Pulmonary embolism

Pulmonary embolism (PE) refers to embolic occlusion of the pulmonary arterial system. The majority of cases result from thrombotic occlusion, and therefore the condition is frequently termed pulmonary thromboembolism, which is what this article mainly covers.

Non-thrombotic pulmonary emboli sources include ³⁰: 

• gas embolism, e.g. air embolism, carbon dioxide embolism, nitrogen, helium

• fat embolism

• tumor embolism: comprised of tumor thrombus

• infectious agents

  • parasitic embolism

  • hydatid embolism

  • septic embolism

• amniotic fluid embolism

• catheter embolism

• brachytherapy seeds

• particulate material embolism, e.g.

  • talc embolism

  • cement embolism: comprised of polymethyl methacrylate (PMMA)

  • iodinated oil embolism

  • metallic pulmonary embolism

    • barium embolism

    • mercury embolism

Terminology

Classification of a pulmonary embolism may be based upon: 

• the presence or absence of hemodynamic compromise

• temporal pattern of occurrence

• the presence or absence of symptoms

• the vessel which is occluded

Clinical presentation

The patient may report a history of recent immobilization or surgery, active malignancy, hormone usage, or a previous episode of thromboembolism. The physical exam may reveal suggestive features such as:

• clinical signs of deep venous thrombosis (DVT)

  • asymmetric pitting lower extremity edema

  • prominent superficial collateral vessels

  • tenderness to palpation along the deep venous system

• tachycardia

• dyspnea

• pleuritic chest pain

• hemoptysis

Clinical decision rules, in conjunction with physician gestalt and estimated pretest probability of disease, may serve as a supplement in risk stratification:

• Wells score

• Geneva score

• PERC rule

ECG

• sinus tachycardia: the most common abnormality

• right heart strain pattern

  • incomplete or complete right bundle branch block

  • prominent R wave in lead V1

  • right axis deviation

  • T-wave inversion in the right precordial leads +/- the inferior leads is seen in up to 34% of patients and is associated with high pulmonary artery pressures ²⁵

• S_IQ_IIIT_III pattern

Pathology

Risk factors

• primary hypercoagulable states

  • protein C deficiency

  • protein S deficiency

  • antithrombin III deficiency

  • lupus anticoagulant

  • factor V Leiden

• recent surgery

• prolonged bed rest/immobility

• malignancy: including multiple myeloma ²³

• HIV ²²:

  • 2-10 x increased risk, cf. non-HIV matched controls

• COVID-19 ²⁷

• medication

  • oral contraceptives

  • thalidomide, lenalidomide ³¹

• pregnancy

• known or previous DVT

• presence of certain venous aneurysms

  • e.g. popliteal venous aneurysm ¹⁵

Markers 

D-dimer (ELISA) is commonly used as a screening test in patients with a low and moderate probability clinical assessment, in these patients:

• normal D-dimer has almost 100% negative predictive value (virtually excludes PE): no further testing is required

• raised D-dimer is seen with PE but has many other causes and is, therefore, non-specific: it indicates the need for further testing if pulmonary embolism is suspected ⁴

In patients with a high probability clinical assessment, a D-dimer test is not helpful because a negative D-dimer result does not exclude pulmonary embolism in more than 15%. Patients are treated with anticoagulants while awaiting the outcome of diagnostic tests ⁴. 

Classification

• hemodynamic

  • massive PE

  • submassive PE

  • low-risk

• temporal pattern

  • acute

  • subacute

  • chronic

• vessel

  • saddle

  • lobar

  • segmental

  • subsegmental

Radiographic features

Depends to some extent on whether it is acute or chronic. Overall, there is a predilection for the lower lobes.

Plain radiograph

Chest radiography is neither sensitive nor specific for a pulmonary embolism. It is used to assess differential diagnostic possibilities such as pneumonia and pneumothorax rather than for the direct diagnosis of PE. 

Described chest radiographic signs include:

• Fleischner sign: enlarged pulmonary artery (20%)

• Hampton hump: peripheral wedge of airspace opacity and implies lung infarction (20%)

• Westermark sign: regional oligemia and highest positive predictive value (10%)

• pleural effusion (35%) - pleural effusions in pulmonary embolism

• knuckle sign ¹¹

• Palla sign ¹⁷: enlarged right descending pulmonary artery

• Chang sign ¹⁸: dilated right descending pulmonary artery with sudden cut-off

Sensitivity and specificity of chest x-ray signs ¹:

• Westermark sign

  • sensitivity ~14%, specificity ~92% , PPV: ~38%, NPV: ~76%

• vascular redistribution

  • sensitivity: ~10% , specificity: ~87% , PPV: ~21%, NPV: ~74%

• Hampton hump

  • sensitivity: ~22% , specificity: ~82%, PPV: ~29%, NPV: ~76%

• pleural effusion

  • sensitivity: ~36% , specificity: ~70%, PPV: ~28%, NPV ~76%

• elevated diaphragm

  • sensitivity: ~20%, specificity: ~85%, PPV: ~30%, NPV: ~76%

CT

Acute pulmonary emboli

CT pulmonary angiography (CTPA) will show filling defects within the pulmonary vasculature with acute pulmonary emboli. When the artery is viewed in its axial plane the central filling defect from the thrombus is surrounded by a thin rim of contrast, which has been called the Polo Mint sign.

Emboli may be occlusive or non-occlusive, the latter is seen with a thin stream of contrast adjacent to the embolus. Typically the embolus makes an acute angle with the vessel, in contrast to chronic emboli. The affected vessel may also enlarge ⁹.

Acute pulmonary thromboemboli can rarely be detected on non-contrast chest CT as intraluminal hyperdensities ¹².

Dual-energy CT holds much promise for the diagnosis and prognosis of PE. Z effective and iodine maps provide lung perfusion assessment. The use of low monoenergetic reconstructions (low monoE) allows 'iodine boosting' of the pulmonary arteries which are useful during suboptimal contrast opacification thereby preventing the need to repeat undiagnostic scans ^ref.

Chronic pulmonary emboli

In contrast to acute pulmonary embolism, chronic thromboemboli are often complete occlusions or non-occlusive filling defects in the periphery of the affected vessel which form obtuse angles with the vessel wall ⁹. The thrombus may be calcified.

Features noted with chronic pulmonary emboli include:

• webs or bands, intimal irregularities ³

• abrupt narrowing or complete obstruction of the pulmonary arteries ³

• “pouching defects” which are defined as chronic thromboembolism organized in a concave shape that “points” toward the vessel lumen ³

Indirect signs include ⁷:

• mosaic perfusion

• vascular calcification

• bronchial or systemic collateralisation

Ultrasound/Echocardiography

Acute pulmonary emboli

Point-of-care ultrasonography is currently not recommended for a haemodynamically stable patient with suspected pulmonary embolism. In the presence of hemodynamic compromise, echocardiography may be of value to assess for the presence of severe right ventricular dysfunction;

• if absent, another cardiopulmonary derangement is likely responsible

• if unequivocally present, it can establish the need for emergent treatment

Echocardiographic features which may be suggestive include:

• thrombus-in-transit

• right ventricular dysfunction

  • commonly dilated and hypocontractile

• flattening or dyskinesis of the interventricular septum

• 60/60 sign

• McConnell sign 

Of note, transesophageal echocardiography has a reported sensitivity of 80.5% and a specificity of 97.2% for ruling in acute pulmonary embolism after the detection of right ventricular overload on transthoracic echocardiography ²⁴. 

Chronic pulmonary emboli

Again not recommended as part of first-line work up. 

Cumulative damage from repeated embolic insults is a common cause of chronic thromboembolic pulmonary hypertension, which demonstrates a variable degree of the aforementioned signs, but with significantly higher right ventricular pressures, right ventricular hypertrophy and diastolic dysfunction, and a higher degree of tricuspid regurgitation. 

MRI

It is difficult to obtain technically adequate images for pulmonary embolism patients using MRI. Magnetic resonance pulmonary angiography (MRPA) should be considered only at centers that routinely perform it well and only for patients for whom standard tests are contraindicated. Technically-adequate magnetic resonance angiography has a sensitivity of 78% and a specificity of 99% ¹³.

Nuclear medicine

A ventilation/perfusion (V/Q) scan will show ventilation-perfusion mismatches. A high probability scan is defined as showing two or more unmatched segmental perfusion defects according to the PIOPED criteria.

Treatment and prognosis

Providing cardiopulmonary support is the initial treatment. Anticoagulation is provided in patients without risk of active bleeding. If the emboli are large or there is a large clot burden, thrombolysis is an option. In some cases, embolectomy or placement of vena cava filters is required.

Anticoagulation treatment for subsegmental pulmonary embolism maybe driven by considerations on recurrence risk, bleeding risk, and patient's preferences ³⁴.

The right ventricular failure due to pressure overload is considered the primary cause of death in severe PE ¹⁴.

Complications

• acute emboli

  • pulseless electrical activity (PEA) in the context of a large obstructing saddle embolus (see mnemonic for causes of PEA)

• acute or chronic emboli

  • right ventricular dysfunction

    • CT features suggestive of right ventricular dysfunction include ⁸:

      • abnormal position of the interventricular septum

      • inferior vena cava contrast reflux

      • RVD (right ventricular diameter): LVD (left ventricular diameter) ratio >1 on reconstructed four-chamber views

        • RVD:LVD ratio >1 on standard axial views is not considered to be a good predictor of right ventricular dysfunction ⁸

    • termed submassive PE when right ventricular dysfunction demonstrated on imaging (CT or echo) but without clinical hemodynamic compromise ¹⁹

• subacute-to-chronic emboli

  • pulmonary infarction

  • pulmonary hypertension

  • pulmonary arterial sclerosis

• chronic emboli

  • cor pulmonale

Resolution over time

Around 80% of emboli resolve at approximately 30 days ^20,21. Residual pulmonary obstruction at 6 months after the first episode was shown to be an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension ²⁸.

History and etymology

It was first reported In the1850s, by the German physician and pathologist Rudolf Virchow ³³.

Differential diagnosis

• artifacts

  • pulmonary artery flow artifact

  • contrast-blood level - due to slow flow

  • breathing motion

  • beam hardening

    • hyperconcentrated contrast in the superior vena cava

    • medical devices e.g. catheters, orthopedic prostheses

    • patient's arms in a down position

  • patient movement

  • transient contrast bolus interruption ¹⁶, due to Valsalva or a patent foramen ovale, causing non-opacified blood to enter the right ventricle and pulmonary arteries (scanning in end-expiration can reduce or eliminate this artifact)

• iatrogenic

  • cavopulmonary anastomosis

• neoplastic

  • pulmonary artery sarcoma

• inflammatory

  • pulmonary artery vasculitis e.g. Takayasu arteritis

• interpretational

  • misidentification of pulmonary veins for arteries

  • arterial bifurcations (or branch points) - usually easily distinguished on multiplanar assessment

  • chronic emboli may be mistaken for acute emboli 

  • thromboembolic emboli may be mistaken for other embolized material

See also

• pulmonary embolism rule-out criteria (PERC)

• Wells criteria for pulmonary embolism

• Geneva score

• YEARS criteria for pulmonary embolism