An embolus is a “travelling clot” and pulmonary embolism (PE) is a complication of deep venous thrombosis (DVT) clot formation in a vein elsewhere in the body. The clot or clots break off (now called an embolus) and travel through the veins and the right side of the heart, and blocks one or several lung arteries, preventing blood flow to parts of the lung. This results in less oxygen reaching the rest of the body. There are many known risk factors for this condition. Diagnosis may be missed or delayed due to non-specific symptoms, but special tests can be done and specific treatment started. With correct diagnosis and early treatment, the outcome is favourable, and recurrences can be prevented.
Pulmonary thromboembolism is the sudden occlusion of a lung artery due to a blood clot that was dislodged from somewhere else in the body, usually the legs. This leads to obstruction of the blood supply to the lung tissue, Clots can be of different sizes and more than one clot can break off over time. The larger the clot, the greater the risk of sudden death. If not treated aggressively, it can lead to respiratory and/or circulatory collapse and death.
The results and clinical picture of the PE will depend on how large the embolus is: a large embolus will block a major (large) lung artery, whilst a small embolus will reach a smaller, peripheral lung artery before becoming stuck and blocking it off. Blocking a small artery affects only a small part of the lung and may either be asymptomatic or cause any of the symptoms listed below. Blocking a large central artery affects more – sometimes the whole of – one or even both lungs, and will thus produce the sudden, dramatic symptoms described below. Obstructing lung arteries raises the pressure against which the right ventricle of the heart has to pump; in severe cases, this can cause sudden heart failure.
What causes PE?
The causes of pulmonary embolism are basically the same as the causes of venous thrombosis. The causes can be divided into three categories:
- damage to the venous endothelium (lining of the vein) due to indwelling catheters, injection of irritating substances into the vein, sepsis, etc.
- increased coagulability (e.g. blood disorders, cancers, oral contraceptives, etc.)
- venous stasis (postoperative, after child birth, varicose veins, etc.)
More than 90% of pulmonary emboli primarily originate from a deep vein thrombosis (DVT) of the leg, but they can also arise from the abdomen and rarely the arms. The higher up the leg the clot forms, the more likely it is to break off and embolise to the lungs. Less than 20% of lower leg (calf) DVTs will extend upwards into the iliofemoral (thigh) veins, where about 50% break off and travel to the lungs.
The risk factors for developing thrombosis and thus PE can be divided into major (where the risk is greater than 5-20 times normal) and minor (where the risk is 2-4 times normal).
Major risk factors include the following:
- trauma (including fractures, especially of the femur, hip and pelvis)
- surgery within the last 3 months (especially of the hip, knee and abdomen or pelvis)
- malignancy/cancer (especially of lung, pancreas or colon)
- prolonged immobilisation/inactivity (in bedridden patients, e.g. strokes, spinal cord injury, severe burns, etc.)
- pregnancy & Caesarean section (especially post-delivery)
- varicose veins
- previous DVT or PE-existing respiratory disease.
Minor risk factors include:
- oestrogen-containing contraceptive pills and hormone replacement therapy (HRT)
- general medical illness (e.g. heart disease, lung disease, hypertension, TB, kidney disease causing nephrotic syndrome)
- obesity (BMI > 29kg/m²)
- travel (long distance sedentary, especially by air: “Tourist Class Syndrome”)
- advanced age
- heavy cigarette smoking (>25/day)
- indwelling venous lines.
Some patients develop PE without obvious risk factors and these may have unsuspected abnormalities which favour the development of DVT and PE, e.g. increased levels of clotting factors in their blood.
Symptoms and signs of PE
The symptoms associated with pulmonary embolism can vary from no symptoms at all to sudden death. There is no single symptom or sign that will indicate pulmonary thromboembolism with 100% accuracy. The symptoms and signs also vary according to the presence of underlying heart and lung pathology, the size of the embolus and the area of the embolism. The symptoms and signs can start abruptly (within 5 minutes) and may be intense. The intensity will decrease over days as the clot starts dissolving and the lung starts repairing itself. Symptoms may also recur if more of the clot breaks off and travels to the lungs.
The symptoms (i.e. what the patient reports) of pulmonary embolism include:
- chest pain - mainly pleuritic (usually sharp, stabbing , on one side of the chest or both and aggravated by deep breathing or coughing) – 66%
- shortness of breath – 73%
- cough – 37%
- coughing up blood – 13%.
If there is a very large central embolus (8%), the symptoms are not unlike a heart attack:
- central pressing chest pain
- severe shortness of breath
- dizziness and loss of consciousness
- anxiety & restlessness.
The signs (i.e. what the doctor finds) of pulmonary embolism include:
- increased breath rate – 70%
- obvious DVT - 47%
- increased or irregular pulse– 30%
- low grade fever – 14%
- abnormal breathing sounds – 51%
- signs of right heart strain – 24%
- circulatory collapse (very low blood pressure) – 8%
- cyanosis – blueish tinge to the skin due to decreased oxygen in the blood.
How is PE diagnosed?
The diagnosis of pulmonary thromboembolism is usually suspected clinically on the history and the symptoms and signs. Because the symptoms and signs are so variable and non-specific, accurate diagnosis may be difficult, and important clues to the diagnosis are:
- presence of a known risk factor (see above)
- sudden onset and/or spontaneous improvement and then recurrence of symptoms
- absence of another cause for the symptoms and signs.
Special tests are then used to confirm the diagnosis.
- Routine laboratory blood tests are seldom helpful in confirming the diagnosis of pulmonary thromboembolism. Arterial blood gas measurements may show a decrease in oxygen levels, but this is not specific for PT. Blood levels of D-dimers (a breakdown product of clots) is a useful screening test, as it is very sensitive (95%). Unfortunately it is not specific to DVT and PE, as it is also raised in several other conditions, many of which are risk factors for DVT & PE (e.g. trauma, surgery, infection, cancer, pregnancy and liver disease).
- Chest X-rays are normal in 10-15% of patients and in the remainder show several abnormalities, none of which are specific to and diagnostic of PE: small areas of lung collapse, raised diaphragms, collections of fluid (pleural effusions), opacities in the lung fields and swollen central pulmonary arteries. They are useful to exclude other causes of similar symptoms (e.g. pneumonia, pneumothorax).
- ECGs may show an increased heart rate or signs of right-heart strain, but none of these changes are specific enough to confirm the diagnosis. Again, they are helpful in excluding other disorders that may mimic the symptoms and signs of pulmonary embolism (e.g. myocardial infarction, pericarditis).
- Perfusion Scan (Q scan) or Ventilation/Perfusion Scan (VQ scan) is thetraditional investigation when pulmonary embolism is suspected. A radioactive isotope is injected into a peripheral vein and then gamma cameras take pictures of the lungs from multiple angles This will show if there is a disturbance in blood flow to the areas of the lung which are ventilated (i.e. a mismatched defect, an area which is ventilated but not perfused). A normal scan excludes a PE. Other lung conditions (such as scars, infections, emphysema or asthma) can cause disturbance of ventilation perfusion/relationships and thus this test is not useful in patients with these conditions. The scan is only diagnostic (high probability scan with multiple large mismatched defects) in less than half (40%) of patients with proven PE.
- Computed Tomographic pulmonary angiography (CTPA) (also called Spiral CT with Contrast) has now become the investigation of choice in most hospitals because of the difficulties interpreting Q and VQ scans.
Contrast (a radiopaque dye) is injected into a peripheral vein which highlights the vessels in the lung and then the patient lies inside a tube-like structure where computerised x-rays are taken to demonstrate the clot or clots in the pulmonary artery. It has the advantage of showing the lung fields very clearly and demonstrating other lung pathology. It is also is not affected by abnormalities of the lungs like scars, infections, emphysema or asthma. Modern CT machines with multiple detectors have a sensitivity of over 90% and a specificity of 95%. With this technique, pulmonary angiography is rarely needed. It can also detect if the right side of the heart is enlarged, which is a poor prognostic sign.
Top: central pulmonary "saddle embolus" (arrows) extending into both main pulmonary arteries
Bottom: pulmonary emboli (arrows) in smaller arteries in both lung lower zones
- Pulmonary angiography is the “gold standard” of investigations as it is a very sensitive (95%) and specific test (95%) for pulmonary embolism. It shows the lung arteries just like an angiography of the coronary arteries does in the case of a myocardial infarction, but requires a catheter to be inserted into a central vein (e.g. groin or neck), which is then passed through the right side of the heart and into the central pulmonary arteries. It is an expensive and sometimes dangerous test and requires a specialist cardiologist or interventional radiologist and is thus seldom performed nowadays. Clot in right lower pulmonary artery
- Echocardiograms can show large central PE but are not useful for the commoner peripheral ones.
- Magnetic Resonance Imaging (MRI) is not yet validated and recommended for diagnosing PE, but may be used in difficult cases, or those where use of contrast material is contraindicated (allergy or renal failure).
- Compression Ultrasound (CUS) can be used to demonstrate the associated DVT in the upper legs, but while very specific (95%) it is only 25-50% sensitive in PE patients.
How is PE treated?
All patients should have supportive treatment with bed rest (usually only for a day or two), pain relief and oxygen..
In severe cases with large central or extensive clot, the patient will need to be resuscitated with oxygen (sometimes by positive pressure ventilation), cautious intravenous fluids and possibly drugs to improve the circulation (vasopressors).
Anticoagulants are medications that thin the blood and make it less likely to form clots. Anticoagulation is begun as soon as the diagnosis is suspected in clinically probable cases, even before the diagnosis is confirmed, unless there are absolute contra-indications (e.g. active bleeding or possible major bleeding site). This is because the risk of recurrent embolism and death is highest early on in the course, and early anticoagulation has been proven to have better results. If the tests show that a PE has not occurred, the anticoagulation can be stopped and short-term anticoagulation is relatively safe in good hands Heparin is used initially, as this works quickly to stop more clot forming, the existing clot enlarging or further pieces breaking off. Unfractionated (UF) Heparin is given as an intravenous infusion, but this has problems as its efficacy needs to be monitored by frequent blood tests (the Partial Thromboplastin Time or PTT) and the dose requires varies enormously between patients and even in the same patient over time. Nowadays most patients are given Low Molecular Weight (LMW) Heparin by subcutaneous injection. This is more effective and also safer in most patients. It is also cost-effective as there is a standard dose (PTT monitoring not required) and an intravenous infusion is not needed (patients can be discharged from hospital early or occasionally even managed on an out-patient basis). Heparin by either route is usually given for about 5 days. Because an oral treatment is preferred for the more long-term therapy required for DVT and PE, the patient is also started on Warfarin on the first or second day (once the diagnosis has been confirmed). Warfarin takes several days to become effective, so it is overlapped with the Heparin for 2-4 days and then continued alone. The dose of Warfarin must be carefully monitored by regular INR blood tests, aiming at a value of 2 – 3. If a dose is forgotten, the patient should call their doctor or clinic for advice and the dose should not be changed to make up for missed doses. While taking anticoagulants, patients may bleed easily many areas, such as the skin, nose and gums, as well as have excessive menstrual bleeding, bleeding into the urine or bowel actions (which can contain fresh blood or altered black tarry material). In some cases, bleeding can develop inside the body and not be noticed. This may result in feeling faint or experiencing back or abdominal pain. Several commonly used drugs (e.g. aspirin, non-steroidal anti-inflammatories, some antibiotics) interfere with the action of Warfarin and increase the chance of either bleeding or thrombosis, so patients should be aware of this and always discuss any new drug use with their doctor. They should also wear a Medic-Alert bracelet or necklace at all times.
Warfarin is contraindicated in pregnancy and is less effective in cancer. Long-term subcutaneous LMW Heparin is currently recommended in these patients. Newer oral drugs are becoming available (e.g. Dabigatran), which are as effective as Warfarin, but do not require monitoring blood tests and interact less with other drugs, but are more expensive.
The duration of Warfarin treatment varies. For a first episode, with identified and reversible risk factors, the standard duration of Warfarin therapy is 3 months. For patients with a permanent risk factor (e.g. cancer, long-term immobilization, inherited clotting tendency) or recurrent DVT or PE with no identifiable risk factors, therapy is continued indefinitely. However, the bleeding risk of long-term anticoagulation increases over time so that each patient and their doctor should regularly (at least every 6 months) weigh up the risk of bleeding against the benefit of continuing Warfarin (decreased risk of another clot).
Heparin and Warfarin only prevent more clots from forming and neither dissolves existing clots (thrombolysis). In most patients this is not required, as the body slowly dissolves most of the clot in the pulmonary arteries over time. In severe cases, it is necessary to dissolve the clot actively with intravenous thrombolytic or “clot-busting” drugs: Tissue Plasminogen Activator (TPA), Streptokinase or Urokinase. These are not used routinely as they are more dangerous (have a higher risk of bleeding complications), require ICU care and are more expensive. However, they are indicated in patients who remain shocked (low blood pressure) or oxygen-dependant despite standard care. It is controversial whether they are also indicated in patients with normal blood pressure, but who have evidence of right heart strain. Currently this is not recommended, but is being studied and should become clear in a year or so.
What does one do if thrombolytic therapy fails or is contraindicated (e.g. active bleeding, trauma or surgery within the previous 7-10 days, stroke or brain tumour within the last 3 months, severely uncontrolled hypertension)? Then the embolus must be removed either surgically (requiring an experienced heart surgeon) or via a pulmonary artery catheter (requiring an experienced cardiologist). The latter uses a technique similar to that used for angiograms, where the catheter breaks up the clot and occasionally a very small dose of the thrombolytic drug is infused directly into the clot.
Vena Cava Filters
What does one do if anticoagulant therapy fails (more clots embolise despite adequate anticoagulation) or is contraindicated? Under these circumstances a filter to block the clot migration can be inserted via a groin vein into the inferior vena cava, the large vein which carries all the blood from the lower limbs, pelvis and abdomen to the heart and lungs. These are not used routinely as they are expensive, invasive and increase the chance of further clot-forming behind them in the abdomen and legs.
What is the outcome?
Undiagnosed or untreated PE have a 10-33% risk of death (usually early on in their course) and a 25- 50% risk of further PE. If the diagnosis is made early in the disease and the appropriate treatment is given, the mortality rate is decreased to 2-8% and recurrent PE to 5-10%. If a patient survives the acute episode, he should recover completely with no lasting after effects, although the clot in the lung can take several weeks and occasionally months to dissolve. For some reason in a very small minority of patients (less than 5%), permanent and increasing clot collects and forms in the pulmonary arteries, causing severe right heart strain and failure. This can sometimes occur in the absence of a proven PE beforehand. These patients present with severe shortness of breath, dizziness and leg swelling. Some of these patients can be radically improved by surgery to remove this extensive organised clot (pulmonary endarterectomy).
The long-term outcome will also depend on whether recurrences are prevented.
Lifestyle risk factors, such as obesity and smoking, can be changed. Other known factors, such as post-operative immobility, can be managed by the judicious use of prophylactic (preventative) anticoagulants and early mobilisation. Prophylactic anticoagulation is extremely effective (decreases the risk of DVT and PE by more than 60%) and safe. It should be given to everyone admitted to hospital with a medical illness or to undergo surgery, unless there are contraindications. The presence of risk factors for thrombosis makes this even more necessary. The usual method is a once daily low dose subcutaneous LMW Heparin or 2-3 times daily UF Heparin. A less effective method is the use of inflatable compression devices that are worn around the legs during and immediately after surgery. The devices periodically fill with air and apply gentle pressure to improve circulation and help prevent clots. These can be used together with anticoagulants, or even instead thereof if they are thought to be too risky. Graduated compression stockings may also be recommended; these stockings should be custom fitted to apply pressure to the lower legs, with the greatest pressure at the ankle. The pressure should gradually decrease up to the knee. For all patients, walking as soon as possible after surgery can decrease the risk of a blood clot.
Persons undertaking long flights are encouraged to move regularly (both walking around plus leg exercises while seated) and take adequate fluids. Those with known risk factors or previous DVT or PE should discuss short-term oral or subcutaneous prophylactic anticoagulation with their doctor.
When to see your doctor
If you develop any of the symptoms described - especially if any of the known risk factors apply to you - please go to your nearest doctor or Emergency Unit urgently.
Reviewed by Dr A G Hall, 2007/05/07.
Reviewed by Prof Gillian Ainslie, UCT Lung Institute, September 2010