BMJ Learning

Pulmonary embolism

د. حسين محمد جمعة
اختصاصي الامراض الباطنة
البورد العربي
كلية طب الموصل
2010

Clinical tip

Around 73% of patients will present with dyspnoea and about 30% with tachycardia. Consider pulmonary embolism in patients with:
Underlying malignancy
New onset atrial fibrillation
Chest wall pain (a rare, but recognised, cause of pulmonary embolism).

It has an untreated mortality of about 30%, and is the commonest cause of death following elective surgery (accounting for up to 15% of all postoperative deaths). It is also the most common cause of maternal death in the UK.
Postmortem studies show it accounts for around 10% of all hospital deaths, emphasising the importance of thromboembolism prophylaxis in patients who are immobile.


Up to 50% of leg thrombi embolise, with a higher incidence in clots above the knee than below the knee.
Large clots may lodge at the bifurcation of the main pulmonary arteries causing haemodynamic compromise. Smaller clots will travel more distally, infarcting the lung and causing pleuritic pain. Thrombi can also propagate from the right heart (in right ventricular failure) or post-myocardial infarction.

Major risk factors (relative risk increased 5-20-fold) include:

Surgery - major and/or abdominal surgery
Lower limb orthopaedic surgery
Obstetrics - late pregnancy (higher incidence with multiple births), caesarian section, pre-eclampsia
Malignancy
fracture, varicose veins
Previous proved venous thromboembolism
prolonged bed rest

Minor risk factors (relative risk increased 2-4-fold) include:

Cardiovascular - congenital heart disease, congestive cardiac failure, hypertension, central venous access
Oestrogens - oral contraceptives (especially "third generation" pills), hormone replacement therapy
Miscellaneous - occult malignancy, neurological disability, obesity, thrombotic and myeloproliferative disorders, nephrotic syndrome, inflammatory bowel disease.

Economy class syndrome

This is long distance sedentary travel, with an increasing incidence of venous thromboembolic disease with increasing distance travelled. There is some debate as to the importance of this causal link because most travellers who develop a venous thromboembolism have additional risk factors.
A study in 2001 of more than 135 million passengers showed an incidence of pulmonary embolism of 1.5 cases per million for travel over 5000 km, compared with 0.01 cases per million for travel under 5000 km. The incidence was 4.8 cases per million for travel over 10 000 km.


Some 25% to 50% of patients with venous thromboembolism have an identifiable inherited thrombophilia, for example:

• Factor V Leiden gene mutation

• Deficiency of antithrombin III
• A prothrombin gene defect
• Protein C deficiency
• Protein S deficiency.
These usually need to interact with an additional acquired risk factor to cause venous thromboembolism.

The current British Thoracic Society guidelines do not advocate routine screening for inheritable thrombophilias because the number needed to test to prevent an episode of venous thromboembolism would be very high. However, screening is warranted in some clinical situations , For example, in
a young woman who has had a first unprovoked episode of venous thromboembolism, who wished to take the oral contraceptive, thrombophilia screening might be warranted.

Who to screen for thrombophilia

Patients younger than 50 with recurrent idiopathic pulmonary embolism (ie those with more than one episode of proved venous thromboembolism, in whom no cause can be identified). Some 50% of these patients will have an identifiable thrombophilia.
Those with a strong family history (ie where symptomatic venous thromboembolism has been proved in several family members in more than one generation).

Rare causes of pulmonary embolism include

Air embolism
Following neck vein cannulation, bronchial trauma, and intrauterine manipulation (rare).
Small amounts of air can be tolerated,
but large amounts can lodge in the pulmonary vasculature and cause mechanical obstruction and death.


Arterial air emboli may cause:
Dizziness
Loss of consciousness
Convulsions (due to air in the cerebral circulation).
Air may be seen in the retinal arteries

Venous air emboli may cause:

Raised venous pressure
Cyanosis
Hypotension
Tachycardia
Syncope.
Treatment is by lying the patient on their right side, with head down and feet up, to allow air to collect and stay at the cardiac apex. From here it can be aspirated. This may be done by ultrasound guided needle aspiration

Amniotic fluid embolism

This is usually catastrophic: 80% of women die, 20% to 50% of these in the first hour.
An anaphylactic-type response to amniotic fluid entering the circulation is seen. The fluid enters circulation because of torn fetal membranes, which can occur in caesarean section, uterine or cervical trauma, or uterine rupture. It has a thromboplastic effect, causing disseminated intravascular coagulation and thrombi to form in pulmonary vessels.

It typically presents with:

Sudden onset respiratory distress
Hypoxia
Bronchospasm
Cyanosis
Cardiovascular collapse
Pulmonary oedema
Convulsions
Coma
Cardiac arrest.
Treatment is supportive: oxygen for hypoxia, fluids and inotropes to maintain an adequate circulation, and fresh frozen plasma for coagulopathy.


Fat embolism
This occurs in association with long bone fractures, with bone marrow fat droplets released into the venous circulation at fracture. It is more common in non-immobilised fractures.

It typically presents with:

Hypoxia
Coagulopathy
Transient petechial rash on neck, axillae, and skin folds
Neurological disturbance, such as confusion.
Fat globules can be identified in the urine.
Treatment is supportive: oxygen for hypoxia, and fluids and ionotropes to maintain an adequate circulation.

How do I diagnose it?

History and symptoms
Pulmonary embolism can be difficult to diagnose. The prevalence of pulmonary embolism in those suspected of the diagnosis is only about 10%. No symptoms or signs are diagnostic, hence the need for careful assessment and diagnostic tests.
Dyspnoea and tachypnoea (defined as a respiratory rate >20) are the most common presenting features, and are absent in only 10% of patients.

Acute pulmonary emboli typically present in four main ways

1. Circulatory collapse in a previously well patient(5%): hypotension ± loss of consciousness. This is usually due to massive pulmonary embolism causing acute right heart failure.
2. Pulmonary infarction syndrome (60%): typically presents with pleuritic pain, with or without haemoptysis. Localising signs, eg a pleural rub, may also be present.
3. Isolated dyspnoea (25%): acute breathlessness without haemorrhage or circulatory collapse. This typically presents with sudden onset shortness of breath in the presence of risk factors for pulmonary embolism.
4. Collapse, poor reserve (10%): classically in an elderly patient with limited cardiorespiratory reserve; a small pulmonary embolism can be catastrophic.


Pulmonary embolism should be included in the differential diagnosis of patients with:
• Unexplained breathlessness
• Collapse
• New onset atrial fibrillation
• Pleural effusion
• Right heart failure.

Examination

May be completely normal, but tachycardia (classically with a loud P2 and splitting of the second heart sound) with tachypnoea are common
May present with atrial fibrillation, reduced chest movement (due to pain), or a pleural rub
Hypoxia is common but in young, otherwise healthy, individuals, the oxygen saturation may be normal
Signs of a deep vein thrombosis are present in about 25%

Investigations

The pre-test clinical probability score is an assessment of the clinical likelihood of pulmonary embolism, based on clinical assessment and the presence of risk factors.

British Thoracic Society pre-test probability scor

A standard assessment of pre-test clinical probability might include:

A
Patient has clinical features compatible with pulmonary embolism (raised respiratory rate, ± haemoptysis, ± pleuritic chest pain)
Plus two other factors:


1
Absence of another reasonable clinical explanation
2
Presence of a major risk factor
A plus 1 and 2:
High pre-test clinical probability
A plus 1 or 2:
Intermediate pre-test clinical probability
A alone:
Low pre-test clinical probability

The score includes clinical features consistent with pulmonary embolism (including a raised respiratory rate, haemoptysis, and pleuritic chest pain).
Heart rate is not included in most standard scores.

The pre-test clinical probability score should always be used with the D-dimer test .

A low pre-test clinical probability score, combined with a negative D-dimer test has about a 90% sensitivity at excluding pulmonary embolism.

Pregnancy

The diagnosis can be difficult to make in women who are pregnant. The standard pre-test clinical probability score should be used, recognising that pregnancy is a major risk factor for venous thromboembolism. The D-dimer test is of no use in this situation because it is raised (in the absence of pulmonary embolism) from about six weeks' gestation, and remains elevated until about three months post-partum.

If there is a clinical suspicion ,chest x ray is mandatory, and should not be delayed because of concerns about radiation to the fetus.
CTpulmonary angiography and V/Q carry a much greater radiation risk (whole body radiation dose of 2-4 mGy and 1.5-2 mGy respectively, absorbed fetal dose 0.01 mSv and 0.12 mSv respectively); these must be discussed with the pregnant woman.


Some advocate leg ultrasound as a first line investigation. If an asymptomatic DVT is confirmed in the setting of clinical features suggestive of pulmonary embolism, then treatment may be started without the need for radiation exposure from further imaging. The risk of delayed or non-diagnosis may impose a greater threat to the mother and unborn child.

First line investigations

Electrocardiogram
Non-specific changes are frequent, sinus tachycardia is most common. Atrial fibrillation, right bundle branch block, and anterior T wave inversion (indicating right ventricular strain) are common. The S1Q3T3pattern (where the ECG shows an S wave in I, a Q wave in lead III, and T wave inversion in lead III) is uncommon.

Chest x ray

No specific features are characteristics in pulmonary embolism, but it may reveal another pathology. Small effusions are present in 40% of patients.
Arterial blood gas
This may be normal. Hypoxia and hypocapnia, with an increased A-a gradient, is common.

D-dimer test

This is useful only for excluding pulmonary embolism, and should be used only with the pre-test clinical probability assessment. D-dimers are released as a result of fibrinolysis, and indicate the presence of intravascular thrombus.

A negative D-dimer test reliably excludes pulmonary embolism in patients with a low pre-test clinical probability.

A negative test is unhelpful in those with a high clinical probability (and therefore should not be done in this situation).

Computed tomographic pulmonary angiogram (CTPA)

This is now recommended as the initial imaging technique in suspected non-massive pulmonary embolism. It has a sensitivity of greater than 95%, and enables an alternative diagnosis to be made if pulmonary embolism is excluded.


Troponin
Troponin and natriuretic peptides are sensitive markers of right ventricular dysfunction, and early data suggest a raised troponin predicts poorer prognosis.
Echocardiogram
This can detect right heart strain and a high pulmonary artery pressure (PAP) which may be caused by acute thromboembolism or chronic pulmonary arterial hypertension.

Isotope lung scan (ventilation/perfusion scan)

This is mostly now superseded by CTPA.
It may be useful as a first line imaging investigation only in patients with a normal chest x ray and with no concurrent cardiopulmonary disease.
In these patients a negative scan reliably excludes pulmonary embolism.

The clinical significance of the lung scan report is:

Normal = no pulmonary embolism
Low or intermediate pre-test clinical probability plus low probability scan = pulmonary embolism excluded
High pre-test clinical probability plus high probability scan = pulmonary embolism diagnosed.

Second line investigations

Leg ultrasound
Up to 50% of patients with a clinically obvious deep vein thrombosis will have a high probability V/Q scan,


and conversely around 70% of patients with proved pulmonary embolism will have a proximal deep vein thrombosis.

Conventional pulmonary angiogram

This is rarely needed, and would be performed only in a specialist centre.
CT venography
This can be combined with CTPA to image the leg veins simultaneously.

How should I treat it?

Supportive treatment
Is vital for all patients with suspected pulmonary embolism. It involves maintaining oxygenation, usually with high flow oxygen with a non-rebreather bag.
It is also vital to ensure that an adequate circulation is maintained. This may involve using fluids and ionotropes in massive pulmonary embolism.

Anticoagulation

Low molecular weight heparin should be started in those with a high or intermediate pre-test clinical probability before imaging.
One randomised controlled trial showed no difference between LMWH (tinzaparin) and unfractionated heparin (ie intravenous heparin) in mortality or further episodes of VTE in a group of 612 patients with symptomatic pulmonary embolism.
There was no difference in bleeding complications between the two treatment groups.

Usual length of treatment is three or six months for a first idiopathic pulmonary embolism. A British Thoracic Society trial comparing three and six months' treatment is ongoing.
This is an area of some debate. No guidelines exist for length of treatment for recurrent idiopathic pulmonary embolism. This depends on the individual, the risk of recurrence, and risk of bleeding on warfarin. Lifelong anticoagulation may be recommended for patients with persisting risk factors

Patients with malignancies. The CLOT study assessed anticoagulation with warfarin or LMWH (dalteparin) in patients with cancer and acute venous thromboembolism. It showed that six months' dalteparin treatment was more effective than six months' oral anticoagulation in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.


Caval Filter. Consider when a patient has recurrent thromboembolism despite adequate anticoagulation or when anticoagulation is contraindicated. They are usually for short term use only. They do prevent emboli though there are no data to show they affect mortality. May also be indicated in patients who survive acute massive pulmonary embolism (in whom a second pulmonary embolism may be fatal)

• A very small minority with recurrent venous thromboembolism (despite adequate anticoagulation) may benefit from filter placement.
• May also be indicated in patients who survive acute massive pulmonary embolism (in whom a second pulmonary embolism may be fatal)
• Those with acute VTE in whom there are absolute contraindications to anticoagulation.
Inferior vena caval filter

Flight prophylaxis. Current British guidelines suggest considering aspirin or LMWH, or formal anticoagulation for those at high risk of pulmonary embolism (that is patients with previous venous thromboembolism or malignancy). There is, however, limited evidence to support this. Compression stockings may be beneficial.

Thrombolysis is an area of some debate. The current British Thoracic Society guidelines recommend thrombolysis for acute massive pulmonary embolism, ie pulmonary embolism causing cardiovascular collapse. In practice this is usually given in the peri-arrest situation, where there is no time for investigations.
A bolus of alteplase 50 mg iv is suggested.

For submassive pulmonary embolism, the treatment is more controversial. Some evidence now supports the use of thrombolysis for haemodynamically stable submassive pulmonary embolism, in association with pulmonary hypertension or right ventricular dysfunction.
The dose of alteplase recommended is 100 mg iv over 90 minutes.

Clot fragmentation using mechanical techniques via a right heart catheter and embolectomy may be life saving if there are absolute contraindications to thrombolysis. But these are rarely done, and available in few centres.

Between 25% and 50% of patients with venous thromboembolism have an identifiable thrombophilia. These include:
• Antiphospholipid syndrome
• Antithrombin III deficiency
• Protein C deficiency
• Protein S deficiency
• Prothrombin gene defects.
• Factor V Leiden gene mutation


Heterogenous factor V Leiden deficiency is found in 5% of the population, but in around 20% of those with venous thromboembolism.
Only factor V Leiden (a genetic test) can be tested for while the patient is on anticoagulants. All other risk factors must be tested for off anticoagulation.

Unfractionated heparin has a quicker onset of action than low molecular weight heparin, and it is recommended in massive and submassive pulmonary embolism,
or where rapid reversal of anticoagulation may be needed.

Anticoagulation should be given for six weeks after delivery, or for three months following the initial episode, whichever is longer.
Warfarin is safe during breast feeding.

Warfarin is teratogenic and is contraindicated in the first trimester. Low molecular weight heparin may be recommended nearer time of delivery, though some centres advocate the use of warfarin in the second and third trimesters. Close liaison between the obstetric team, haematology, and respiratory specialists is needed.

Leg ultrasound is only up to about 50% sensitive for detecting deep vein thrombosis. Venography is about 60% sensitive

The S1Q3T3 ECG pattern is uncommon and is not diagnostic, but it may raise suspicion. Sinus tachycardia is the most common ECG finding.

Any patient who has had a previous deep vein thrombosis or pulmonary embolism should be advised against the oral contraceptive.
The risk of pulmonary embolism increases throughout pregnancy, with more pulmonary emboli occurring after delivery than before.
The risk of pulmonary embolism in pregnancy increases with maternal age and multiple births.

CTPA has a sensitivity of over 95%. V/Q scanning is less sensitive, Subsegmental clot is seen better on conventional pulmonary angiography, but better scanning protocols and thin section scanning mean this is less of a problem. The latest CT technology allows better diagnosis of more peripheral thrombus. CTPA has a sensitivity of over 95%. V/Q scanning is less sensitive, but can be useful if the chest x ray is normal,


What should the next step be in a patient with a high probability V/Q scan, but a low pre-test probability score? When there is discordance between the lung scan and clinical probability score, a computed tomographic pulmonary angiography is the recommended next investigation. The diagnosis must be confirmed, or the pre-test clinical probability must be intermediate or high before anticoagulation is started.

Up to 50% of patients with a clinically obvious deep vein thrombosis will have a high probability V/Q scan and, conversely, around 70% of patients with proved pulmonary embolism will have a proximal deep vein thrombosis. Leg ultrasound can be used as an initial test to exclude the need for lung imaging because the identification of a deep vein thrombosis excludes the need for other tests in the appropriate clinical scenario.

the identification of a deep vein thrombosis excludes the need for other tests in the appropriate clinical scenario.

Follow up

Hospital patients are usually followed up at about six weeks following discharge, and should have regular INR monitoring, usually via the hospital anticoagulation service. Closer outpatient follow up may be recommended if the patient has significant comorbid disease or if anticoagulation was difficult in hospital.

If the patient is otherwise well, they may be seen once more at the end of their warfarin treatment period (three or six months) to ensure they have no ongoing symptoms that might suggest chronic thromboembolic disease (ie significant persistent ongoing breathlessness, for which there is no other explanation). This is rare, occurring in no more than 4% of pulmonary embolic event survivors at two years. It is due to incomplete clot resolution within the lung.

What's the outlook?

For survivors of acute pulmonary embolism, the outlook is very good. Most will have no future problems, and just need careful warfarin monitoring (INR) for three to six months.