Pulmonary Embolism (PE)
Pulmonary embolism is usually caused by a blood clot, although other substances can also form emboli and block an artery.
Symptoms of pulmonary embolism vary but usually include shortness of breath.
Doctors often diagnose pulmonary embolism by looking for blockage of a pulmonary artery using computed tomography (CT) angiography or lung scanning.
Anticoagulant drugs (sometimes called blood thinners) can be given to people at high risk to prevent pulmonary embolism.
Anticoagulant drugs are used to thin the blood and keep emboli from enlarging while the body dissolves the clots; other measures (such as drugs to break up blood clots or surgery) may be needed for people who appear to be at risk of dying.
The pulmonary arteries carry blood from the heart to the lungs. The blood picks up oxygen from the lungs and travels back to the heart. From the heart, the blood is pumped to the rest of the body to provide oxygen to the tissues. When a pulmonary artery is blocked by an embolus, people may not be able to get sufficient oxygen into the blood. Large emboli (massive, or high-risk pulmonary emboli) cause so much blockage that the heart cannot pump enough blood through the pulmonary arteries that remain open, and the blood pressure decreases. If too little blood is pumped or the heart is strained excessively, the person can go into shock and die. Sometimes, the blockage of blood flow causes pulmonary infarction, which can cause severe pain but is reversible.
The body usually breaks up small clots more quickly than larger clots, keeping damage to a minimum. Large clots take much longer to disintegrate. For unknown reasons, in a small percentage of people, the clots do not break up and form scars, which may cause more permanent symptoms.
Pulmonary embolism affects about 350,000 people per year and causes 85,000 deaths per year in the United States. It affects mainly adults.
The most common type of pulmonary embolism is a
Usually the blood clot forms in a leg or pelvic vein when blood flow slows down or stops, as may occur in the leg veins when a person stays in one position for a long time after an injury (for example, a hip fracture), major surgery, or prolonged sitting during travel. Other causes include conditions that make the blood more likely to clot or the presence of a foreign substance within the bloodstream (for example, an intravenous catheter).
The cause of blood clots in the veins may not be discernible, but many times predisposing conditions (risk factors) are obvious. These conditions include
Advanced age, particularly older than 60 years
Blood clotting disorder (increased risk of clotting, called a hypercoagulable state)
Catheters inserted into a large vein for giving drugs or nutrients (indwelling venous catheters)
Reduced mobility (for example, after surgery or an illness or during a long car ride or air travel)
Injury to the pelvis, hip, or a leg
A kidney disorder called nephrotic syndrome
Major surgery within the past 3 months
Disorders of the bone marrow that make the blood too thick
Pregnancy or the period after delivery
Prior blood clot
Use of estrogens, for example, as treatment for menopausal symptoms or as contraception (in which case the risk is particularly high among women who are older than 35 or who smoke)
Use of estrogen receptor modulators (such as raloxifene or tamoxifen)
Use of testosterone replacement therapy
People who sit for long time periods without moving around (as may happen during air travel) are at slightly increased risk.
Far less often, blood clots form in the veins of the arms. Occasionally, clots are found in the right side of the heart, while traveling to the lungs. Once a clot breaks free into the bloodstream, it usually travels to the lungs.
The sudden blocking of an artery of the lung is not only caused by blood clots. Other material can also form emboli.
Fat can escape into the blood from the bone marrow when a long bone is fractured or during bone surgery and form an embolus. Sometimes fat can also escape during procedures such as liposuction and fat grafting.
Amniotic fluid that is forced into the pelvic veins during a complicated childbirth can form an embolus.
Cancer cells in clumps may break free into the circulation to form tumor emboli.
Air bubbles may form emboli if a catheter in one of the large veins (central veins) is inadvertently opened to air. Air emboli may also form when a vein is operated on (such as when a blood clot is being removed). An additional risk is underwater diving (decompression sickness).
Infected material may also form emboli and travel to the lung. Causes include intravenous drug use, certain heart valve infections, and inflammation of a vein with blood clot formation and infection (septic thrombophlebitis).
A foreign substance can be introduced into the bloodstream, usually by intravenous injection of inorganic substances such as talc or mercury by injection drug users, where it can form emboli and travel to the lung.
Cement may occasionally enter the bloodstream after a procedure called vertebroplasty.
Pulmonary embolism symptoms depend on the extent that the pulmonary artery is blocked and on the person’s overall health. For example, people who have another disease, such as chronic obstructive pulmonary disease or coronary artery disease, may have more disabling symptoms.
Small emboli may not cause any symptoms, but when symptoms do occur, they often develop abruptly.
Symptoms of pulmonary embolism may include
Shortness of breath may be the only symptom, especially if pulmonary infarction does not develop. Often, the breathing is very rapid, and the person may feel anxious or restless and appear to have an anxiety attack.
Some people have pain in the chest. The heartbeat may become rapid, irregular, or both.
In some people, particularly those with very large emboli, the first pulmonary embolism symptoms are light-headedness or loss of consciousness. If people suddenly lose consciousness, their body may shake, appearing to be seizures. Blood pressure may drop dangerously low (a condition called shock), the skin may be cool and have a blue color (cyanosis), and the person could suddenly die.
In older people, the first symptom of pulmonary embolism may be confusion or deterioration of mental function. These symptoms usually result from a sudden decrease in the heart’s ability to deliver enough oxygen-rich blood to the brain and other organs.
Pulmonary infarction is when some of the lung tissue does not receive enough blood flow and oxygen and appears on imaging studies to die due to blockage of a lung blood vessel by a pulmonary embolus. Usually the embolus causing pulmonary infarction is small. The symptoms of pulmonary infarction develop over hours. If pulmonary infarction occurs, the person may cough with blood-stained sputum, sharp chest pain when breathing in, and in some cases fever. Symptoms of infarction often last several days but usually become milder every day.
In those rare people whose emboli persist partly or completely, the blood pressure in the lungs' blood vessels can increase. This increase in blood pressure can cause symptoms, such as shortness of breath, swelling of the ankles or legs, and weakness, which tend to develop progressively over, months, or years.
Doctors suspect pulmonary embolism based on the person’s symptoms and risk factors, such as recent surgery, a prolonged period of bed rest, or a tendency to form blood clots. A large pulmonary embolism may be relatively easy for doctors to diagnose, especially when the person has obvious conditions that could cause pulmonary embolism, such as signs of a blood clot in a leg. However, in many cases, symptoms are minimal or are confused with symptoms of other disorders such as pneumonia, a heart attack, asthma, or even kidney stones, which is an important reason why pulmonary embolism is often difficult to diagnose. Indeed, pulmonary embolism is one of the most difficult serious disorders for doctors to recognize and diagnose.
Some routine tests can provide clues that a pulmonary embolism has occurred. However, these tests cannot diagnose with certainty whether a pulmonary embolism is truly present.
A chest x-ray may reveal subtle changes in the blood vessel patterns that occur after embolism and may reveal signs of pulmonary infarction. However, the x‑ray results are often normal, and even when they are abnormal, they rarely enable doctors to establish the diagnosis with certainty.
Electrocardiography (ECG) may show abnormalities. These abnormalities can support or suggest the diagnosis of pulmonary embolism but cannot confirm it.
The level of oxygen in the blood is measured with a sensor that is attached to a fingertip (oximetry). Because pulmonary embolism blocks pulmonary arteries, the level of oxygen in the blood may be low. Sometimes doctors also take a sample of blood and measure the level of oxygen and other gases in it.
Doctors first judge how likely pulmonary embolism seems to be, based on information such as the person's risk for pulmonary embolism, the severity of their symptoms, and the results of early tests (such as the chest x-ray and level of oxygen in the blood). Importantly, obvious risk factors may be completely absent.
If pulmonary embolism seems unlikely, a blood test that measures a substance called d‑dimer is typically done. This test may be the only test needed in such people. If in these people the d-dimer level is normal, then the probability that a pulmonary embolus has occurred is extremely low. However, although a low level of D-dimer in such people means that pulmonary embolism is unlikely, a high level does not necessarily mean that pulmonary embolism is likely. Other disorders, such as infection or injury, can cause the d-dimer level to be high so additional testing is needed to confirm the diagnosis.
If pulmonary embolism seems more likely or if the result of the d-dimer test is abnormal, other testing is done, usually one or more of the following:
CT angiography is a type of CT scan. It is fast, noninvasive, and fairly accurate, particularly for large clots. In this test, contrast material is injected into a vein. The contrast material travels to the lungs, and a CT scanner generates images of blood in the arteries to determine if a pulmonary embolism is blocking blood flow. CT angiography is the imaging test most often used to diagnose pulmonary embolism. The size of the heart may also indicate how much the heart is being strained.
A lung ventilation perfusion scan is noninvasive and fairly accurate but takes longer than a CT scan. A tiny amount of radioactive substance is injected into a vein and travels to the lungs, where it outlines the blood supply (perfusion) of the lung. Completely normal scan results usually indicate that the person does not have a significant blood vessel obstruction. Abnormal scan results support the possibility of pulmonary embolism but may also indicate the possibility of other disorders, such as emphysema, which can result in decreased blood flow to areas where lung tissue has been damaged.
Usually, the perfusion scan is done with a lung ventilation scan. In this test, the person inhales a harmless gas containing a trace amount of radioactive material, which is distributed throughout the small air sacs of the lungs (alveoli). The areas where carbon dioxide is being released and oxygen is taken up can then be seen on a scanner. By comparing this scan to the pattern of blood supply shown on the perfusion scan, doctors can usually determine whether a person has had a pulmonary embolism. Doctors sometimes use a lung perfusion scan if a person has a kidney problem that prevents the use of CT angiography because the contrast material used for the CT might further damage the kidneys.
Ultrasonography of the legs is noninvasive and can identify clots in the legs, which are the usual sources of pulmonary embolism. The absence of clots on this test does not rule out pulmonary embolism. However, if ultrasonography reveals blood clots, and the lung symptoms are minimal, people are occasionally treated as they would be for pulmonary embolism without any further testing, because the treatment for both conditions is often the same.
Pulmonary artery angiography is very rarely needed to diagnose pulmonary embolism.
Echocardiography may show that a blood clot is in the right atrium or right ventricle of the heart. the results of this test may help doctors determine the severity of the embolism by showing that the right side of the heart is strained by trying to push blood through the clots.
In people who have no apparent risk factors for blood clots or recurring clots, doctors may also measure proteins in the blood to determine whether a clotting disorder is the cause.
The likelihood of dying from pulmonary embolism is very low, but massive pulmonary embolism can cause sudden death. Most deaths occur before the diagnosis is suspected, often within a few hours of the embolism occurring. Factors important in affecting the prognosis include
Factors that help determine the prognosis include indicators of how the body responds, such as the blood pressure, heart rate, oxygen level, and whether drugs are required to help raise the blood pressure.
Anyone with a serious heart or lung problem is at greater risk of dying due to a pulmonary embolism. A person with normal heart and lung function usually survives unless the embolus blocks half or more of the pulmonary arteries.
Given the danger of pulmonary embolism and the limitations of treatment, doctors try to prevent blood clots from forming in the veins of people at risk. In general, people, particularly those who are prone to clotting, should try to be active and move around as much as possible. For example, when traveling on an airplane for a long period, people should try to get up and move around every 2 hours.
Doctors select the anticoagulants, physical prevention measures, or combination of measures depending on the reason the person is at risk of pulmonary embolism and the person's underlying health status.
For certain people, an anticoagulant drug (also called a blood thinner) is given, most often heparin.
Heparin comes in two forms:
Traditional and low molecular weight heparins appear equally effective. Heparin is the most widely used drug for reducing the likelihood of clots forming in calf veins after any type of major surgery, especially surgery on the legs. Small doses are injected just under the skin, usually within 6 to 12 hours after surgery, and ideally additional doses are given until the person is up and walking again.
Hospitalized people at high risk of developing pulmonary embolism (such as those with heart failure, immobility, or obesity, or who have had clots in the past) benefit from small doses of heparin even if they are not undergoing surgery. Low-dose heparin does not increase the frequency of severe bleeding complications, but heparin can increase minor oozing of blood from wounds.
Warfarin, an anticoagulant given by mouth, is used much less commonly now because when warfarin is used, people need regular blood tests to monitor the effect of warfarin, warfarin interacts with many drugs that people may be taking, and newer drugs are safer and more effective. Low-molecular-weight heparin is more predictable than the standard form of heparin and is commonly used for prevention of clots in people undergoing surgery that has a high risk of causing clots, such as hip or knee replacement.
Newer direct oral anticoagulants include those such as fondaparinux, rivaroxaban, apixaban, edoxaban, and dabigatran that inhibit the formation of substances that enhance the body’s production of clots. These drugs are effective in prevention and in general are safer than warfarin. Nonetheless, warfarin is still considered the best choice for some people such as those with metallic heart valves.
For people who have undergone surgery—especially older people—the risk of clot formation can be reduced by
Intermittent air compression devices can provide rhythmic external pressure to keep blood moving in the legs. However, these devices alone are inadequate to prevent clot formation in people who have undergone certain high risk surgeries such as hip or knee replacement surgery.
Elastic compression stockings provide steady pressure on the blood vessels of the legs to keep blood flowing. They are likely less effective than intermittent compression devices, but still may be helpful in reducing the risk of blood clots in the legs.
In patients who are at high risk of developing pulmonary embolism and who cannot take anticoagulants due to a high risk of bleeding, a filter (called an inferior vena cava filter) may be placed inside a large vein between the heart and the inferior vena cava, which returns blood to the heart from the lower part of the body. A filter can trap emboli, preventing them from reaching the lungs.
Inferior Vena Cava Filters: One Way to Prevent Pulmonary Embolism
Pulmonary embolism treatment begins with treating the symptoms. Oxygen is given if blood oxygen levels are low. Analgesics may be needed to relieve pain. If blood pressure is low, intravenous fluids are given and sometimes drugs that increase blood pressure are given. Mechanical ventilation (a breathing tube) may be needed if respiratory failure develops.
Anticoagulant drugs are given to thin the blood, helping blood flow more freely, and thus prevent existing blood clots from enlarging and additional clots from forming. Drug options include heparin, fondaparinux, newer oral anticoagulants, such as apixaban, rivaroxaban, edoxaban, and dabigatran, or occasionally warfarin.
Heparin is given intravenously and therefore works quickly and can be quickly reversed. However, heparin requires frequent blood tests to monitor the effect and continued hospitalization. Low molecular weight heparin and fondaparinux are given subcutaneously once or twice a day. This advantage also allows these drugs to be used after the person is discharged from the hospital.
When edoxaban or dabigatran is used, doctors must give heparin therapy (by vein or by injection under the skin) for the first 5 to 10 days of therapy before they can give the edoxaban or dabigatran, which sometimes means the person must remain in the hospital. In contrast, when rivaroxaban or apixaban is used, heparin therapy is sometimes unnecessary if pulmonary emboli are small. When warfarin therapy is selected, both heparin and warfarin are given for the first 5 to 10 days of therapy, and then warfarin alone is used thereafter.
Warfarin therapy requires periodic blood testing to ensure that the blood is thin enough to prevent clots from forming but not so thin as to cause a bleeding tendency (called excessive anticoagulation). The warfarin dose is frequently adjusted based on the results of the blood tests. Also, warfarin interacts with many different types of food and with other drugs, which can result in blood that is too thin or too thick. If excessive anticoagulation occurs, severe bleeding in a number of body organs can develop.
Because many drugs can interact with warfarin, people who take anticoagulants should be sure to check with their doctor before taking any other drugs, including drugs that can be obtained without a prescription (over-the-counter drugs) such as acetaminophen or aspirin, herbal preparations, and dietary supplements. Foods that are high in vitamin K (which affects blood clotting), such as broccoli, spinach, kale, and other leafy green vegetables, liver, grapefruit and grapefruit juice, and green tea, may need to be either eaten in very consistent amounts or avoided.
The newer anticoagulants, such as apixaban, rivaroxaban, edoxaban, and dabigatran, have several advantages over heparin or warfarin. Like warfarin, these drugs can be taken by mouth, but dose adjustments and tests to monitor the level of anticoagulation are not needed. Furthermore, these drugs do not often interact with food or other drugs and are less likely to cause severe types of bleeding when compared with warfarin. Rivaroxaban should always be taken with food. It is not clear whether these drugs should be taken by people who are larger than about 120 kg (approx 260 lbs).
How long anticoagulants are given depends on the person’s situation. If pulmonary embolism is caused by a temporary risk factor, such as surgery, treatment is given for 3 months. If the cause is some longer-term problem, such as prolonged bed rest, treatment usually is given for 6 to 12 months, but sometimes it must continue indefinitely. For example, people who have recurrent pulmonary embolism, often because of a hereditary clotting disorder or cancer, usually take anticoagulants indefinitely. Newer research studies have shown that in many people in whom rivaroxaban or apixaban are continued after 6 months, reducing the dose decreases risk of bleeding risk and still prevents most recurrent clots.
Thrombolytic drugs ("clot busting drugs") such as alteplase (tPA) break up and dissolve blood clots. Because these drugs can cause dangerous or fatal bleeding, they are usually only used in people who appear to be in danger of dying due to the pulmonary embolism. Except in the most dire situations, these drugs are usually not be given to people who have had surgery in the preceding 2 weeks, are pregnant, have had a recent stroke, or tend to bleed excessively.
In some centers, if a person appears to be in danger of dying from a massive pulmonary embolism, doctors may try to break up the embolus using a catheter inserted into the pulmonary artery.
Surgery may be needed in some cases of severe embolism. Removal of the embolus from the pulmonary artery may be lifesaving. Surgery is also used to remove long-standing pulmonary artery clots that cause persistent shortness of breath and high pressures in the pulmonary artery (pulmonary hypertension).
A filter can be surgically placed in the main vein in the abdomen that drains blood from the legs and pelvis to the right side of the heart. Such a filter can be used if emboli recur despite anticoagulant treatment or if anticoagulants cannot be used or cause significant bleeding. Because clots generally originate in the legs or pelvis, this filter usually prevents them from being carried into the pulmonary artery. Newer filters are removable. Removal helps prevent some complications that can occur when filters are left in place permanently.