Article: Pulmonary embolism

Pulmonary embolism is a blockage of an artery in the lungs by a blood clot, fat, air or clumped tumor cells. By far the most common form of pulmonary embolism is a thromboembolism, which 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. Other rarer forms of pulmonary embolism occur when material other than a blood clot is responsible. Such materials can include fat or bone (usually in association with significant trauma), air (often when diving), and amniotic fluid (affecting mothers during child-birth).

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 (DVT) in the legs, findings that indicate DVT 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)

Diagnosis

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.^[1]

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").^[2] 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 (EKG), 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 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.^[3]

Medical management

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.^[4] If anticoagulant therapy is contraindicated and/or ineffective an inferior vena cava filter may be implanted.

Thrombolysis

Thrombolysis can be given for severe PEs when surgery is not immediately available or possible (e.g. periarrest or during cardiac arrest). The use of thrombolysis in moderate PEs is still debatable. The aim of the therapy is to dissolve the clot, but there is an attendant risk of bleeding or stroke.

Tissue plasminogen activator (tPA): 100mg IV over 2 hours then IV heparin for 48 hours aiming to keep the APTT ratio between .

Streptokinase 250 000 units IV over an hour, followed by 100 000 units IV per hour for 24 hours. The infusion can be continued to 72 hours if there is a concurrent DVT.

Surgical management of PE

Acute

Surgical management of acute pulmonary embolism (pulmonary thrombectomy) is uncommon and has largely been abandoned because of poor long-term outcomes. However, recently, it has gone through a resurgence with the revision of the surgical technique and is thought to benefit selected patients.^[5]

Chronic

Chronic pulmonary embolism leading to pulmonary hypertension (known as chronic thromboembolic hypertension) is treated with a surgical procedure known as a pulmonary thromboendarterectomy.

Prognosis

Mortality from untreated PE is said to be 26%. This figure comes from a trial published in 1960 by Barrit and Jordan^[6] which compared anticoagulation against placebo for the management of PE. Barritt and Jordan performed their study in the Bristol Royal Infirmary in 1957. This study is the only placebo controlled trial ever to examine the place of anticoagulants in the treatment of PR, the results of which were so convincing that the trial has never been repeated as to do so would be considered unethical. That said, the reported mortality rate of 26% in the placebo group is probably an overstatement, given the fact that with the technology of the day, only severe PEs were detected.

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. There is controversy over whether or not small subsegmental PEs need to be treated at all^[7] and there exists some current medical evidence that patients with subsegmental PEs may in fact do quite well without treatment.^[8][9]

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

A notable victim of pulmonary embolism was William II, the last Kaiser of Germany^{[citation needed]}.