Author: Dr Taylor Thomson Harvard Medical School 2008-07-22
What is a pulmonary embolism?
Pulmonary Embolism (PULL-mun-ary; EM-bo-lizm) is a condition caused by a blood clot that has suddenly blocked one or more of the arteries of the lung. Health care professionals often refer to pulmonary embolism by its initials, PE. It is a serious medical condition that afflicts over 100,000 people in the United States each year. Almost a third of patients with pulmonary embolism die, usually within two hours of the blood clots arrival in the lung. If the condition is diagnosed and anticoagulant therapy (also known as “blood thinner”) is given promptly, the prognosis dramatically improves. Mortality from properly treated PE is around 3%.
To understand how PE can cause such problems, it is helpful to review some basic physiology. Normally,
the right side of the heart receives blood from the large veins of the
body and pumps it through the lung arteries to the microscopic lung
capillaries where oxygen is absorbed and carbon dioxide is removed as we
breathe. The oxygen-rich blood then leaves the lung,
enters the left side of the heart, and is pumped into arteries leading
to various parts of our bodies. The pressure in our arteries is called
our “blood pressure.” After delivering oxygen and picking up carbon dioxide, blood returns to the heart through veins of increasing size.
PE
begin as very small blood clots in the veins of the legs, usually where
two smaller veins join to form a larger vein. The clots slowly enlarge
as the platelets and the clotting proteins in blood attach to the
original clot. This may cause pain or swelling in the
involved leg, a problem called Deep Vein Thrombosis (or DVT). If the
clot breaks free from the wall of the vein it is carried by the flow of
blood through the major vein in the abdomen, the inferior vena cava. The
clot then travels through the chambers of the right heart and enters
the pulmonary arteries, which get smaller and smaller, like the branches
of a tree. Usually the clot breaks free from the vein on more than one occasion, or it breaks apart as it travels. We know this because patients often have more than one artery blocked with clot at the time PE is recognized. The clots commonly lodge in the arteries in the lower lungs. Usually,
some clot is left behind in the leg, which may grow and break free
causing a second, or multiple episodes of pulmonary embolism.
What are the symptoms?
When
blood clots arrive in the lung they can cause death by blocking most of
the blood flow through the lungs and thus into the left heart, causing a
catastrophic drop in blood pressure, leading to shock and death. Somewhat smaller blood clots may cause sudden shortness of breath or a sense of impending doom. Chest pain beneath the breastbone (sternum) may occur. Fainting or light-headedness may result from low blood pressure. Even smaller clots lodge in pulmonary arteries near the edge of the lung may cause chest pain under the ribs. This pain is sharp, or knife-like, and usually worsens with deep breathing. Finally, pulmonary emboli may damage the lung, leading to bleeding. When this happens, patients may cough up blood.
Curiously, some PE do not cause any symptoms, or symptoms that are so subtle that they do not cause alarm. Sometimes
shortness of breath or chest pain is thought to be from other
conditions, such as a heart or asthma attack, pneumonia, or a bruised
rib. Thus, detecting (or diagnosing) PE can be a major challenge for health care professionals. The major clue
to the presence of a PE is the sudden appearance of shortness of breath
or chest pain, especially when the person has painful swelling in the
leg or has a risk factor for developing blood clots (see below).
Major Symptoms of Pulmonary Embolism
- Shortness of Breath
- Chest pain beneath the breastbone or under the ribs that worsens with deep breathing
- Near fainting and sweating (the sign of a potentially large pulmonary embolism)
- Coughing up blood (called hemoptysis)
- Rapid heart rate
What causes pulmonary embolism?
Because nearly all PE arise from DVT, the risk factors for the two conditions are nearly identical. Some
individuals are predisposed to forming clots in their veins and thus
place them at risk for PE. This may run in families and be due to
genetic differences in clotting factors. A lack of
anticlotting factors, such as antithrombin, protein C, or protein S, are
frequently found in patients who develop pulmonary emboli before age
50. Other clotting factors, such as factor V Leiden or a mutation in the
prothrombin gene may cause pulmonary embolism at any age, although
usually not until after adolescence. Some patients without a family
history of pulmonary embolism or DVT may acquire disorders of clotting
as they grow older. Polycythemia Vera and the development of antibodies to phospholipid (antiphospholipid antibody syndrome) are two examples.
Other
clots form after major surgery when the blood flow may be sluggish from
bed rest or the effect of anesthesia, which relaxes veins. Surgical
procedures with the highest risk of DVT and PE include hip and knee
replacements, neurosurgery, operations near veins, and any surgery that
requires a long time in the operating room. Hip or leg fractures also increase risk. Accordingly, anticoagulants are often given to prevent clots following high-risk surgeries or accidents (see Prevention, below).
A number of medical conditions and medications that may cause pulmonary embolism are listed below:
Medical Conditions and Medications that may Cause Pulmonary Embolis
- Cancer (which may trigger clotting factors, making it more likely to form clots)
- Smoking
- Heart failure
- Previous DVT or PE (increases the chance for a another, even years later)
- Kidney problems, such as nephrotic syndrome
- Birth control pills
- Estrogen replacement therapy
- Tamoxifen
- Obesity
- Pregnancy
Obviously, many individuals have these conditions or take these medications and never develop DVT or PE. Risk becomes greater when two or more of these risk factors exist, such as smoking if you are obese or pregnant.
A significant number or patients with PE have no identifiable risk factor. The
pulmonary emboli appear to have come out of the blue. This is probably
due to an inherited abnormality of blood clotting that scientists have
yet to identify.
How is pulmonary embolism diagnosed?
If
symptoms suggest pulmonary embolism, laboratory testing is needed.
Because of the serious consequences of untreated PE, most clinicians
advise starting treatment with anticoagulation during the testing
process, recognizing that testing may not find pulmonary emboli or
reveal another diagnosis that does not require anticoagulation. This
better-safe-that-sorry approach balances the risk of a few hours of
anticoagulation during testing with the risk of a second, possibly fatal
pulmonary embolism.
Testing starts with an electrocardiogram and chest x-ray. These tests cannot detect pulmonary emboli. They
are simple, readily available tests that may determine if a heart
attack or pneumonia is causing the symptoms suggesting PE. If
these or explanations can be found for shortness of breath or chest
pain then PE is very unlikely, especially in patients without risk
factors.
In patients with signs of PE who also
have a painful swollen leg, leg vein ultrasound testing would logically
be the next test performed if it could be done quickly. Leg vein ultrasound may reveal the remaining clot in the leg and confirm the need for anticoagulation. Leg
vein ultrasound bounces sound waves through the skin into the leg and
can detect veins and the blood flow through them (using the Doppler
principle). The ultrasound probe is pressed gently over a vein. It the vein has a clot in it, it will not collapse under pressure and the flow is reduced. Since the treatment for DVT and PE is similar, some clinicians may advise no further testing at this point.
The most commonly used test for finding pulmonary emboli is a special
type of CT scan, called computed tomographic pulmonary angiography
(CTPA). The adjacent picture shows a patients being helped
into the circular CT scan at the Massachusetts General Hospital in
Boston. Once comfortably in position, a sterile iodine containing
liquid (the contrast) is injected into a vein in the arm and the patient
takes a deep breath and is asked to hold it. This can be a challenge if
you are not feeling well but is important to avoid blurry results.
The
contrast can be “seen” by CTPA as it fills the pulmonary arteries.
Pulmonary emboli are detected when the liquid fails to fill the entire
artery, leaving voids that represent clots. A
CTPA image from a young man with a PE in the left branch of the
pulmonary artery (PA) is shown. This image was taken just above the
heart where the PA and the aorta (AO) exit. The contrast has entered
the PA making it bright white. A void in the left PA (arrow) and
another void in a branch of the PA leading toward the sternum (arrow)
indicate the presence of a large PE.
The CT scaner can also be
moved down to the legs where it may also "see" clots in the veins as the
contrast in pumped into the circulation and through the circulation of
the legs. This part of the test is called CT venography.
CTPA is
very reliable for detecting large clots and has the benefit of imaging
all of the structures in the chest. Because many patients suspected of
having pulmonary emboli do not, in fact, have them this is a great
advantage. Conditions that mimic pulmonary emboli that can be detected
by CTPA include pneumonia, lung cancer, or a leaking aorta (termed
aortic dissection). If aortic dissection is suspected, anticoagulation prior to testing is not begun, as it could prove fatal. This underscores the complexity of the diagnostic approach to PE, and the need for clinical judgment.
The CTPA has difficulty “seeing” smaller clots. It sometimes misses them altogether, or “sees” clots when they do not exist. We
know this because the CTPA has been compared to the “gold standard” for
diagnosis, pulmonary angiography, a form of heart catheterization
described below. These failures of CTPA are due to
technical limitations of the technique and due to variation in the
expertise of the radiologist interpreting the images captured by the
CTPA. For example, when we compare the interpretations of
different radiologist looking at the same images they sometimes come to
different conclusions. Accordingly, some specialists ask for a second radiologist to look at CTPA images if the images are difficult to interpret. If uncertainty remains, additional testing may be required to confirm or exclude the presence of smaller clots.
One such test is the D-dimer blood test. D-dimers almost always appear in the blood when clots form in the legs and travel to the lungs. Thus the absence
of D-dimers (a negative test) makes DVT or PE very unlikely, especially
if other tests for DVT and PE are negative and clinicians suspect
another diagnosis. In fact, if clinicians consider PE unlikely and
another explanation for chest pain or shortness of breath is found, a
negative D-dimer test may be sufficient to exclude the diagnosis of PE
or DVT.
Cardiac ultrasound, which uses sound waves to image the
heart, may rarely reveal a blood clot caught in the chambers of the
right heart. Cardiac ultrasound also detects if a large blood clot has placed a strain on the right heart.
Another test is the ventilation perfusion lung scan. This test detects voids in blood flow in the lung. If the scan is normal (no voids in lung blood flow) then pulmonary emboli are not the problem. If the scan shows big voids and the clinician strongly suspects PE, then the presence of clots is confirmed. This is an older test that has been largely replaced by CTPA.
In some instances, the results of one or more of the above tests are ambiguous or conflicting. In such cases, pulmonary angiography is needed to confirm or exclude pulmonary. This test involves placing a catheter through the veins and chambers of the right heart directly into the pulmonary arteries. It is a form of cardiac catheterization and is done in larger hospitals and specialized centers. In some cases, it is worth the travel, expense, and modest risk to know for sure.
In summary, the diagnosis of PE often involves a series of tests that depend on the clinical circumstances. Leg ultrasound makes sense as the first test in patients with leg symptoms. For
patients seen in the office or emergency department, D-dimer testing
may be the next recommended test, especially if PE is considered less
likely. Starting with these two tests may avoid the xray
exposure and higher cost of the CTPA. For patients with risk factors
for PE whose breathlessness or chest pain is unexplained, treatment for
PE should be considered while the CTPA is urgently scheduled.
What if my doctor is unsure if I have a pulmonary embolism?
It
is important to confirm the diagnosis of PE with certainty. A missed
diagnosis can lead to a second episode of PE than might be fatal. An
erroneous diagnosis of PE results in months of unnecessary treatment.
The combination of D-dimer testing, clinical judgment, and the CTPA make the diagnosis in the majority of cases. However,
if tests give conflicting results, or if the findings are at odds with
clinical judgment, it is time for a second opinion. Smaller
blood clots detected with CTPA when D-dimer testing and leg ultrasound
are normal, or if the clinical suspicion of PE is low, should raise
suspicion about the diagnosis. A second radiologist should
examine the CTPA images and either a ventilation perfusion lung scan or
pulmonary angiography should be considered. The
consequences of a false positive diagnosis are months of unnecessary
anticoagulation and the risk of bleeding (see below under treatment).
How is a pulmonary embolism treated?
Anticoagulation prevents the clot in the lung and any remaining clot in the leg from growing in size. This greatly reduces the chance of a second pulmonary embolism developing, which is the primary goal of anticoagulation. Unfractionated
heparin, given intravenously, or low molecular weight heparin, given by
injection under the skin (subcutaneously), are the standard approaches. Recent
studies suggest that low molecular weight heparin provides better
protection at lower cost for most patients with medium to smaller
clots.
Heparin or low molecular weight heparin is usually
continued for 5-7 days while another medication in pill form, called
warfarin (Coumadin®), is started. Low molecular weight heparin can be
injected into the skin by the patient, a family member, or a visiting
nurse at home. Warfarin takes at least 5 days to adequately lower
clotting factors to protect from the development of new clots. The proper dose is determined by a blood test (usually an International Normalized Ratio or INR). When this ratio is consistently 2-3, the heparin is discontinued.
Types of Low Molecular Weight Heparins
- Enoxaparin (Lovenox®)
- Dalteparin (Fragmin®)
- Tinzaparin (Innohep®)
Warfarin
is recommended for a minimum of 3 months in patients with a reversible
risk factor, such as surgery or leg fracture, and for 6-12 months for
patients with a pulmonary embolism that has occurred for no apparent
reason. Indefinite treatment is recommended for patients
with 2 or more episodes of DVT or PE, and is considered for some
patients with inherited disorders of clotting factors.
Thrombolytic
therapy (also called “clot busters”) may also be recommended under
special circumstances. Unlike heparin, which stops the clotting process
and allows for the bodies own, slower thrombolytic mechanisms to
dissolve the clot over days to weeks, intravenous thrombolytic therapy
markedly accelerate this process. They improve right heart
function, lung blood flow, and may improve exercise performance months
later in comparison to anticoagulation alone. However, thrombolytic
drugs increase risk of serious bleeding, including brain hemorrhage. Thus,
clinicians reserve the use of thrombolytic therapy for patients with
major complications from pulmonary emboli, such as shock, or for
patients at risk of dying.
Determining risk is difficult. Blood
tests of heart strain or heart injury, such as Brain Natriuretic
Peptide (BNP) and troponin, may indicate that the right ventricle is on
the edge of failing. Cardiac ultrasound may confirm this. However,
no large clinical trial has determined that these tests accurately
identify an immediately life threatening situation sufficient to justify
the increased risk of thrombolytic therapy. If you find
yourself in this situation, you will need to weigh the potential
benefits of improved survival and perhaps better exercise tolerance
months later against the possibility of a stroke. In my
experience, younger patients with very large PEs and low blood pressure
who are at low risk for stroke often choose thrombolytics. Older patients at higher risk for bleeding often opt to ride it out with anticoagulation. Thrombolytic therapy works best when given shortly after a prompt diagnosis.
A
metal filter can be placed intravenously into the inferior vena cava
where it traps blood clots before they reach the lung. This device is
recommended in patients with PE who cannot use anticoagulants because of
bleeding complications or contraindications to full doses of
anticoagulation, such as recent surgery. A filter is also recommended for patients who develop another pulmonary embolism while taking anticoagulant therapy.
For
patients with massive pulmonary emboli who cannot receive thrombolytic
therapy but are critically ill from their PE, surgical removal of the
clot (surgical embolectomy) may be needed. This requires heart bypass during clot removal. Some catheter devices are capable of removing or breaking up large clots (called catheter embolectomy or fragmentation).
What precautions may I or my doctor take to prevent pulmonary embolism?
As
noted, patients undergoing high-risk surgical procedures are given
anticoagulants at lower doses or are offered inflatable compression
boots for both legs. Both methods help to prevent the development of DVT and pulmonary emboli after surgery. Examples
of high risk situations are surgery in patients over the age of 60, or
surgery in younger patients with cancer or prior PE. For very high-risk surgeries, such as total hip or knee replacement or surgery for major trauma, both approaches are used. For
low risk situations, defined as minor surgery in patients less than 40
years of age without additional risk factors, early physical activity,
if possible, is recommended.
It is not clear if air travel increases the risk of DVT or PE. Walking
every 2 hours, doing deep knee bends, and avoiding dehydration are
reasonable strategies for preventing DVT on long international flights.
Where can I get more information about pulmonary embolism on the Web?
The National Institutes of Health
The Journal of the American Medical Association (JAMA) Patient Page
Medline Plus
VascularWeb : Society for Vascular Surgery
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