Pulmonary embolism (PE) is a fatal clinical condition that occurs as a result of mechanical obstruction of the pulmonary artery or its branches by any material (such as thrombus, air or fat) from anywhere in the body. Pulmonary embolism can be an acute condition in which the signs and symptoms develop immediately after the event (i.e the obstruction of the pulmonary vessels), or it can be chronic in which the signs and the symptoms develop progressively over years. In this article, you will be able to understand the definition, incidence, pathophysiology, risk factors, symptoms and signs, and the prognosis of the pulmonary embolism.
pulmonary embolism

Image: “A large pulmonary embolism at the bifurcation of the pulmonary artery (saddle embolism).” by James Heilman, MD. License: CC BY-SA 3.0

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Definition of PE

Pulmonary embolism — mechanical obstruction of the pulmonary vessels

Pulmonary embolism (PE), is defined as a serious disease which results from obstruction of the pulmonary vessels mechanically by a thrombus, air, fat or tumor elsewhere in the body, a process called embolization. PE can be classified into massive or submassive pulmonary embolism.

Epidemiology of PE

Incidence of pulmonary embolism

A study on more than 42 million deaths during 20 years have shown that only about 1.5 % (600.000) was diagnosed with pulmonary embolism. 200.000 deaths were assumed to be as a result of PE. Although these are large numbers, they still underestimate the true incidence of pulmonary embolism since more than half of patients pass undiagnosed. More cases have been diagnosed over the past few years after the introduction of the gold standard modality in diagnosis of PE, which is the CT-pulmonary angiography.

Classification of PE

Pulmonary embolism is classified into either massive pulmonary embolism or submassive pulmonary embolism.

Massive pulmonary embolism

Massive PE causes severe lowering of blood pressure (hypotension) and should be suspected in any patient presenting with hypotension associated with jugular venous distention, that is not fully explained by any other underlying disease, such as acute MI, pericardial tamponade, tension pneumothorax, or new arrhythmia. Criteria of diagnosis are:

  • Systolic BP < 90 mmHg or a drop in systolic BP of ≥ 40 mmHg from the patient’s baseline blood pressure.
  • Hypotension should persist for a period more than 15 minutes.

The prognosis of massive pulmonary embolism is very bad and usually results in right ventricular dysfunction and death.

Submassive pulmonary embolism

If acute PE doesn’t meet the criteria of massive PE, then it’s considered submassive pulmonary embolism.

Pathophysiology of PE

Deep vein thrombosis of the right leg

Image: “A deep vein thrombosis of the right leg. Note the swelling and redness.” by James Heilman, MD. License: CC BY-SA 3.0

The process of embolization arises from underlying thrombi that formed elsewhere in the body. Thrombi arise commonly from the deep venous system of the lower extremities as in deep venous thrombosis (DVT), therefore assessment of the lower extremities deep veins by duplex is important to rule out DVT especially in bedridden patients because they are at risk of blood stagnation and formation of thrombi. Although lower limbs DVT is the most common cause of pulmonary embolism, thrombi may also originate from right side of the heart, upper extremities, pelvic or renal veins.

Most clinically recognized PE results from dislodged thrombi in the Iliofemoral veins. About 60–80 % of iliac, femoral and popliteal vein thrombi arise below the popliteal vein (Calf vein thrombi), then propagate proximally, while the rest of the thrombi arise from the proximal veins themselves. Upper extremity venous thrombosis became a very common problem after increased usage of central venous catheters, insertion of permanent pacemakers and internal cardiac defibrillators (ICD).

The problem starts when these thrombi dislodge from their sites of formation and spread to the lungs through the right side of the heart with subsequent lodging of the large thrombi at the bifurcation of the main pulmonary artery or their branches causing hemodynamic instability.

Sometimes an embolus may pass paradoxically through a congenital shunt between right and left atrium (e.g patent formen ovale) into the arterial circulation causing acute lower limb ischemia. Sometime smaller thrombi travel more distally into the smaller pulmonary branches, then initiates inflammatory reactions adjacent to the parietal plura causing pleuritic chest pain. 10 % of patients especially those with underlying cardiopulmonary disease are at risk of pulmonary infarction. Pulmonary emboli are usually large in number, and lodge more commonly in the lower lobes of the lungs in the majority of cases.

Pathophysiological abnormalities in pulmonary embolism (PE)

  • Obstruction of the pulmonary vessels and secreting vasoactive agents from the platelets result in pulmonary vasoconstriction and increased pulmonary vascular resistance. This pathophysiological can cause ventilation-perfusion mismatching at remote sites from the emboli.
  • Impairment of gas exchange caused by:
    1. An increase in the alveolar dead space which occurs as result of vascular obstruction by the emboli.
    2. Hypoventilation of alveoli relative to alveolar perfusion in the non-obstructed lung.
    3. Right-to-left shunting
    4. Impairment of carbon monoxide transfer because of loss the gas exchange surface.
  • Reflex stimulation of irritant receptors in the lungs may result in alveolar hyperventilation.
  • Increased resistance of the airway due to constriction of the airways distal to the lungs bronchi.
  • Decreased pulmonary compliance as a result of:
    1. Loss of surfactant
    2. Lung edema
    3. Lung hemo

Right ventricular (RV) dysfunction

Pulmonary embolism usually causes RV dysfunction and progressive right side heart failure due to increased pulmonary vascular resistance and the right ventricular (RV) wall tension, resulting in further RV dilatation and dysfunction.

Risk Factors of PE

The most common risk factor of pulmonary embolism is deep venous thrombosis (DVT) which accounts in about 50 % of PE cases. This indicates that the risk factor of DVT is the same for pulmonary embolism. The other risk factors account for the rest 50 % of cases, and include:

  • Immobilization
  • Surgery within the last 3 months
  • Stroke
  • Paresis
  • Paralysis
  • Central venous instrumentation within the last 3 months
  • Malignancy
  • Chronic heart disease
  • Autoimmune diseases
  • History of venous thromboembolism
  • Risk factors in women include obesity (BMI ≥ 29 kg/m2), heavy cigarette smoking (> 25 cigarettes per day), and hypertension.

Symptoms of PE

Signs of pulmonary embolism

Symptoms and signs of PE are not specific and clinicians can’t depend on them to confirm or exclude pulmonary embolism, as they can occur in a patient without pulmonary embolism. Occult pulmonary embolism is hardly diagnosed in presence of concomitant heart failure or pneumonia, in such conditions, patients usually fail to respond to the standard medical treatment of the concomitant condition.

Most common symptoms of pulmonary embolism are:

  1. Dyspnea at rest or with exertion, which starts suddenly within seconds or minutes
  2. Pleuritic pain
  3. Cough
  4. Orthopnea
  5. Calf pain
  6. Swelling of the calf or thigh
  7. Wheezing

Most common signs of pulmonary embolism are:

  1. Tachypnea
  2. Tachycardia
  3. Rales
  4. Decreased breath sounds
  5. Accentuated pulmonic component of the 2nd heart sound (P2)
  6. Jugular venous distension

Massive pulmonary embolism can be associated with RV dysfunction, which manifests as:

  1. An increased in jugular venous pressure
  2. Right-sided S3 heart sound
  3. Parasternal heave

As deep venous thrombosis (DVT) is the most common cause of PE, symptoms and signs of DVT have been found in more than 57 % of cases of pulmoney embolism (PE), which include erythema, edema, tenderness, or a palpable cord in the calf or thigh.

Clinicians should realize that PE is very frequently asymptomatic especially if it’s submassive PE which can manifest as oxygen desaturation without concomitant symptoms or signs suggestive of pulmonary embolism.

Investigations of PE

As symptoms and signs of pulmonary embolism are variable and not specific, additional diagnostic tests are important to help you in diagnosing the PE.

Non-imaging diagnostic modalities

Laboratory tests

Routine lab tests (not specific)
  1. Leukocytosis
  2. Increased erythrocyte sedimentation rate (ESR)
  3. High serum LDH or AST with a normal serum bilirubin
Arterial blood gas (ABG) Arterial blood gas (ABG) usually reveal:

  1. Hypoxemia
  2. Hypocapnia
  3. Respiratory alkalosis

These typical ABG findings are not frequently seen, as:

  1. Massive PE with circulatory collapse and hypotension can cause hypercapnia with a combined respiratory acidosis and metabolic acidosis (high lactic acid).
  2. Hypoxemia can be absent or minimal.
  3. 18 % of patients has PO2 between 85–105 mmHg.
Brain natriuretic peptide (BNP)
  • Levels of BNP can be greater in patients of PE.
  • It’s insensitive test, as it is not elevated in some patients with pulmonary embolism.
  • It’s non-specific test, as it can be elevated by other causes.
  • Sensitivity and specificity of BNP is only 60 %
Troponin Troponin I and T can be elevated in 50 % of patients that have large PE, and usually resolve rapidly 40 hours in patients with PE, in contrast to the longer duration in patients with myocardial infarction.
  • It’s a product of degradation of cross-linked fibrin.
  • It has good sensitivity and -ve predictive value, and poor specificity and +ve predictive value (i.e. good negative test).
  • If quantitative assays are used, a level > 500 ng/mL is considered abnormal.
  • If D-Dimer level is < 500 ng/ml using quantitative ELISA or semi-quantitative latex agglutination → It excludes PE in patients with low or moderate pretest probability of PE.

Electrocardiography (ECG)

ECG changes can be seen in normal person without PE, limiting the role of ECG in diagnosis of PE. The characteristic ECG abnormalities that commonly seen in massive PE and cor-pulmonale are:

  • S1Q3T3 pattern
  • Right ventricular strain → T-wave inversion in chest leads may indicate severe RV dysfunction
  • New incomplete right bundle branch block

Some ECG changes may indicate poor prognosis, such as:

  1. Atrial arrhythmias
  2. Right bundle branch block
  3. Inferior Q-waves
  4. Precordial T-wave inversion and ST-segment changes

Non-Invasive imaging modalities

Chest CT with contrast (CT pulmonary angiography)

Chest CT with contrast is an important non-invasive imaging modality used to diagnose PE, and now is considered the gold standard investigations of PE and has largely replaced the invasive modalities. CT chest also provides very good images to the both ventricles of the heart. RV enlargement may indicate a more risk of death within the next 30 days when compared with a patient with PE without RV enlargement.

Ventilation/perfusion scan (V/Q scan)

Segmental and subsegmental pulmonary emoboli on both sides

Image: “Segmental and subsegmental pulmonary emoboli on both sides” by James Heilman, MD. License: CC BY-SA 4.0

Lung scan is considered the second-line diagnostic modality for patients with pulmonary embolism who can’t tolerate IV contrast due to risk of contrast-induced nephropathy. The diagnosis involves intravenous administration of albumin labeled with a gamma-emitting radionuclide which them get trapped in the pulmonary capillary bed.

  • Perfusion scan: Perfusion defect indicates decreased or absent pulmonary blood flow.
  • Ventilation scan: Abnormal ventilation indicate non-ventilated areas in the lungs.

High-probability V/Q scan is defined as presence of two or more segmental perfusion defects with normal ventilation.


Echocardiographic findings suggestive of pulmonary embolism is seen only in 30–40 % of patients especially in massive PE, and include:

  • Increased right ventricular (RV) size
  • Decreased RV function
  • Tricuspid regurgitation
  • RV thrombus
  • McConnell’s sign: Regional wall motion abnormalities which spare the apex of RV

Venous ultrasonography

Normal veins are compressible with gentle pressure using the ultrasound transducer. Loss of the normal compressibility of the vein due to destination of the vein by the acute thrombus is considered the primary criterion for diagnosis of DVT. The diagnosis of DVT can be confirmed largely by visualization of the homogeneous thrombus. Presence of DVT suggests largely diagnosis of pulmonary embolism, and patient should receive the treatment of PE.

Chest radiography

Radiographic changes in patients with pulmonary embolism are anot specific, and can be seen in someone without PE, and include:

  • Atelectasis or pulmonary parenchymal abnormality
  • Pleural effusion
  • Cardiomegaly

Invasive imaging modalities

pulmonary angiography

Image: “CT pulmonary angiography images confirming the presence of a saddle embolus and substantial thrombus burden in the lobar branches of both main pulmonary arteries” by Aung Myat and Arif Ahsan. License: CC BY 2.0

Pulmonary angiography

This invasive modality involves percutaneous catheterization of pulmonary artery or one of its branches usually via the femoral vein and then injecting the contrast to delineate the pulmonary vasculature. Although It is considered the definitive diagnostic modality of pulmonary embolism, it has been replaced largely with spiral CT chest with contrast. It’s now only reserved for two situations:

  1. If diagnosis of PE is not successful using CT scan
  2. If patient is going to have catheter-used thrombolysis or embolectomy

Diagnosis of PE

There are score methods useful in estimating the patient likelihood of DVT and pulmonary embolism (PE):

  • Score is zero or less → Low clinical likelihood of DVT
  • 1 to 2 → Moderate likelihood
  • 3 or greater → High likelihood
Clinical variable Score
Active cancer 1
Paralysis, paresis, or recent cast 1
Bedridden for > 3 days; major surgery < 12 weeks 1
Tenderness along distribution of deep veins 1
Entire leg swelling 1
Unilateral calf swelling > 3 cm 1
Pitting edema 1
Collateral superficial nonvaricose veins 1
Alternative diagnosis at least as likely as DVT –2
High clinical likelihood of PE if point score exceeds 4
Major criteria Score
Signs and symptoms of DVT 3.0
Alternative diagnosis less likely than PE 3.0
Heart rate > 100/min 1.5
Immobilization > 3 days; surgery within 4 weeks 1.5
Prior PE or DVT 1.5
Hemoptysis 1.0
Cancer 1.0

Treatment of PE


If pulmonary embolism was suspected in any patient, clinicians should focus first on stabilizing the patient, which requires:

Respiratory support

Patient should receive high-flow oxygen (about 60–100 %) if hypoxemia is present. Severe hypoxemia and respiratory failure may require intubation and mechanical ventilation.

Hemodynamic support

Hemodynamic support should be provided to a patient with massive PE and hypotension with systolic blood pressure < 90 mmHg or drop in the systolic BP more than or equal 40 mmHg from patient’s baseline. Hemodynamic support involves:

  1. IV fluid administration is considered the first line of treatment.
  2. If patient’s hemodynamic state is not improved with fluids, then IV vasopressor therapy should be considered, such as norepinephrine, dopamine, dobutamine or epinephrine.

Empirical anticoagulant

If clinician suspects a pulmonary embolism, empirical anticoagulation using subcutaneous low-molecular-weight heparin is indicated providing no excess risk for bleeding.


Anti-coagulation therapy

If further evaluation of a suspected patient excludes the presence of PE, then empirical anticoagulation should be discontinued, and alternate diagnosis should be considered.

If further evaluation of a suspected patient confirmed the presence of PE, then initiate anticoagulant treatment or continue it if it has been already begun empirically. Clinicians can use subcutaneous low molecular weight heparin (LMWH) easily without monitoring of PTT, or can use unfractionated heparin (UH) with target PTT 50–70 . LMWH heparin should be given for at least 5 days as a bridge, during which oral warfarin is given concomitantly. Stop the LMWH heparin when patient’s INR is target is reached ( 2–3 ).

Duration of oral anticoagulation:

  • Patient with persistent risk factors, or history of previous PE, should be given oral anticoagulant for life to avoid further events.
  • Patients with reversible and identifiable risk factors should be given oral anti-coagulant for 3 months only.
  • Anti-coagulation for a period of 6 months is recommended if the condition is idiopathic or the risk factors are week.

Fibrinolytic therapy

Thrombolytic therapy such as streptokinase will remove the pulmonary emboli rapidly and provides survival benefit in massive pulmonary embolism. It’s indicated in:

  1. Hemodynamically unstable patient with massive PE
  2. Hemodynamically stable patient with adverse outcomes such as RV dysfunction

Inferior vena caval (IVC) filters

IVC filters provide a guard barrier in the inferior vena cava preventing the large emboli from passing to the lungs. Placement of IVC filters is generally indicated if:

  1. Contraindications to anticoagulation
  2. Failed anticoagulation
  3. Patient developed complications due to anticoagulation


Embolectomy means removal of the emboli, which can be done using a catheter directed to the involved pulmonary branch or surgically. It’s indicated when the patient has massive PE with hemodynamically instability where the thrombolytic therapy failed or contraindicated.

Prognosis of PE

Patients who had a previous PE carry high risk for further events in the future, especially if there are associated persistent risk factors. The highest risk of recurrence is the first 6 to 12 months after the previous event, and about one-third of patients will suffer from new event of PE if risk factors are persistent. The risk of recurrence is low in patients with reversible or temporary risk factors.

The mortality rate is highest in patients with echocardiographic findings of RV dysfunction or cardiogenic shock. Most people with RV dysfunction will attain normal RV function by 3 weeks, and persistent pulmonary hypertension (PHTN) may exist in about 5 % of patients by two years. A few patients may progress into overt RV failure and develop signs and symptoms of Right-side heart failure.

Review Questions

The correct answers can be found below the references.

1. A 59 year old male patient, smoker and hypertensive, recently had total hip replacement. 3 days post-operative, the patient started to complain of unexplained acute shortness of breath, tachypnea and drowsiness. His blood pressure was 90/60 and his heart rate: 120 beats/ minutes, ECG was done and showed Rt. axis deviation with ST depression and T-wave inversion in V1-V3. The patient is suspected to have massive pulmonary embolism. The gold standard diagnostic test to confirm diagnosis of pulmonary embolism is…

  1. …CT pulmonary angiography.
  2. …echocardiography
  3. …elevated D-Dimer test.
  4. …chest x-ray.

2. A 60 year old male patient presented with confirmed pulmonary embolism, the risk factors were identified and reversible. The duration of anti-coagulation for this patient to prevent further similar events is…

  1. …anti-coagulation for life.
  2. …anti-coagulation for 6 months.
  3. …anti-coagulation for 3 months.
  4. …anti-coagulation for 12 months.

3. This most common risk factor for pulmonary embolism in which its diagnosis would confirm diagnosis of PE is…

  1. …deep venous thrombosis (DVT).
  2. …continuous immobilization.
  3. …recent surgery within the last 3 months.
  4. …history of malignancy.
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