Pulmonary Embolism

Overview

An embolism is a free-floating mass in the blood that can lead to the occlusion of blood vessels and can be a blood clot (thrombus), fat (fat embolism), gas, amnionic fluid, or other material. A pulmonary embolism (PE) is the blockage of a pulmonary artery by a mass that has originated somewhere else in the body. A PE is a medical emergency.

Venous thromboembolism (VTE) is an umbrella term for deep vein thrombosis (DVT) and PE.

Epidemiology

• Incidence is estimated to be around 70 per 100,000 people
• VTE is the third most common cardiovascular disease after myocardial infarction and stroke

Risk Factors

• Up to 30-50% have no identifiable cause (unprovoked)
• Deep vein thrombosis (DVT)
• Previous VTE
• Active cancer
• Recent surgery (within the last 2 months), especially major orthopaedic surgery
• Significant immobility (e.g. hospitalisation or bed rest >5 days)
• Lower limb paralysis, trauma, or fracture
• Pregnancy and the postpartum period
• >60 years of age
• Combined oral contraceptive use
• Obesity
• Long-distance sedentary travel (e.g. long-haul flights)
• Varicose veins
• Superficial venous thrombosis
• Any cause of hypercoagulable state (e.g. factor V Leiden, antiphospholipid syndrome)
• Behçet’s disease
• Nephrotic syndrome (due to loss of antithrombin III and plasminogen in urine)

Presentation

There is a classic triad of dyspnoea, haemoptysis, and pleuritic chest pain, however in reality this only presents in around 10% of patients. Any patient with sudden-onset shortness of breath should raise suspicion of a PE. Features may be:

• Dyspnoea – most common presenting complaint (usually acute)
• Pleuritic chest pain (usually acute)
  • This is usually localised to one side of the chest
• Tachycardia
• Tachypnoea
• Signs of a DVT:
  • Usually pain and swelling in one leg (or both), and there may be redness, warmth, and distended veins
• Presence of risk factors in the history
• Cough
• Fever
• Haemoptysis – present in around 8% of patients

Haemodynamic instability suggests a massive pulmonary embolism and usually requires critical care. Features may be:

• Tachycardia
• Hypotension
• Acute right ventricular dysfunction (e.g. elevated jugular venous pressure)
• Syncope or pre-syncope

Differential Diagnoses

Acute pericarditis

• Although the chest pain is also pleuritic, it is usually central and relieved when sitting up and worse lying down
• An ECG may show electrical alternans and widespread saddle-shaped ST elevation and PR depression
• D-dimer is normal

Pneumonia

• There is usually a cough productive of purulent sputum
• The fever is generally higher than in a PE
• Chest X-rays may show opacity
• The onset is usually not sudden

Unstable angina or myocardial infarction

• Chest pain is usually described as retrosternal heaviness radiating to the jaw, arm, or neck
• Can be difficult to distinguish based on signs and symptoms below
• ECG changes suggestive of myocardial ischaemia are usually present

Costochondritis

• The onset of pain is insidious and usually located around the anterior chest wall
• The pain is worsened by certain chest movements and deep inspiration
• There may be point tenderness
• They may be difficult to distinguish clinically

Assessment

Pulmonary embolism rule-out criteria (PERC)

The PERC rule can be used to rule out a PE when the suspicion of diagnosis is relatively low, but reassurance is desired. The PERC is negative when none of the criteria are present, making the probability of a PE is <2%. A score >0 (i.e. if any feature is present) is a positive PERC.

If the suspicion of a PE is higher, the PERC should be skipped and a 2-level PE Wells score should be calculated.

Table 1: Table 1: The pulmonary embolism rule-out criteria (PERC)

Two-level PE Wells score

If a PE is suspected, then a Two-level PE Wells score should be calculated. A PE is likely if there are >4 points and unlikely if there ≤4 points.

Investigations

All patients

• Chest x-ray:
  • Should be offered to all patients, usually normal
• ECG:
  • Sinus tachycardia is most commonly seen
  • In around 20% of patients, the ‘S1Q3T3’ sign may be seen

PE likely (>4 points on two-level PE Wells score)

• Immediate CT pulmonary angiogram (CTPA):
  • If there is a delay in performing a CTPA, give interim anticoagulation
    • If CTPA positive: continue anticoagulation
    • If CTPA is negative: consider proximal leg vein ultrasound if DVT suspected
  • If the patient has renal impairment: use V/Q scan instead of CTPA (this is because a CTPA uses contrast)

PE unlikely (≤4 points on two-level PE Wells score)

• Immediate D-dimer test:
  • If D-dimer positive: arrange CTPA (or V/Q scan if renal impairment present)
    • If there is a delay in performing CTPA, give interim anticoagulation
  • If D-dimer negative: stop anticoagulation and consider an alternate diagnosis

Pathway

A flowchart of the above steps is as follows:

Management

All patients

• 1^st-line: use Pulmonary Embolism Severity Index (PESI) score to determine whether inpatient or outpatient treatment is required based on their risk + treat according to the options below
  • Patients with haemodynamic instability, other comorbidities, a lack of support at home, or difficulties with adhering to medication, should be treated as inpatients
• Management is effectively the same as a DVT.

Non-pregnant patients without renal dysfunction

• 1^st-line: direct oral anticoagulant (DOAC) such as apixaban or rivaroxaban
  • If both apixaban and rivaroxaban unsuitable then either:
    • Low molecular weight heparin (LMWH) followed by dabigatran or edoxaban
    • LMWH followed by warfarin
• If the patient has cancer: use DOAC and follow above steps
• If the patient has antiphospholipid syndrome: LMWH followed by lifelong warfarin

Severe renal dysfunction (eGFR <15 /min)

• 1^st-line: LMWH, unfractionated heparin, or LMWH followed by warfarin

Pregnant patients

• 1^st-line: subcutaneous LMWH or IV heparin
• Warfarin is contraindicated in pregnancy
• DOACs are not used in pregnancy as there is no information surrounding their use

PE with haemodynamic instability

These are patients with massive PE and haemodynamic instability (i.e. hypotension)

• 1^st-line: thrombolysis

Length of anticoagulation in all patients

• If the DVT was provoked (there was an obvious event causing it e.g. prolonged immobilisation): continue anticoagulation for 3 months
• If the DVT was unprovoked: continue for 6 months
• If the patient has active cancer: continue for 6 months

Monitoring

• If warfarin is used, the INR target is 2.5, keeping in the range of 2.0 – 3.0
• Consider basic investigations for cancer in patients who have had an unprovoked DVT:
  • Review medical history and blood test results including FBC, U&Es, LFTs, PT, and APTT, and offer a physical examination
  • Do not offer further investigations for cancer unless the patient has relevant clinical signs or symptoms
• Consider thrombophilia testing once anticoagulation has stopped in patients with an unprovoked DVT:
  • Consider testing for antiphospholipid syndrome
  • Hereditary thrombophilias in people who have a family history of a DVT or PE

Patient Advice

• Patients should be advised on the length of duration and the importance of adherence
• If patients are taking warfarin, advise on monitoring and interactions 
• DOACs do not need routine monitoring
• Patients should be safety-netted on the signs and symptoms of a DVT and PE and should be instructed to seek immediate help should they arise.

Complications

• Pulmonary infarction
• Chronic thromboembolic pulmonary hypertension
• Cardiac arrest
• Death

Prognosis

• PE is the leading cause of pregnancy-related maternal death in developed countries
• If left untreated, the prognosis is poor with a high mortality rate
• The mortality rate is higher in those who are haemodynamically unstable or go into cardiac arrest