Transcript Slide 1

PULMONARY EMBOLISM
Edward Hamaty D.O., FACCP, FACOI
Epidemiology
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Third most common acute cardiovascular disease
– After coronary ischemia and stroke
– Rate is 98 (nonfatal) and 107 (fatal) events per 100,000
persons in USA
– Over 300,000 hospitalizations and 50,000 deaths per
year
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Mortality increases with age and male sex
40% (idiopathic / primary PE's) have increased
incidence of developing overt cancer (9.1%-11.5%
will HAVE occult cancer at time of PE diagnosis)
10-20% of persons with PE have genetic
thrombophilic disorders
Patients with PE are at increased risk (>1.5X) of
death within 6 months of diagnosis
Predisposing Factors
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History of DVT, Concurrent DVT >95% of patients
with PE; PE occurs in >50% of cases with
phlebographically confirmed DVT [31]
Obesity ~40% (of cases) - risk is 1.7-3.2X versus
non-obesity (Primarily women with BMI ≥29 kg/m2)
Cancer ~30%
Heart Failure ~35%
Surgery - perioperative and up to 30 days post
surgery, ~20%
Fracture ~20%
Smoking (> 25 cigarettes/day)
Shock
Air Travel - particularly >3100 miles (5000 km) [51]
Predisposing Factors- con’t.
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Intake of (high doses of) Estrogen
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Especially in smokers, mainly on birth control
pills (oral contraceptives, OCP)
Third generation OCP have ~2X increased
risk of thromboembolism versus 2nd
generation
Estrogen replacement therapy (ERT):
increase risk ~1.2-2X in current users [6,8]
Factor V Leiden patients on OCPs may have
>30X increased risk of thromboembolism [30]
Trauma
Pregnancy: peri- and post-partum
Tumor Microembolization
Predisposing Factors- con’t.
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Hypercoagulable States
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Factor V Leiden - Resistance to Activated Protein C
(~12% of PE cases) [44]
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Factor II (Prothrombin) 20210A mutation - (~10% of PE
cases) [44] It was discovered in 1996 that a specific
change in the genetic code causes the body to produce
an excess of the prothrombin protein.
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Protein C, S or Antithrombin III Deficiency
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Acquired - antiphospholipid antibodies, paraneoplastic
syndromes
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Low levels of tissue factor pathway inhibitor (TFPI)
Elevated clotting factors and homocysteine likely contribute
Hypertension - at least in women [5]
Thrombosis of axillary subclavian vein (Paget-Shroetter
syndrome) [55]
Clotting Cascade
20210A mutation ↑ F II
F5L
RISK FACTORS FOR VENOUS
THROMBOEMBOLISM
THROMBOPHILIAS AND PE/DVT
THROMBOPHILIAS AND PE/DVT
High Risk for Fatal Outcome
Cancer
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~15% of underlying cancer if >1 independent episode of
PE
Low yield for finding occult malignancy if second event
is induced (for example, by surgery)
Congestive Heart Failure (CHF)
Chronic underlying lung disease
Recurrent PE
Elevated troponin (T or I) levels in setting of PE
was associated with an increased risk of shortterm mortality (OR 5.24, 95% CI 3.28-8.38) or
death due to PE (OR 9.44, 95% CI 4.14-21.49)
[32].
High Risk for Fatal Outcome
Pulmonary Hypertension (P-HTN) [55,64]
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Chronic recurrent PE with progression to P-HTN
Overall incidence of P-HTN ~4% within 2 years of initial
PE [64]
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Persistent right ventricular (RV) dysfunction after PE
increases risk for recurrent DVT by 2.4X [31]
BNP: An elevated brain natriuretic peptide (BNP) or Nterminal pro-brain natriuretic peptide (NT-proBNP) predicts
RV dysfunction and mortality [15,16]. This was illustrated by
two meta-analyses:
– A meta-analysis of 16 studies found that short-term mortality was
increased 6-fold among patients with a BNP >100 pg/mL and 16-fold
among patients with an NT-proBNP >600 ng/L [16].
– A meta-analysis of 13 studies (1132 patients) found that 30-day
mortality was increased among patients with an elevated BNP or NTproBNP (odds ratio 7.6, 95% CI 3.4-17) [17].
High Risk for Fatal Outcome
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BNP and NT-proBNP may predict other adverse outcomes.
– In an observational study of 73 consecutive patients diagnosed
with acute PE, serum BNP levels >90 pg/mL (drawn within four
hours of presentation) were associated with cardiopulmonary
resuscitation, mechanical ventilation, vasopressor therapy,
thrombolysis, and embolectomy, as well as death.
– Serum BNP levels <50 pg/mL identified 95 percent of patients
with a benign clinical course.
– Troponin T > 0.07 mcg/L plus NT-proBNP ≥ 600ng/L had higher
40 day mortality vs Trop T > 0.07 and NT-proBNP < 600 (33 vs
0 %)
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RV thrombus — Patients with PE and a right ventricular
(RV) thrombus have a higher 14-day mortality (21 versus 11
percent) and three-month mortality (29 versus 16 percent)
than patients without an RV thrombus.
Overall, few patients have recurrent emboli, particularly after
initiation of therapy
Pathogenesis
Clot forms at distal site, usually in distal veins in
the leg or in pelvic veins
Clots usually initiated by hypercoagulable state,
risk factors above, usually combination
Clots migrate to pulmonary vasculature
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Lodged thrombi release vasoconstrictors
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Most clots lodge in pulmonary arterioles or segmental
arteries
Lodging at pulmonary artery bifurcation leads to
"saddle" embolism
Serotonin
Thrombin
Endothelin
Others
Pathogenesis – con’t.
Release of these vasoconstrictors causes diffuse
pulmonary vascular constriction
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P-HTN follows
Severe, particularly acute, P-HTN can cause right heart
failure
In addition, can cause cardiac arrest (likely due to acute PHTN) [11,43]
Jugular venous distension on clinical exam has poor
sensitivity for severe P-HTN [55]
Alveolar Dead Space
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Vascular blockade (full or partial) leads to unperfused areas
of lung
These areas are called dead space (ventilated but not
perfused)
Alveolar dead space increases in PE in proportion to severity
of vascular blockade
Alveolar dead space can be estimated from difference of
exhaled and arterial CO2 levels
Pathogenesis – con’t.
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Loss of gas exchange surface also
occurs (reduced diffusion limit of carbon
monoxide)
Pulmonary Tumor Embolism [62]
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Presentation similar to more common
thromboembolic PE
Incidence ~15% amongst patients with solid
tumors
Breast, stomach, lung, liver cancers most
often reported
Consider in any patient with cancer who
presents with acute dyspnea
Pathology
Cardiac Consequences of Acute PE
Symptoms [13]
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Symptoms are non-specific, not very sensitive;
high suspicion must be maintained
Dyspnea 77% (A-a gradient)
Tachypnea 70%
Chest Pain 55% (usually pleuritic)
Tachycardia 43%
Cyanosis 18%
Hemoptysis 13%
Syncope 10%
Systemic embolism may occur in patients with LR shunts [1]
Pleuritic chest pain in absence of dyspnea is
common first presentation [10]
Sudden cardiac arrest with pulseless electrical
activity [43]
Symptoms – con’t.
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Cough 43%
Leg Swelling 33%
Leg Pain 30%
Palpitations 12%
Wheezing 10%
Angina-like pain 5%
Differential Diagnosis
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Myocardial Infarction [13]
Pneumonia
Pulmonary Edema / Congestive Heart
Failure
Asthma, COPD Exacerbation
Intrathoracic Cancer
Pericardial Tamponade
Pneumothorax
Rib Fracture
Musculoskeletal Pain, Costochondritis
Sarcoma of the pulmonary artery (rare) [41]
Dissecting Thoracic Aneurysm
Primary Pulmonary Hypertension
Anxiety / Panic Attack
PE Prediction Rules
"Evaluation for Pulmonary Embolism"
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Suspicion should be high if ANY risk
factors or symptoms/signs are present
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>70% of patients who die of PE are not
suspected of having it
Only ~35% of patients suspected of having
PE actually have it
Pre-test probability is very important for
making clinical (diagnostic) judgements
PE testing is less reliable in older persons
than in younger persons [42]
Age is a major risk factor, particularly with
underlying predisposing conditions
Clinical Probability Calculation [3,10]
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Risk factors are assigned points – Modified Well’s Score
Low (<2.0), Intermediate (2.0-6.0) High (>6.0) clinical
probability assigned
Clinical signs and symptoms of DVT: 3.0 points
Alternative diagnosis deemed less likely than PE: 3.0
points
Heart rate >100 beats per minute: 1.5 points
Immobilization or surgery in previous 4 weeks: 1.5
points
Previous DVT or PE: 1.5 points
Hemoptysis: 1.0 points
Cancer: 1.0 points
Clinical probabilities are used to determine evaluation
Clinical suspicion in experienced physicians likely as
good as quantitative evaluation [27]
More complex clinical prediction rules have been
created with similar accuracy as above
Wells Clinical Prediction Rule for PE
Evaluation Scheme Based on Clinical
Probability [10,63]
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Low clinical probability: high sensitivity D-dimer (level
<500µg/L) to rule out PE
Lower extremity venous ultrasound (US) to rule in DVT
Helical CT angiography or V/Q scanning can also be
used to rule out PE in low probability
Intermediate probability: CT angiography or V/Q
scanning
High clinical probability: CT angiography or V/Q
scanning
Helical CT scan may substitute for V/Q scan when
combined with lower extremity US [1]
Helical CT scan can be used safely as primary
diagnostic test to rule out PE [57,58]
Negative CT angiography results effectively rule out
PE as well as standard angiography []
Additional testing is done following results of initial test
Evaluation Scheme Based on
Clinical Probability [10,63]
V/Q Scans
VQ scan results correlated reasonably well with positive
pulmonary angiograms in PIOPED [15]
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Goal is to limit pulmonary angiography to a minimum number of
patients
Helical CT angiography is generally preferred over V/Q scanning
Computerized tomographic (CT) pulmonary angiography is as
effective as standard pulmonary angiography and safer for ruling out
PE [9]
Percentages are % of patients with positive pulmonary angiograms
in PIOPED Study [15]:
V/Q Scan
High PTP
Intermediate Low
High probability
95%
86%
56%
Intermediate
66%
28%
15%
Low probability
40%
15%
4%
Quantitative prediction tools recommended for initial pretest probability prediction [27]
V/Q Scan AND Clinical Probability
Specific Evaluation [32,42,63]
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Routine Laboratory Tests in Suspected
PE
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Electrolytes, complete blood count,
coagulation parameters (PT, aPTT)
ECG (standard) and ECG with right sided
leads on all patients
All patients should have an Arterial Blood Gas
(ABG, preferably on room air)
A PaO2 between 85 and 105 mmHg exists in
approximately 18 percent of patients with PE
Normal A-a gradient found in <6% of patients
with PE (see below)
High Sensitivity D-Dimer Test
Lower extremity venous US with doppler
measurements
ECG Changes
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Most common ECG is
normal sinus rhythm:
23% of submassive, 6%
of massive PE
Sinus Tachycardia
extremely common
Right Axis Deviation; S
in I, Q in III, inverted T in
III "classic changes" but
uncommon
If classic changes are
present, anticoagulation
should be started,
pursue evaluation
Right sided leads should
be evaluated
High Sensitivity D-Dimer [17,33]
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High negative predictive value for PE (based on pulmonary
angiography)
For D-dimer <500ng/mL, negative predictive value (NPV) 91-99% [36]
For D-dimer >500ng/mL, sens=93%, spec=25%, and positive predictive
value (PPV) = 30%
Test is also useful for DVT rule out (<500ng/mL): NPV 92%
For indeterminant V/Q scans, combination of D-Dimer and
ultrasonography gave a definitive diagnosis in 62% of patients (others
underwent angiography) [16]
SimpliRED bedside D-dimer test + alveolar dead space [ADS]
calculation can be used in place of V/Q scans to rule out PE [36,46]
Most patients with a normal ADF and a negative D-dimer do not have
PE (98 percent)
Use of D-dimer test alone to rule out PE may not appropriate [39,40,46]
D-Dimer testing has reduced specificity in older persons (~10%) versus
<40 years (67%) [42]
Patients with normal D-Dimer combined with low pretest clinical
probability of PE could be safely discharged without further evaluation
(NPV >99.5%) [33,49,50]
D-Dimer testing should be included in evaluation of PE in nearly all
ambulatory patients
D-Dimer less helpful for hospital inpatients (elevations common and
unrelated to PE)
Hi Sensitivity D-Dimer
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High negative predictive value for PE
(based on pulmonary angiography)
For D-dimer <500ng/mL, negative
predictive value (NPV) 91-99%
For D-dimer >500ng/mL, sens=93%,
spec=25%, and positive predictive value
(PPV) = 30%
PPV and NPV are affected by
prevalence.
Test is also useful for DVT rule out
(<500ng/mL): NPV 92%
If pretest probability is intermediate (27.8)
you are supposed to image, but if you
order a D-Dimer what do the results
mean?
Prevalence of 27.8% (Well’s Intermediate), Sensitivity of
93%, Specificity of 25%
Sensitivity
= 93%
Disease +ve
28
100
Disease -ve
26
80 people test
positive……….
of whom 26 have
the disease
Testing +ve
54
72
False
positive
rate = 75%
(1-Sp)
So, chance of
disease is 26/80
about 32.5%
(PPV quoted at
30%)
Incidence of PE in the General
Population
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650,000 to 900,000/year
Current US Population = 307,085,301
Incidence Ranges :
– From 650,000/307,085,301 = 0.0021 or
2/1000
– To 900,000/307,085,301 = 0.00293 or
3/1000
– Admittedly this includes newborns,
children, etc. but is being used for
illustrative purposes.
Prevalence of 0.003%, Sensitivity of 93%, Specificity of 25%
Sensitivity
= 93%
Disease +ve
3
1000
Disease -ve
3
751 people test
positive……….
of whom 3 have
the disease
Testing +ve
748
997
False
positive
rate = 75%
(1-Sp)
So, chance of
disease is with a
+ test is 3/751 or
about 0.4%
(The lower the
prevalence, the
more false
positives)
Sensitivity and specificity don’t vary
with prevalence
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Test performance can vary in different settings/
patient groups, etc.
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Occasionally attributed to differences in disease
prevalence, but more likely is due to differences in
diseased and non-diseased spectrums
D-Dimer
D-Dimer
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False Positive D-Dimer
– Pregnancy
– Trauma
– Postoperative Recovery
– Inflammation
– Cancer
– Rheumatoid Factor
– Older Age
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False Negative D-Dimer
– Heparin
D-Dimer
CXR
CXR
Atelectasis
Hampton’s Hump
Prominent PA
Westermark’s Sign
Ventilation-Perfusion (V/Q) Scans [15]
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High probability scans identify only ~50% of patients with PE
overall
Abnormal (high + intermediate + low prob) scans detect 98%
of PE's, but low specificity
About 60% of V/Q scans will be indeterminant (intermediate
+ low probability)
Of intermediate probability scans, ~33% occur with
angiographically proven PE
Test results not affected by presence of pre-existing cardiac
or pulmonary disease
Conclude: normal test rules out PE in ~98% of cases
Note that low probability test still has ~15-25% chance of PE
However, there were no deaths due to PE within 6 months in
a study of 536 patients with low probability scans [35]
Further evaluation is clearly required for intermediate
probability scans
For low probability scan with normal D-dimer level, no
additional workup needed
Consider helical CT in patients with non-diagnostic V/Q scan
[45]
NPV of helical CT with nondiagnostic V/Q is 96% [45]
Ventilation-Perfusion (V/Q) Scans
V/Q with Large Defect
V/Q with Multiple Defects
V/Q with Subsegmental Defects
Lower Extremity Doppler US [18,19,34]
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To evaluate for DVT as possible cause of PE
or to help rule in PE
Up to 40% of patients with DVT without PE
symptoms will HAVE a PE by angiography
Serial US should be probably be performed in
patients with abnormal (or non-diagnostic)
V/Q scans and positive D-Dimers [34]
These US should be carried out on days 1, 3,
7, and 14 [32]
A positive US on any of these days with
abnormal V/Q rules IN a PE [32]
Negative serial US scans reduce
likelihood of PE to <2% [20]
Venous Ultrasound
Normal Compression US
DVT Vein Resisting Compression
DVT Location of Vein Marked
Normal Color Doppler
Venous Ultrasound
A subtotal occlusive thrombus
in the right popliteal vein is
shown in this colour Doppler
image.
Right lower extremity (A) transverse
and (B) saggital images from color
Doppler ultrasound demonstrates
blood flow in the femoral artery but
not in the common femoral vein
(arrows). This is an indirect finding
that suggests common femoral
DVT.
Helical (Spiral) Computed Tomography
(CT) [22,37,48]
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Helical CT scanning produces volumetric twodimensional image of lung
This is accomplished by giving IV contrast
agent and rotating detector around the patient
Total acquisition time is <30 seconds
PE appears as a filling defect that may be
central, eccentric or mural
The embolism may completely or partially
occlude the vessel
Test is very quick, requires IV contrast and
careful interpretation and is costly
Helical (Spiral) Computed Tomography
(CT)
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Reported sensitivity 53-100% (83% in PIOPED II) ,
specificity 81-100%. (96% in PIOPED II) N Engl J
Med. 2006 Jun 1;354(22):2317-27.
PE rate with negative helical CT and lower extremity
ultrasound in patients with moderate or low clinical
probability PE is ~2%, high clinical probability PE ~5%
[57]
Thus, anticoagulation can be safely withheld in
moderate to low clinical probability patients with
negative helical CT and lower extremity ultrasound [57]
Combination of helical CT with lower-extremity
ultrasonography and V/Q scan may avoid invasive
angiography [48]
Helical CT alone can be used safely to rule out PE [58]
Helical CT appears to increase the diagnosis of PE
and reduce angiography [22]
Helical (Spiral) Computed
Tomography (CT)
CT – con’t.
Infarct
CT Pre and Post Lytic Therapy
A-a Gradient in Evaluation for PE [14]
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Normal A-a gradient may be seen in PE in ~6% of
patients with PE [1]
An arterial blood gas should be done to determine the
level of respiratory dysfunction. A PaO2 between 85
and 105 mmHg exists in approximately 18 percent of
patients with PE.
A-a gradient depends on age and body position
In supine position, Normal A-a Gradient ~ 103.50.42xAge
~2% of patients with normal A-a gradient, no history of
DVT/PE, had abnormal V/Q scan
Normal A-a gradient in patients with low pretest
probability makes PE very unlikely
Pulse oximetry >95% on room air at diagnosis
associated with low risk of serious morbidity [61]
A-a gradient is not currently a recommended part of
decision making in PE
Echocardiography [53]
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Transthoracic echocardiography is not sensitive as screening test
to rule out PE [47]
However, echocardiography is a very sensitive indicator of
massive or unstable PE
Echocardiography should be done on any patient with suspected
massive or unstable PE
Also critical for selecting patients for thrombolysis or other
aggressive therapy [4]
Right ventricular (RV) function is most predictive of outcomes
About 40% of patients with PE and normal blood pressure (BP)
have abnormalities of the RV
Unstable patients include those with RV hypokinesis, dilation,
abnormal septal motion, patent foramen ovale, free floating rightheart thrombus
Large PEs predicted by >30% loss of blood flow to either lung (on
V/Q Scanning)
Pulmonary artery pressures can be estimated (physical exam has
poor sensitivity) [56]
May be used for chronic monitoring of P-HTN as well [52]
Echocardiography
Echocardiography
RV greater than LV with septal shift
Echocardiography
Clot in RA
Clot in RV
Echocardiography
Echocardiography
Echocardiography
Echocardiography
Contrast Pulmonary Angiography
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This has been the gold standard for diagnosis but it is highly
invasive
The pulmonary catheter may also be used therapeutically
(angioplasty)
Angiography can be avoided in most patients by using other
tests above
Positive result is a filling defect or sharp cutoff in a pulmonary
artery branch
A negative angiogram with magnification excludes clinically
significant PE
Increased sensitivity is obtained with subselective dye
injection
May be morbid with worsening shortness of breath, artery
perforation, others
Spiral CT scanning can be used to detect proximal PEs
instead of angiography [1]
CT pulmonary angiography is safer than standard invasive
angiography and can be used to effectively rule out PE [9]
Contrast Pulmonary Angiography
Contrast Pulmonary Angiography
Contrast Pulmonary Angiography
Selective Angiography with Clot
Contrast Pulmonary AngiographyNormal
Contrast Pulmonary AngiographyAbnormal
Magnetic Resonance Angiography
(MRA) [21]
– Techniques for use of MRA for
diagnosing PE are evolving rapidly
– Estimated sensitivity ~80% (~100% for
larger emboli), specificity 95%
– Non-invasive with little morbidity
– Dynamic gadolinium enhancement is
used, allowing high quality images
– Strongly consider prior to standard
invasive pulmonary angiography
Magnetic Resonance Angiography
(MRA)
MRA
After
resolution
Consider Underlying Causes
– Inherited Clotting Abnormalities:
deficiency in Protein S, C, or ATIII
– Underlying malignancy - may alter
Factor Va activity
– Collagen Vascular Disease: antiphospholipid syndrome, systemic lupus
Treatment Overview
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Anti-Coagulation is Mainstay of Therapy
[7,29]
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Standard or low molecular weight (LMW)
heparin equal in efficacy, safety
Standard heparin bolus 5000U - 10,000U
(higher for large PE) then 1000-1500U / hour
LMW heparin is usually given as fixed or
weight-adjusted qd or bid dose
Unlike standard heparin, LMW heparin does
not require monitoring or adjustment in partial
thromboplastin time (PTT) [29]
Heparin is usually used as a bridge to
warfarin therapy
Anti-Coagulation - Heparin
Anti-Coagulation - Warfarin
Oral Direct Thrombin Inhibitors
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Ximelagatran, an
oral direct thrombin
inhibitor has shown
promising efficacy,
is well tolerated,
and at least as
effective as
warfarin, but it
does not require
coagulation
monitoring or dose
adjustment .
Thrombolytic Therapy
– Tissue plasminogen activator (TPA) or
streptokinase are usually used
– Usually given to patients with
echocardiographic evidence of right
heart strain / failure
– Alteplase beneficial when added to
heparin in stable PE patients with right
hear strain [54]
Embolectomy
– Surgical embolectomy (thrombectomy)
only in very selective cases
– Perioperative morality is 25-50%
– Massive pulmonary embolism where
thrombolysis contraindicated
– Chronic thromboembolic pulmonary
hypertension
Treatment Algorithm for Acute PE
IVC Filter Placement [60]
– Usually, "Bird's Nest Filter" is placed in
IVC
– Generally reserved for patients with
recurrent PE on anti-coagulation
– May also be used for patients in whom
anti-coagulation is contraindicated
– Can be used as adjunct in massive PE
where thrombolysis is not an option
– Generally these are an accepted
therapy and fairly safe to implant
IVC Filter Placement
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Indications — Insertion of an inferior vena cava (IVC) filter is
indicated for acute PE in the following settings [31]:
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Absolute contraindication to anticoagulation (eg, active
bleeding)
Recurrent PE despite adequate anticoagulant therapy
Complication of anticoagulation (eg, severe bleeding)
Hemodynamic or respiratory compromise that is severe
enough that another PE may be lethal
Patients who have undergone embolectomy (surgical or
catheter) frequently undergo IVC filter insertion.
In addition, IVC filters are being used for PE prophylaxis in
select groups of patients. While the evidence base for these
indications is less robust, it appears reasonable to
individualize such cases and consider this approach.
IVC Filter Placement
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Outcome — IVC filters decrease recurrent PE [34,35]. However, a reduction in
mortality has not been conclusively demonstrated. One study suggested that IVC filters
may decrease mortality in patients with persistent hypotension due to PE (ie, massive
PE), but this is uncertain because the patients who received IVC filters were younger
and the effect of age was not considered [32].
In one trial, 400 patients with proximal deep venous thrombosis (DVT) were randomly
assigned to receive anticoagulation alone or anticoagulation plus an IVC filter [34]. The
trial found:
Fewer patients in the IVC filter group suffered PE within twelve days (1 versus 5
percent).
Two years later, there was no difference in survival or symptomatic PE. However,
recurrent DVT was more common among patients who received an IVC filter (21
versus 12 percent).
Eight years later, there were fewer symptomatic PE in the IVC filter group (6 versus 15
percent). However, recurrent DVT was more common among patients who received an
IVC filter (36 versus 27 percent) [35].
This trial suggests that the benefit of decreased recurrent PE must be weighed against
the consequence of increased recurrent DVT when deciding whether an IVC filter
should be placed in a patient with acute PE.
IVC Filter Placement
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Complications — Complications of
IVC filters are rare but include [34,36]:
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Complications related to the insertion process (eg,
bleeding, venous thrombosis at the insertion site).
Filter misplacement.
Filter migration.
Filter erosion and perforation of the IVC wall.
IVC obstruction due to filter thrombosis.
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Danaparoid [23]
– A heparinoid obtained from pig
intestinal mucosa after removal of
heparin
– Combination of heparan sulfate (84%),
dermatan sulfate (12%), chondroitin
sulfate (4%)
– Major activity is selective inhibition of
Factor Xa through antithrombin III
– High dose (2000U sc bid) more
effective than heparin iv in DVT and PE
Chronic Therapy with Warfarin or
SC standard or LMW Heparin
–
–
–
–
–
–
–
•
Usually maintained for 3-6 months after PE to prevent
recurrence
6 month therapy has nearly half of the recurrences as 6
week therapy [24]
Prolonged anticoagulation reduced risk of recurrence
80% versus 3 months [59]
INR of 2-2.85 is recommended in most cases
Patients with underlying coagulopathy may require
longer term or lifelong therapy
Overall risk of recurrence is ~2.5% during the 6-month
period of therapy
Serious bleeding complications occurred in 3.3% of
patients
Chronic prolonged therapy is very effective in
eliminating risk of recurrent fatal PE [12,59]
Anti-Coagulation - Warfarin
Chronic Thromboembolic Pulmonary
Hypertension [52]
– Pulmonary thromboendarterectomy for
symptomatic disease
– Contraindication to surgery is severe
underlying chronic lung disease
•
If surgery deferred, close monitoring
for progression is required
Thrombolysis [4,25,54]
•
Indications
–
–
–
–
•
Hemodynamic instability
RV Dysfunction (by echocardiogram) - RV
Dilatation, abnormal septal motion [54]
Anatomically large PE - multiple segments on
V/Q Scan or Angiogram
Extensive DVT - controversial use (probably
decreases post-thrombotic syndrome)
Absolute Contraindications to
Thrombolysis
–
–
–
–
Active or recent internal bleeding
History Hemorrhagic Stroke
Intracranial Neoplasm
Recent cranial surgery or head trauma
Thrombolysis
Relative Contraindications
•
–
–
–
–
–
–
–
–
Major surgery (within 10 days)
Cardiopulmonary Resuscitation (CPR)
Invasive procedure with 10 days inaccessible to external compression
Pregnancy
Coagulopathy
Severe Hypertension, uncontrolled
CVA (non-hemorrhagic)
Pulmonary Angiography + TPA has14% risk of major bleed vs. 4% in TPA
alone [26]
Dosing
•
–
–
–
–
–
–
–
No dosage adjustments needed
Initial: SK 250,000U over 30 minutes; UK 2,000U/pound over 10 minutes
Then: SK 100,000U per hour x 24 hours; UK 2,000U/pound/hour x 12-24
hours
TPA given 100mg over 2 hours or 0.6mg/kg over 3 minutes [54]
After administering thrombolytics, start heparin (dose by following PTT)
Coumadin may be added on 2nd day of heparin, but overlap should continue
>4 days
Pregnant patients are given full dose sc heparin instead of coumadin
Thrombolysis
Benefits of Thrombolysis [4,25]
•
–
–
–
–
–
–
–
–
Emboli clear faster with thrombolytics than with
anticoagulation [18]
Reduce pulmonary artery pressure and improve
echocardiogram at 2 and 24 hours
Reduce risk of combined endpoint of death or
decompensation [54]
No differences in overall survival in most studies
Improves longer term RV function in some studies with
thrombolytics
Thrombolytics increase risk of severe hemorrhage
including intracranial bleeding
Rate of major hemorrhage with thrombolysis is low,
however (<10%) [31]
In patients with RV dysfunction but normal systemic
BP, major bleeding in 0% [54]
Thrombolysis
Primary Prevention of PE [1]
Heparins
•
–
–
–
–
•
•
•
Low-dose Heparin 5000U sc bid-tid was the standard
agent
LMW heparin appears to be more effective for
prophylaxis than standard heparin
Variety of low dose heparins and heparinoids have
been used
Enoxaparin or Dalteparin (sc qd)
Low dose (INR ~1.5X control) warfarin may also
be effective
Aspirin 160mg po qd may be added to other
agents and reduces DVT and PE incidence by
about 30% after major orthopedic surgery [38]
Compression stockings should be used in ALL
patients unless contraindicated
Primary Prevention of PE
•
Inferior Vena Cava (IVC) Filters [28]
–
–
–
–
•
Consider use for prophylaxis in patients at
high risk for PE
Majority of these patients have large,
proximal DVTs
IVC Filters appear to reduce early PEs (at12
days) by 80%
However, in 2 year followup, IVC filters
increased risk of PE by nearly 2-fold
Leg elevation (following surgery, stroke)
may also prevent DVT's
Primary Prevention of PE
Primary Prevention of PE
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