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Pulmonary embolism

A pulmonary embolism (thromboembolism) occurs when a blood clot, generally a venous thrombus, becomes dislodged from its site of formation and embolises to the arterial blood supply of one of the lungs. Symptoms may include difficulty breathing, pain during breathing, and more rarely circulatory instability and death. Treatment is with anticoagulant medication, such as warfarin.

Signs, symptoms and risk factors

Clinical presentation

Signs of PE are sudden-onset dyspnea (shortness of breath, 73%), tachypnea (rapid breathing, 70%), chest pain of “pleuritic” nature (worsened by breathing, 66%), cough (37%), hemoptysis (coughing up blood, 13%), and in severe cases, cyanosis, tachycardia (rapid heart rate), hypotension, shock, loss of consciousness, and death. Although most cases have no clinical evidence of deep venous thrombosis in the legs, findings that indicate this may aid in the diagnosis.

Risk factors

The most common sources of embolism are proximal leg deep venous thrombosis (DVTs) or pelvic vein thromboses. Any risk factor for DVT also increases the risk that the venous clot will dislodge and migrate to the lung circulation, which happens in up to 15% of all DVTs.

Risk factors for DVT and PE (together “venous thromboembolism” or VTE) can be divided into genetic, acquired and circumstantial causes. In many occasions, more than one risk factor is present:

  • Genetic
    • Factor V Leiden (3% of the population are heterozygous for FVL).
    • Prothrombin mutation (G20210A).
    • Protein C deficiency.
    • Protein S deficiency.
    • Antithrombin III deficiency.
    • High homocysteine levels due to MTHFR mutation.
    • Plasminogen and fibrinolysis disorders.
  • Acquired
    • Antiphospholipid antibodies
    • Anticardiolipin antibodies and/or lupus anticoagulants
    • Renal disease (renal loss of antithrombin)
    • Paroxysmal nocturnal hemoglobinuria
  • Circumstantial
    • Immobilisation, e.g. after surgery or trauma
    • Use of oral contraceptives
    • Obesity
    • Pregnancy
    • Cancer ( as in Trousseau’s syndrome)


Confirming pulmonary embolism

The gold standard for diagnosing pulmonary embolism (PE) is pulmonary angiography. In most cases, however, when PE is suspected on the basis of shortness of breath and chest pain, the following studies may confirm the presence of an embolus. Pulmonary angiography is used less often because of wider acceptance of CT scans which are non-invasive.

Computed tomography with radiocontrast, effectively a pulmonary angiogram imaged by CT, is increasingly used as the mainstay in diagnosis. Advantages are clinical equivalence, better access for patients and the possibility of picking up other lung disorders from the differential diagnosis in case there is no pulmonary embolism.

“Ventilation-perfusion scan” (or V/Q scan), which shows that some areas of the lung are being ventilated but not perfused with blood (due to obstruction by a clot). It is a type of scintigraphy. This study is used less often because of CT technology, however, it may be useful in patients who have an allergy to iodinated contrast

In low/moderate suspicion of PE, a normal D-dimer level (shown in a blood test) is enough to exclude the possibility of PE (Bounameaux et al 1994).

An electrocardiogram may show signs of right heart strain or acute cor pulmonale in cases of large PEs – the classic signs are a large S wave in lead I, a large Q wave in lead III and an inverted T wave in lead III (“S1Q3T3”, as described by McGinn & White 1935). This is occasionally (up to 20%) present, but may also occur in other acute lung conditions and has therefore limited diagnostic value; The most commonly seen sign in the ECG is sinus tachycardia.

In massive PE, dysfunction of the right side of the heart can be seen on echocardiography, an indication that the pulmonary artery is severely obstructed and the heart is unable to match the pressure. In the United States, many physicians see this as an adequate indication for thrombolysis (see below).

The presence of deep venous thrombosis is in itself enough to warrant anticoagulation, without requiring the V/Q or spiral CT scans, and leg ultrasound can be used as a surrogate. This may be valid approach in pregnancy, in which the other modalities would increase the risk of birth defects in the unborn child. However, a negative scan does not rule out PE, and low-radiation dose scanning may be required if the mother is deemed at high risk of having pulmonary embolism.

Further analysis

When a PE is being suspected, a number of blood tests are also done, in order to exclude important secondary causes of PE. This includes a full blood count, clotting status (PT, APTT, TT), and some screening tests (erythrocyte sedimentation rate, renal function, liver enzymes, electrolytes). If one of these is abnormal, further investigations might be warranted.


Acutely, supportive treatments, such as oxygen or analgesia, are often required.

Massive PE causing hemodynamic instability (marked decreased oxygen saturation, tachycardia and/or hypotension) is an indication for thrombolysis, the enzymatic destruction of the clot with medication. Some advocate its use also if right ventricular dysfunction can be demonstrated on echocardiography (see e.g. Goldhaber 2004).

In most cases, anticoagulant therapy is the mainstay of treatment. Heparin, low molecular weight heparins, or fondaparinux is administered initially, while warfarin therapy is commenced (this may take several days, usually while the patient is in hospital). Warfarin therapy is usually continued for 3-6 months, or “lifelong” if there have been previous DVTs or PEs, or none of the usual risk factors is present.

Warfarin therapy often requires frequent dose adjustment and monitoring of the INR. In PE, INRs between 2.0 and 3.0 are generally considered ideal. If another episode of PE occurs under warfarin treatment, the INR window may be increased to e.g. 2.5-3.5 (unless there are contraindications) or anticoagulation may be changed to a different anticoagulant e.g. low molecular weight heparin.

In patients with an underlying malignancy, therapy with a course of low molecular weight heparin may be favored over warfarin based on the results of the CLOT trial (Lee et al, 2003). If anticoagulant therapy is contraindicated and/or ineffective an inferior vena cava filter may be implanted.


Before anticoagulation became the accepted treatment, mortality from PE was about 26% (Baritt & Jordan 1960).

Prognosis depends on the amount of lung that is affected and on the co-existence of other debilitating conditions. Chronic embolisation to the lung can lead to pulmonary hypertension.

After a first PE, the search for secondary causes is usually brief. Only when a second PE occurs, and especially when this happens while still under anticoagulant therapy, a further search for underlying conditions is undertaken. This will include testing (see above for full list) for Factor V Leiden mutation, antiphospholipid antibodies, protein C and S and antithrombin levels, and later prothrombin mutation, MTHFR mutation, Factor VIII concentration and rarer inherited coagulation abnormalities.


After a trial published in 1960 (Baritt & Jordan), anticoagulation became the most important therapeutic intervention in pulmonary embolism. Barritt and Jordan performed their study in the Bristol Royal Infirmary in 1957. This study rapidly set the pace, considering that no other study of anticoagulation in PE ever had a placebo group (as this would have been unethical). Looking back, the reported mortality rate of 26% may have been an overstatement, given the fact that with the technology of the day, only severe PEs were detected.

One notable victim of pulmonary embolism was William II, the last Kaiser of Germany.


  • Barritt DW, Jorden SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet 1960;1:1309-1312. PMID 13797091.
  • Bounameaux H, de Moerloose P, Perrier A, Reber G. Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost 1994;71:1-6. PMID 8165626.
  • Goldhaber SZ. Pulmonary embolism. Lancet 2004;363:1295-305. PMID 15094276.
  • PMID 12853587
  • McGinn S, White PD. Acute cor pulmonale resulting from pulmonary embolism. J Am Med Assoc 1935;104:1473–1480.