Next Lesson - Asthma
Core
An embolus is material carried in the bloodstream from its site of origin to another site, where it may obstruct a vessel. A thrombus is a clot formed at its original site; a detached fragment travelling through the circulation is a thromboembolus.
A pulmonary embolism (PE) is therefore material that has moved from one part of the vasculature, through the right side of the heart, and lodges in the pulmonary arteries.
An embolus is usually made from a blood clot (thromboembolism), but can also be formed from tumour, air, fat, or amniotic fluid - note that the rest of this article will be focussing on thromboemboli. Pulmonary emboli are the third most common cause of cardiovascular death, after myocardial infarction and stroke, and are one of the most common causes of potentially preventable death in hospital patients. Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is also the third most common cardiovascular disease.
Most pulmonary thromboemboli arise from a deep vein thrombosis (DVT) in the legs or pelvis. A detached clot travels through the right heart before lodging in the pulmonary arteries. The main factors that contribute to thrombus formation are stasis of blood flow (slow or still blood), hypercoagulability of blood (blood that clots too easily), and endothelial injury (damage to the lining of the blood vessel). Together these are known as Virchow’s Triad. The risk factors for a DVT (and therefore PE) are factors that contribute to one or more parts of this triad:
- Pregnancy
- Prolonged immobilisation (e.g. post-operatively or on a long-haul flight)
- Previous venous thromboembolism
- Combined oral contraceptive pill
- Cancer
- Obesity
- Hormone replacement therapy (HRT) taken by mouth. The risk is not increased with transdermal HRT (given through the skin, for example as patches or gel).
Diagram - Virchow's Triad: the relationship between endothelial injury, hypercoagulability, and venous stasis
Creative commons source by Dr.Vijaya chandar, MBBS [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
The above risk factors can be divided into two groups:
- Temporary; for example, pregnancy, the pill, and immobilisation.
- Persistent while present; for example, active cancer. Risk factors can change over time and should be reassessed.
About one-third to one-half of VTE episodes have no identifiable risk factor. The rest are caused by temporary (transient) or persistent risk factors. Prevention of a PE is worthwhile. For example, on a journey of 4 hours or more the NHS advises people to walk around whenever they can, to bend and straighten their legs, feet and toes every 30 minutes while seated, to drink water regularly and to wear flight socks.
Pulmonary emboli cause mechanical obstruction of pulmonary arteries. Obstruction and pulmonary vasoconstriction (narrowing of the lung blood vessels, driven by chemical signals including serotonin and thromboxane) increase pulmonary vascular resistance (the resistance to blood flow through the lungs) and right ventricular afterload (the pressure the right ventricle must pump against). The right ventricle may dilate and fail, reducing blood flow through the lungs and filling of the left ventricle. Cardiac output and systemic blood pressure can then fall. Acute right ventricular failure is the principal lethal mechanism in severe PE.
Ventilated lung supplied by an obstructed artery becomes poorly perfused, increasing alveolar dead space (air in the lung air sacs that reaches no blood flow, so no gas exchange takes place there). Redistribution of blood to other lung regions can produce low ventilation-perfusion ratios (areas where blood flow is high compared with air flow), contributing to hypoxaemia (low blood oxygen). Reduced cardiac output and atelectasis (collapse of part of the lung) can also contribute. Hyperventilation (fast, deep breathing) commonly lowers arterial CO2, so PE may cause type 1 respiratory failure: low arterial O2 with normal or low CO2. Normal oxygen saturation does not exclude PE.
The part of the lung that is poorly perfused may undergo infarction (death of tissue from loss of blood supply). The bronchial arteries, which supply the lung tissue itself, can often provide enough oxygen to prevent this, but infarction is not rare: one review reports an incidence of around 30%. A patient with pulmonary infarction may present with haemoptysis (coughing up blood) and pleuritic chest pain (sharp chest pain that is worse on breathing in).
In a patient with a patent foramen ovale (a small hole between the two atria that stays open), PE-related elevation of right atrial pressure can permit right-to-left shunting (blood passing from the right side of the heart to the left without going through the lungs). A venous embolus may then cross into the arterial circulation, causing a paradoxical embolism (an embolus from a vein that reaches the arteries), including stroke. The risk depends on the presence of a shunt; PE does not make every patent foramen ovale shunt right to left.
Symptoms of a PE include:
- Shortness of breath
- Pleuritic chest pain (sharp chest pain that is worse on breathing in)
- Cough
- Substernal chest pain (behind the breastbone)
- Fever
- Haemoptysis (coughing up blood)
- Syncope (fainting)
- Unilateral leg pain (DVT)
Signs of a PE include:
- Tachypnoea (fast breathing)
- Tachycardia (fast heart rate, over 100 beats per minute)
- Low BP
- Raised jugular venous pressure
- Pleural rub (a scratching sound heard through a stethoscope, from inflamed lung lining) in cases of pulmonary infarction
- Evidence of DVT, e.g. erythema (redness), increased temperature and tenderness on palpation of the leg
The main differential diagnoses for a pulmonary embolism are pneumothorax (air in the space around the lung), pneumonia, musculoskeletal chest pain, and myocardial infarction.
In a patient with a suspected PE, NICE advises that the first step is to estimate the clinical probability with the two-level Wells score (see below). The result decides the next test. The other investigations listed here help to look for other causes and to show the effects of a PE:
- Arterial Blood Gas (ABG) - a blood test, taken from an artery, that measures oxygen, carbon dioxide and acidity. It may show respiratory alkalosis (low carbon dioxide, which makes the blood less acidic) with hyperventilation (fast, deep breathing), but findings are variable and a normal result does not exclude PE.
- Chest X-ray - to exclude differentials such as pneumothorax or pleural effusion (fluid around the lung).
- ECG:
- The most common sign of a PE on an ECG is sinus tachycardia (a fast heart rhythm that starts in the heart's normal pacemaker).
- An ECG could show an S1Q3T3 pattern: a large S wave in lead I, and a Q wave with an inverted T wave in lead III (waves are the parts of the heartbeat trace, and leads are the different views of the heart). These are classic signs of right heart strain. The pattern is a well-known textbook finding but is not common in clinical practice.
- There could also be no signs on ECG - a normal ECG cannot rule out a PE.
- D-dimers:
- D-dimer is measured in a blood test. It is a fragment of fibrin (the protein that holds a clot together) that is released into the blood when the body breaks down a clot (a process called fibrinolysis).
- In a patient in whom PE is unlikely (Wells score of 4 points or less), a d-dimer is the next test. A negative d-dimer rules PE out. A positive d-dimer does not confirm PE, so it is followed by a CTPA (or a ventilation-perfusion scan if CTPA is unsuitable). If the d-dimer result will take more than 4 hours, NICE advises interim therapeutic anticoagulation (a full treatment dose of an anticoagulant) while waiting.
- In a patient in whom PE is likely (Wells score of more than 4 points), the pathway does not use a d-dimer. A CT pulmonary angiogram (CTPA, a CT scan of the lung blood vessels) is offered immediately if possible. If a scan cannot be done immediately, NICE advises interim therapeutic anticoagulation until it can.
- A Wells score (a points score that estimates how likely a PE is) should be calculated for any patient in whom a PE is suspected. In pregnancy, the Royal College of Obstetricians and Gynaecologists (RCOG) advises that d-dimer testing should not be performed and that there is no evidence to support estimating the probability of PE before testing, so the pregnancy pathway in the Management section is used instead. The components of the two-level Wells score are:
- Clinical signs and symptoms of a DVT (at least leg swelling and pain on palpation of the deep veins) - 3 points
- PE is the most likely clinical diagnosis - 3 points
- Heart rate >100 beats per minute - 1.5 points
- The patient has been immobilised for more than 3 days or has had surgery in the past 4 weeks - 1.5 points
- Previous PE or DVT - 1.5 points
- Haemoptysis - 1 point
- Malignancy (on treatment, treated in the last 6 months, or palliative) - 1 point
- A score of >4 indicates a PE is likely
- A score of <= 4 indicates a PE is unlikely
- Imaging:
- CT Pulmonary Angiogram (CTPA): a CT scan of the lung blood vessels, using contrast dye injected into a vein
- Ventilation Perfusion Lung Scintigraphy (VQ scan): a scan that compares air flow (ventilation, V) with blood flow (perfusion, Q) in the lungs, using a small amount of radioactive tracer
Pulmonary emboli can be imaged with a CT pulmonary angiogram (CTPA), which is offered first. Ventilation-perfusion lung scintigraphy (a V/Q scan) is an alternative for people who cannot have CTPA, for example because of an allergy to contrast dye, severe kidney impairment or a high risk from radiation. In pregnancy, the RCOG advises a chest X-ray first, then either a V/Q scan or CTPA (CTPA is preferred if the chest X-ray is abnormal). Scan results should be interpreted together with the clinical history.
A patient with a suspected PE should be given O2 if they are hypoxic (have low blood oxygen), and anticoagulation (a medicine that stops clots growing, for example a direct oral anticoagulant (DOAC) or heparin, an injected anticoagulant) where clinically appropriate. Anticoagulation reduces mortality by preventing the thrombus from propagating (growing) in the pulmonary artery and allowing the body’s fibrinolytic system (its own clot-dissolving system) to break the thrombus down. It reduces the frequency of further embolism but doesn’t dissolve the clot already present.
For a confirmed PE, NICE advises apixaban or rivaroxaban (both DOACs) as the first choice. If neither is suitable, the options are low molecular weight heparin (LMWH) for at least 5 days followed by dabigatran or edoxaban (other DOACs), or LMWH together with a vitamin K antagonist (an anticoagulant tablet such as warfarin). Other choices apply in some groups, for example people with active cancer or kidney impairment, and for a PE with haemodynamic instability NICE advises a continuous infusion of unfractionated heparin (see below). In pregnancy, LMWH is used (RCOG).
Patients with a confirmed PE and haemodynamic instability (a dangerously low blood pressure or poor circulation caused by the PE) may also require haemodynamic support (treatment to support the circulation), respiratory support, and thrombolytic therapy (a drug that dissolves the clot). NICE advises a continuous infusion of unfractionated heparin (UFH, a form of heparin given into a vein) for these patients and that thrombolysis is considered. It advises against systemic thrombolysis in patients with a PE who are haemodynamically stable. Catheter-directed techniques are reserved for selected cases in specialist settings. Procedures used to remove the embolus include percutaneous catheter directed thrombectomy (removal of the clot through a thin tube passed into a blood vessel through the skin), or surgical pulmonary embolectomy (removal of the clot by open surgery).
After 3 months of anticoagulation for PE (3 to 6 months in people with active cancer), reassess the benefits and risks of continuing, stopping or changing treatment with the patient.
- For a provoked PE (one with a clear temporary trigger, such as surgery), consider stopping after the recommended initial course if the provoking factor has resolved and the clinical course has been uncomplicated.
- For an unprovoked PE (one with no identifiable trigger) or an ongoing risk factor, consider longer-term treatment according to the balance between recurrent VTE and bleeding risk, taking the patient's preferences into account. Continuing indefinitely is not automatic.
Edited by: Dr. Marcus Judge
Reviewed by: Dr. Maddie Swannack
- 6475
