes in response to elevated pressures RVD
*A normal troponin and BNP can safely exclude high risk patients with a negative
predictive value of 97-100%
• H-FABP (heart type fatty acid binding protein) – early marker for injury
(good for prognosis as well)
• NGAL (neutrophil gelatinase associated lipocalin) & Cystatin C – both indicating
kidney injury, also shown to have prognostic value
55. • Pulmonary embolism (PE) remains a major contributor to global
disease burden.
• Risk-adapted treatment and follow-up contributes to a favorable
outcome.
• Age-adjusted cutoff levels increase D-dimer specificity and may
decrease overuse of imaging procedures and overdiagnosis of PE.
58. Treatment Of Acute PE
• Patients with acute PE should be stratified according to the short-
term PE-related mortality risk.
• Risk stratification starts with identifying patients in
haemodynamic shock, who are classified as having high-risk or
massive PE with an estimated 30-day PE-related mortality risk of
>15%
Risk stratification of acute PE
61. Treatment Of Acute PE
Risk stratification of acute PE
• The Hestia decision rule consists of a set of criteria that can be
used to select patients with low-risk PE who are candidates for
early discharge or outpatient treatment.
63. Treatment Of Acute PE
Risk stratification of acute PE
Management Of High-risk Patients
• Thrombolytic therapy is generally recommended for high-risk
patients with PE with overt Haemodynamic instability without a
high risk of Bleeding complications
64. Treatment Of Acute PE
Risk stratification of acute PE
Management Of High-risk Patients
• Percutaneous catheter-directed therapy and surgical
embolectomy are alternatives to thrombolytic therapy, for
example in the case of a contraindication to thrombolysis or
after thrombolytic therapy has failed or is deemed inadequate as
first-line treatment
65. Treatment Of Acute PE
Risk stratification of acute PE
Management Of NonHigh-risk Patients
• Amongst the nonhigh-risk hemodynamically stable patients, two
key questions with regard to therapeutic management remain to
be answered
(i) Do patients with intermediate-risk PE benefit from thrombolytic
therapy?
(ii) Which patients with low risk of adverse outcome are suitable
candidates for outpatient treatment or early discharge?
66. Treatment Of Acute PE
Risk stratification of acute PE
Management Of NonHigh-risk Patients
Do patients with intermediate-risk PE benefit from
thrombolytic therapy?
Thrombolytic therapy in hemodynamically stable intermediate-risk patients
with PE reduces the risk of the composite endpoint consisting of
haemodynamic deterioration and death at the cost of an increase in the
incidence of major haemorrhage.
67. Treatment Of Acute PE
Risk stratification of acute PE
Management Of NonHigh-risk Patients
Do patients with intermediate-risk PE benefit from
thrombolytic therapy?
thrombolytic therapy cannot be recommended for
haemodynamically stable intermediate-risk patients with
PE.
68. Treatment Of Acute PE
Risk stratification of acute PE
Management Of NonHigh-risk Patients
Do patients with intermediate-risk PE benefit from
thrombolytic therapy?
These patients should receive standard anticoagulant
therapy and close monitoring, whilst thrombolytic therapy
should be reserved for patients with haemodynamic
deterioration during the first days of treatment.
69. Treatment Of Acute PE
Risk stratification of acute PE
Management Of NonHigh-risk Patients
(i) Which patients with low risk of adverse outcome are suitable
candidates for outpatient treatment or early discharge?
In conclusion, it has been shown that outpatient treatment of
patients with PE based on the Hestia decision rule or a
combination of several exclusion criteria and the PESI score is
safe.
70. Treatment Of Acute PE
Risk stratification of acute PE
Management Of NonHigh-risk Patients
(i) Which patients with low risk of adverse outcome are suitable
candidates for outpatient treatment or early discharge?
The combination of a clinical prediction rule, laboratory
biomarkers and/or findings on imaging tests to further optimize
the identification of patients who can be safely managed in the
outpatient setting remains to be evaluated.
71. Treatment Of Acute PE
Risk stratification of acute PE
Initial anticoagulant therapy (first 3 months)
Acute PE requires initial treatment with a direct onset
anticoagulant drug to prevent the extension of thrombosis or
fatal recurrent VTE
72. Treatment Of Acute PE
Risk stratification of acute PE
Initial anticoagulant therapy (first 3 months)
➢Weight-adjusted subcutaneous LMWH is the treatment of choice
for the large majority of patients.
➢IVUH is reserved for patients with
➢Severe renal impairment (creatinine clearance <20–30 mL min1),
➢ Patients with a high risk of haemorrhage including those receiving
thrombolytic therapy, haemodynamically unstable patients and
➢Individuals who are extremely overweight or underweight.
73. Treatment Of Acute PE
Risk stratification of acute PE
Long-term anticoagulant therapy (after the first 3 months)
74. Treatment Of Acute PE
Risk stratification of acute PE
Long-term anticoagulant therapy (after the first 3 months)
To determine the optimal duration of treatment after the initial 3
months, the perceived risk of anticoagulant therapy-associated
haemorrhage should be weighed against the risk of recurrent
VTE in every patient individually
75. Treatment Of Acute PE
Risk stratification of acute PE
Long-term anticoagulant therapy (after the first 3 months)
To determine the optimal duration of treatment after the initial 3
months, the perceived risk of anticoagulant therapy-associated
haemorrhage should be weighed against the risk of recurrent
VTE in every patient individually
82. Inferior Vena Cava Filters
• Insertion of a temporary or permanent inferior vena cava filter is
another intervention that has been recently studied to assess its
effect on mortality from pulmonary emboli, with preliminarily
favorable results.
83. Inferior Vena Cava Filters
opatients with contraindications to anticoagulation,
othose who have complications from the use of anticoagulation,
o those who fail to attain adequate anticoagulation while
undergoing treatment.
84. Symptomatic Subsegmental Pulmonary Embolism
To Treat Or Not
• The use of CTPA is associated with an increase in the incidence
of previously undiagnosed SSPE.
• The clinical relevance of such findings is debated and indirect
evidence suggests that some SSPE might not require
anticoagulant treatment.
85. Symptomatic Subsegmental Pulmonary Embolism
To Treat Or Not
• In a statement from the Fleischner Society on the management of
suspected acute PE, it is suggested that the clinical relevance of small
peripheral PE and the need to give anticoagulant treatment in such
patients are a matter to debate [28].
• It was also suggested that in patients with small PE and no DVT, the
risks associated with anticoagulant treatment might outweigh the
benefits.
86. Symptomatic Subsegmental Pulmonary Embolism
To Treat Or Not
• In the meantime, we would suggest:
1) To perform a CTPA only when necessary, i.e. in patients with a
high clinical probability or a positive D-dimer test.
2) If a SSPE is seen on the CTPA, the result should be reviewed with
an expert thoracic radiologist.
87. Symptomatic Subsegmental Pulmonary Embolism
To Treat Or Not
• In the meantime, we would suggest:
3) In case of SSPE, a bilateral compression US should be performed
and anticoagulant therapy should be given in case of DVT.
4) In the absence of DVT, the decision to treat or not to treat SSPE
should be individualized, taking into account the bleeding risk and
the patients' values and preferences.