A Common disorder and potentially
650,000 cases occurring annually
Highest incidence in hospitalized
Autopsy reports suggest it is commonly
Presentation is often “atypical”
Signs and symptoms are frequently
vague and nonspecific and rarely
Untreated mortality rate of 20% 30%, plummets to 5% with timely
4. So What Do We Do ???
Do we under diagnose/over
6. Venous Thromboembolism
“ The detachment of larger or smaller fragments from the
end of the softening thrombus are carried along by the
current of blood and driven in remote vessels. This
gives rise to the very frequent process upon which I
have bestowed the name EMBOLIA.”
7. Risk Factors
Postpartum status (<4wk)
Genetic mutations (Factor V Leiden, Protein C & S deficiency, Prothrombin
mutations, anti-thrombin III deficiency)
Bedrest > 24 hr
Recent cast or external fixator
Long-distance travel or prolong automobile travel
Recent surgery requiring endotracheal intubation
Recent trauma (especially the lower extremities and pelvis)
8. Clinical Presentation
1)SIZE 0f clot and pre-existing cardiopulmonary
2) COMMON s/s of P.E are not specific to it
The Classic Triad: (Hemoptysis, Dyspnea, Pleuritic Pain)
Not very common!
Occurs in less than 20% of patients with documented PE
10. Clinical Features
Signs with Angiographically Proven PE
Tachypnea > 20/min
Fever > 37.8
S3 or S4 gallop
Lower extremity edema
11. IMPORTANT DEFINITIONS
VTE which occurred in the presence of
an antecedent (within 3 months) and transient major clinical risk
factor for VTE (for example surgery, trauma, significant immobility
and pregnancy or puerperium). The GDG also considered VTE that
occurred in association with hormonal therapy (oral contraceptive or
hormone replacement therapy) to be provoked as it
DVT or PE in a patient with no antecedent
major clinical risk factor for VTE who is not having hormonal therapy
(oral contraceptive or hormone replacement therapy). Patients with
active cancer, thrombophilia or a family history of VTE should also be
considered as having an unprovoked episode because these
underlying risks will remain unchanged in the patient
12. Who do we work up?
- Pretest Probability
Definition: “The probability of the target disorder (PE)
before a diagnostic test result is known”.
Used to decide how to proceed with diagnostic testing
and final disposition
This is really what it boils down to!
13. WELL’S CRITERIA FOR P.E
signs and symptoms of DVT (minimum of leg swelling and
pain with palpation of the deep veins)
alternative diagnosis is less likely than PE
rate greater than 100 beats per minute
(for more than 3 days) or surgery in the previous four weeks 1.5
(on treatment, treated in the last 6 months, or palliative)
probability simplified score
PE likely More than 4 points
PE unlikely 4 points or less
15. Diagnostic Testing
Chest X-Ray Myth:
“You have to do a chest x-ray so you can
find Hampton’s hump or a Westermark
Most chest x-rays in patients with PE are
nonspecific and insensitive
16. Chest X-ray Eponyms of PE
A dilation of the pulmonary vessels
proximal to the embolism along with
collapse of distal vessels, sometimes with
a sharp cutoff.
A triangular or rounded pleural-based
infiltrate with the apex toward the hilum,
usually located adjacent to the hilum.
18. Diagnostic Testing
Most Common Findings:
Tachycardia or nonspecific ST/T-wave changes
Acute cor pulmonale or right strain patterns
Tall peaked P-waves in lead II (P pulmonale)
Right axis deviation
S1-Q3-T3 (occurs in only 20% of PE patients)
19. Diagnostic Testing
- Pulse Oximetry
The Pulse Oximetry Myth:
“ You must do a pulse oximetry reading, since
patients with pulmonary embolism are
Most patients with a PE have a normal pulse
oximetry, and most patients with an abnormal
pulse oximetry will not have a PE.
20. Diagnostic Testing
The ABG/ A-a Gradient myth:
“You must do an arterial blood gas and calculate
the alveolar-arterial gradient. Normal A-a
gradient virtually rules out PE”.
The A-a gradient is a better measure of gas
exchange than the pO2, but it is nonspecific and
insensitive in ruling out PE.
21. Diagnostic Testing
in every patient with a documented
maybe helpful in demonstrating right heart strain
fibrinolysis can reduce mortality by 50%!
22. Ancillary Test
Poor sensitivity and nonspecific
be as high as 20,000 in some patients
PTE does not alter count but if extreme,
consider polycythemia, a known risk factor
Don’t get one, terrible test in regard to
any predictive value
23. D-dimer Test
Fibrin split product
Circulating half-life of 4-6 hours
Quantitative test have 80-85% sensitivity, and 93-100% negative
Advanced age > 80 years
Post-partum < 1 week
Surgery within 1 week
Collagen Vascular Diseases
25. Ventilation/Perfusion Scan
- “V/Q Scan”
common modality to image the lung
And its use still stems from the PIOPED study.
noninvasive and sadly most often
many centers remains the initial test of choice
27. Spiral (Helical) Chest CT
Noninvasive and Rapid
Risk to patients with borderline renal function
Hard to detect subsegmental pulmonary emboli
29. Patient with signs or
symptoms of PE
Other causes excluded by assessment of general medical history, physical examination and chest X-ray
Two-level PE Wells score
PE likely (> 4 points)
PE unlikely (≤ 4 points)
Is CTPA* suitable** and available immediately?
Offer CTPA(or V/QSPECT or planar scan)
Contd.. On next slide
Immediate interim parenteral anticoagulant therapy
Was CTPA (or V/Q SPECT or planar scan) positive?
CTPA (or V/Q SPECT or planar scan)
Is deep vein thrombosis suspected?
Consider a proximal leg vein ultrasound scan
Advise the patient it is not likely they have PE. Discuss
with them the signs and symptoms of PE, and when and
where to seek further medical help. Take into
consideration alternative diagnoses
Diagnose PE and treat
PE unlikely (≤ 4 points)
Was the D-dimer test positive?
Is CTPA* suitable** and available immediately?
Immediate interim parenteral
Offer CTPA (or V/Q SPECT or planar
CTPA (or V/Q SPECT or planar scan)
Was the CTPA (or V/Q SPECT or planar scan) positive?
Diagnose PE and treat
Advise the patient it is not likely
they have PE. Discuss with them
the signs and symptoms of PE,
and when and where to seek
further medical help. Take into
consideration alternative diagnosis
32. PATIENT EDUCATION
Give patients having anticoagulation treatment verbal and written
how to use anticoagulants
duration of anticoagulation treatment
possible side effects of anticoagulant treatment and what to do if these
the effects of other medications, foods and alcohol on oral
monitoring their anticoagulant treatment
how anticoagulants may affect their dental treatment
taking anticoagulants if they are planning pregnancy or become
how anticoagulants may affect activities such as sports and travel when
and how to seek medical help.
immediate thrombin inhibition, which prevents
not dissolve existing clot
not work in patients with antithrombin III def.
In this case use hirudins
35. Offer a choice of low molecular weight heparin (LMWH) or fondaparinux to
patients with confirmed proximal DVT or PE, taking into account comorbidities,
contraindications and drug costs, with the following exceptions:
For patients with severe renal impairment or established renal failure
(estimated glomerular filtration rate [eGFR] < 30 ml/min/1.73 m2) offer
unfractionated heparin (UFH) with dose adjustments based on the APTT
(activated partial thromboplastin time) or LMWH with dose adjustments based
on an anti-Xa assay.
For patients with an increased risk of bleeding consider UFH.
For patients with PE and haemodynamic instability, offer UFH and consider
the LMWH, fondaparinux or UFH as soon as possible and continue it for at
least 5 days or until the international normalised ratio (INR) (adjusted by [VKA];
is 2 or above for at least 24 hours, whichever is longer.
Offer LMWH to patients with active cancer and confirmed
proximal DVT or PE, and continue the LMWH for 6 months
At 6 months, assess the risks and benefits of continuing
For patients with an increased risk of bleeding consider
with the action of Vit-K dependent factors: II, VII, IX,
and X, as well as protein C & S
temporary hypercoagulable state in first 5 days of
Important a patient is anticoagulated with heparin before initiating
INR is 2.0 – 3.0
Offer a VKA to patients with confirmed proximal DVT or
PE within 24 hours of diagnosis and continue the VKA for 3
months. At 3 months, assess the risks and benefits of
continuing VKA treatment
Offer a VKA beyond 3 months to patients with an
unprovoked PE taking into account the patient’s risk of
VTE recurrence and whether they are at increased risk of
bleeding. Discuss with the patient the benefits and risks
of extending their VKA treatment.
Syncope with persistent hemodynamic compromise
+/- patient with acute right heart strain
Altivase regimen is 100mg as a continuous IV
Prefibrinolytic therapy this was only therapy for massive
Carries a 40% operative mortality
Alternative is Transvenous Catheter Embolectomy
Consider catheter-directed thrombolytic therapy for
symptomatic iliofemoral DVT who have:
symptoms of less than 14 days’ duration and
good functional status and
a life expectancy of 1 year or more and
a low risk of bleeding.
41. VENA CAVAL FILTERS
Offer temporary inferior vena caval filters to patients with
proximal DVT or PE who cannot have anticoagulation
treatment, and remove the inferior vena caval filter when the
patient becomes eligible for anticoagulation treatment.
Consider inferior vena caval filters for patients with recurrent
proximal DVT or PE despite adequate anticoagulation
treatment only after considering alternative treatments such
increasing target INR to 3-4 for long-term high-intensity oral
anticoagulant therapy or switching treatment to LMWH.
Ensure that a strategy for removing the inferior vena caval
filter at the earliest possible opportunity is planned and
documented when the filter is placed, and that the strategy is
42. THROMBOPHILIA TESTING
Consider testing for hereditary thrombophilia in patients who
have had unprovoked DVT or PE and who have a first-degree
relative who has had DVT or PE if it is planned to stop
Do not offer thrombophilia testing to patients who have had
provoked DVT or PE.
Do not routinely offer thrombophilia testing to first-degree
relatives of people with a history of DVT or PE and
Consider testing for antiphospholipid antibodies in patients
who have had unprovoked DVT or PE if it is planned to stop
43. TAKEAWAY MESSAGE
Pulmonary Emboli remain a potentially deadly and common
event which may present in various ways
Don't be fooled if your patient lacks the “classic” signs and
Consider PE in any patient with an unexplainable cause of
dyspnea, pleuritic chest pain, or findings of tachycardia, tachpnea,
D-Dimers have NPV of 93-99%
Heparin remains the mainstay of therapy with the initiation of
Warfarin to follow
Pulmonary embolism is the most serious complication of venous thrombosis
It is the third most common cause of death in the US
As many as 60% of deaths in hospitalized patients are found to have pulmonary emboli
So, generally speaking it is a hard diagnosis to make….
As clinicians we must consider the diagnosis in patients to put us on the right path
PE It has a wide spectrum of patient presentation, which leads us to do suboptimal testing. This can stand in the way of a timely diagnosis
It’s important, because prompt diagnosis and treatment can dramatically reduce the mortality rate and morbidity of this disease.
Unfortunately, the diagnosis is missed far more than it is made. I want to offer you a historical perspective of the disorder
Do we under diagnose or over diagnose?
If we over diagnose, is it such a big deal? It’s just a few month of inconvenience of heparin and warfarin.
Aside from the potential morbidity of the anticoagulants,there are other problems.
The diagnoses carries a stigma which will contaminate all future medical encounters. Women may be barred from oral contraceptives, future pregnancies will be considered high risk. Elective surgery may be denied.
So, really after all these years, we are still left in the dark. We still don’t have a collective conscience on a standard approach to this problem.
Before we can answer any questions we have to understand the condition and this take us to virchow.
Everyone I’m sure is familiar with Virchow’s triad. It was first described by this German pathologist.
If we think of risk factors, we should think of them as the embodiment of the triad: hypercoagulability, stasis, and vessel injury.
So, essentially, under normal conditions, microthrombi are continually formed and lysed with the venous circulatory system.
When any one of the “risk states” exists, potential microthrombi may escape the normal fibrinolytic system and grow and propagate.
Pulmonary Emboli occurs when fragments of thrombus break loose and are carried through the right side of the heart into the pulmonary arterial tree.
Cancers of primarily adenocarcinoma and CNS tumors most often cause thrombosis.
We need to make special mention about patients with a prior history of DVT or PE.
Studies have revealed these patients have between a 5 to 30 times increased risk of a new DVT in response to a triggering event compared to those who have not had prior episodes.
All the above symptoms are a manifestation of cardiopulmonary stress caused by the cloth in the lung.
These produce symptoms perceived by the patient and the signs observed by you!
There are three common clinical presentations that you should be aware of:
1. Patient’s with pulmonary infarction may have pleuritic chest pain and can be hard to distinguish between that patient with infection pneumonitis
2. Submassive embolism are the hardest of all. By definition, they have an angiographically defined blockage of flow to an area served by less than two lobar arteries.
These patients have acute or unexplained dyspnea with exertion or at rest. So, they can be easily confused with infection, asthma, CHF and the like.
3. Finally, Massive PE, or a clot which obstructs two lobar arteries, so-called “Saddle Embolus”. These patients have acute cor pulmonaly often with syncope. You might think there having an MI or look septic!
These are the common symptoms that are associated with PE
As we mentioned in the previous slide, dyspnea and chest pain are not always preset.
The explanation is that with a small V/Q mismatch, the adaptive physiology of the pulmonary vasculature and bronchi produce intermittent shortness of breath. Because of this, we are easily distracted and looking for a cardiogenic cause of the dyspnea.
What about pleuritic chest pain, still not a home run!
In fact, up to 25% of patients ultimately diagnosed with a PE, never had any chest pain!
This is what makes the diagnosis so difficult!
Lets look a t a couple of these:
Myth #2 We are all taught this is a key component of the diagnosis. Right?
In fact, actually not having tachycardia is more commonly seen in patients who are found to have a PE!
What about fever? If a patient has a fever, it must not be a PE, right?
Although not common, Among patients with PE and no other source of fever, fever was present in one study in 43 of 311 patients (14%).
This could represent the likelihood that a specific patient , say a middle-aged man, with a specific past history, say hypertension and tobacco smoking who presents with a specific symptom complex: Chest pain, Dsypnea, or Diaphoresis has a specific diagnosis.
Because PE can present with or with any of the “classic signs and symptoms” and even the risk factors which contribute to PE are varied in frequency, we are left with a intuition at best!
As you can see there are a variety of test that we use to arrive at a diagnosis.
Some better than others!
So, lets talk about these individually.
Granted that most are abnormal, but certainly not diagnostic.
It is true that in the original PIOPED study it was recommended but the main value is to exclude diagnoses the mimic PE and to aid in the interpretation of the V/Q scan
Here we see the dilated vessels and oligemia of westermark’s sign
And below Hampton’s Hump
A brief mention about the classic S1-Q3-T3, its appearance on the EKG may suggest PE, but study after study has shown it has no predictive value what so ever!
But you got to know it because question writers for the boards love it!
Actually, it is opposite of what you might think!
As with most dogma, we are taken back by what we thought was truth.
About 15% of patients with proven pulmonary embolism have a pO2 of 85mmHg or higher!
In one study, researches drew from there data various combinations of the PaO2 of 80mm Hg or more, the PaCO2 of 35mmHg or higher, and the A-a gradient of 20 mmHg or less.
They found that PE could not be excluded in more than 30% of patients with no prior cardiopulmonary disease.
Moreover, PE could not be excluded in more than 14% of patients with prior cardiopulmonary disease.
Conclusion, Blood gas levels are poor discriminate value to permit the exclusion of PE.
Diagnosing of early right ventricular strain is important because it is a strong predictor of subsequent death
Important to recommend echocardiogram with your admitting internist if a pattern of right heart strain is suggested by EKG.
Studies have documented that lives are saved with early fibrinolysis is considered in these patients.
Well, what is it?
Basically, the assay is enzyme-linked monoclonal antibody test used to identify the protein, D-Dimer.
D-Dimer itself is a unique degradation product that is produced by a plasmin mediated breakdown of cross-linked fibrin
Good test with respect to its negative predictive value.
The drawbacks are some of the false positives that we commonly see in the ER.
Qualitative RBC agglutination assay, low sensitivity and specificity and not good enough to comfortably rule out PE.
Quantitative, which measure the accurately the amount using a spectrophotometer.
Our lab uses the 2nd generation VIDAS d-dimer with a negative predictive value of 99.3%!
Essentially, a patient is injected with a radioisotope that travels through the pulmonary microcirculation and are detected by a gamma camera over the patient
A normal Perfusion study will have evenly distributed blood flow.
Then a patient inhales a radioactive gas and it is viewed as it washes over the bronchopulmonary tree.
A mismatch, areas of blocked perfusion and normal ventilation is interpreted by the radiologist and given reading as normal (never), high probability, or non-diagnostic/low-probability
The reason the low probability or non diagnostic scan category is so suspect is because in the PIOPED study this group had terrible inter-reader reliability. So, just beware.
The entire lung can be scanned while the patient holds there breath.
CT most useful benefit is in providing evidence for an alternative diagnosis or excluding it entirely.
The clinical significance for subsegmental PE are not well
known, but may be a marker for a larger PE
Given that the majority of V/Q studies are non-diagnostic, I prefer the CT as the initial test of choice in place of V/Q scan.
Right now there is no better test on the horizon of the immediate present to virtually rule out or in PE.
So what are our goals???
Heparin is the most frequently used drug in the treatment of PE.
Because heparin works by activating antithrombin III, this genetic mutation makes heparin ineffective.
FDA approved dose for Unfractionated heparin is 80units/kg IV bolus, then 18 units/kg/hr infusion to maintain the INR at 2.5-3
Lovenox is dosed at 1mg/kg every 12 hours or 1.5 mg/kg per day.
LMWH in pregnancy only preferred for convenience sake.
This is because the anticoagulants protein C and S have short half-lives compared with the procoagulant vitamin K-dependent proteins.
So, this gives rise to the clinical importance that heparin must be continued for at least five days after beginning Coumadin
The incidence of progressive thrombosis and embolization is 40% when starting warfarin directly, compared to only 8% when beginning after a patient has been anticoagulated with heparin.
Treatment is usually for 6 months, but may continue lifelong
For critically ill patients, a very rapid infusion of 100mg over 10 minutes is preferred.
Alternative is Retavase, you can give it as two IV doses of 10 units, each over two minutes.
This is a procedure where a suction tip catheter is placed in contact with the thrombus under fluoroscopy and sucked out while catheter is withdrawn