A pulmonary embolism occurs when a blood clot, generally a venous thrombus, becomes dislodged from its site of formation and embolizes 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, 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.

Electrocardiography (ECG) may occasionally (up to 20%) show right heart strain (the "S1Q3T3 pattern", the McGinn-White pattern).

Risk factors

The most common sources of embolism are pelvic vein thromboses or proximal leg deep venous thrombosis (DVTs). 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"/VTE) can be divided into genetic, acquired and circumstantial causes. In many occasions, more than one risk factor is present:

• Genetic ("thrombophilia")
  • Factor V, Leiden type (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
  • Use of the oral contraceptive pill
• Circumstantial
  • Immobilisation, e.g. after-
    • Surgery
    • Trauma
  • Use of oral contraceptives
  • Obesity
  • Pregnancy
  • Cancer (Trousseau's syndrome)

Diagnosis

Confirming PE

The gold standard for diagnosing pulmonary embolism (PE) is still pulmonary angiography. In most of the cases, however, when PE is suspected on the basis of shortness of breath and chest pain, the following scans may confirm the presence of an embolus:

• "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.
• Increasingly, the V/Q scan is being replaced with computed tomography (spiral CT) with radiocontrast. 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.

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).

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.

Treatment

Acutely, supportive treatments, such as oxygen or analgesia, are often required. Massive PE, as confirmed by imaging or echocardiography, is treated with thrombolysis.

In most cases, anticoagulant therapy is the mainstay of treatment. Heparin or low molecular weight heparins are 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. 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 is often increased to 3.0-4.0 (unless there are contraindications).

Prognosis

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.

History

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.

References

• 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.