Pulmonary Embolism

• Pulmonary embolism (PE) refers to the obstruction of one or more branches of the pulmonary artery by material—most commonly a thrombus—that has migrated from another site within the body, typically the deep venous system of the lower extremities. Less commonly, the embolic material may consist of air, fat, or tumour cells
• PE is predominantly a consequence of deep vein thrombosis (DVT). Thrombi most often form in the deep veins of the legs, particularly around venous valve pockets where stasis promotes clot formation. Once formed, a thrombus may dislodge, pass through the right heart chambers, and become lodged in the pulmonary arterial tree.
• Venous thromboembolism (VTE) encompasses the entire spectrum from initial thrombus formation driven by Virchow's triad—venous stasis, endothelial injury, and hypercoagulability—to DVT and its most serious complication, PE.
• PE is not considered a disease in isolation, but rather a complication of venous thrombosis. It represents the culmination of pathogenic processes occurring within the venous system and manifests when a thrombus obstructs pulmonary circulation.
• Anatomically, emboli may be:
  • Saddle emboli, situated at the bifurcation of the main pulmonary artery;
  • Main, lobar, segmental, or subsegmental based on the extent and location within the pulmonary arterial tree;
  • Clot-in-transit, where the embolus is visualised passing through the right heart before occlusion.
• The anatomical site influences clinical presentation. Proximal emboli are more likely to cause haemodynamic instability, whereas distal emboli are associated with pulmonary infarction and pleuritic pain.
• Classification by clinical severity is based on the risk of death and not merely on anatomical location:
  • High-risk PE involves haemodynamic instability, often with systolic blood pressure <90 mmHg or the need for vasopressors.
  • Intermediate-risk PE includes normotensive patients with right ventricular dysfunction or myocardial injury.
  • Low-risk PE refers to patients who are haemodynamically stable with no evidence of right heart strain or elevated cardiac biomarkers.
• Approximately 51% of deep venous thrombi embolise to the pulmonary circulation, indicating that PE is a frequent and clinically significant consequence of DVT.

Virchow’s Triad

• The fundamental model explaining the pathogenesis of venous thromboembolism (VTE), including PE, is Virchow’s triad, consisting of:
  • Venous stasis: Impaired or stagnant blood flow promotes thrombus formation.
  • Endothelial injury: Damage to the vessel wall, especially at venous valves, triggers thrombogenesis.
  • Hypercoagulability: A predisposition to thrombus formation due to acquired or inherited prothrombotic states.
• These three elements interact to initiate clot formation, with thrombi typically forming as a platelet and fibrin nidus that grows into a red fibrin-rich thrombus. This thrombus may become incorporated into the venous wall or embolise to the pulmonary circulation.

Thrombus Origin and Embolisation

• Most emboli originate in the deep venous system of the lower extremities, especially the calf veins.
• Less commonly, thrombi may form in the pelvic, renal, or upper extremity veins, or within the right heart chambers.
• Larger thrombi may lodge at the pulmonary artery bifurcation or within lobar branches, potentially leading to haemodynamic instability.
• Smaller thrombi tend to occlude peripheral arteries and are more likely to cause pleuritic chest pain via local inflammation adjacent to the pleura.

Key Aetiological Factors

Venous Stasis

• Prolonged immobility (e.g., bed rest >3 days, long-distance travel >4 hours).
• Advanced age, particularly >40 years.
• Congestive heart failure, obesity, or paralysis.
• Conditions causing external venous compression (e.g., tumours).
• Postoperative states (especially after orthopaedic or pelvic surgery).
• Hospitalisation with restricted mobility, particularly for cardiac or pulmonary conditions.

Endothelial Injury

• Surgical trauma, especially involving vein harvesting or catheter placement.
• Prior history of DVT.
• Central venous catheterisation.
• Mechanical injury from fractures or direct trauma.

Hypercoagulability

Acquired Conditions

• Malignancy: Especially with pancreatic, gastric, lung, brain, or haematological cancers. Chemotherapy and indwelling lines further increase risk.
• Pregnancy and postpartum period: Risk peaks in the first six weeks postpartum.
• Oestrogen exposure: Combined oral contraceptives or hormone replacement therapy increase thrombotic risk, especially with higher oestrogen content.
• Nephrotic syndrome: Due to urinary losses of anticoagulant proteins.
• Inflammatory conditions: Including inflammatory bowel disease and systemic lupus erythematosus.
• Sepsis or recent infections: Pneumonia, urinary tract infections, and HIV are known triggers.
• Acute cardiovascular events: Myocardial infarction and heart failure.
• Blood transfusions and polycythaemia: Elevate blood viscosity.
• Drug-related risks: Heparin-induced thrombocytopenia, phenothiazines, and IV drug use.
• Sleep-disordered breathing and obesity: Associated with systemic inflammation and hypoxia-induced coagulopathy.

Inherited Conditions (Thrombophilia)

• Factor V Leiden mutation: Most common cause of familial thrombophilia; confers resistance to activated protein C.
• Prothrombin G20210A mutation: Elevates plasma prothrombin levels and thrombotic risk.
• Antithrombin III deficiency
• Protein C or S deficiency
• Antiphospholipid antibody syndrome
• Other rare abnormalities: Plasminogen, fibrinogen, or plasminogen activator deficiencies.
• Inherited thrombophilias are particularly significant in younger patients with unprovoked PE or a family history of thrombosis.

Paediatric Considerations

• In children, PE is almost always associated with an identifiable risk factor.
• Central venous catheters are the most common cause, especially in neonates and children receiving long-term parenteral nutrition.
• Other factors include inherited thrombophilias, hyperhomocysteinaemia, and antiphospholipid antibodies.
• In critically ill infants, dehydration and hyperosmolar states further contribute to risk.

Cumulative Risk and PIOPED II Findings

• The PIOPED II study found that 94% of adults with PE had at least one major risk factor:
  • Immobilisation
  • Surgery within the previous three months
  • Malignancy
  • Prior history of DVT or PE
  • Recent trauma
  • Smoking
  • Central venous instrumentation
  • Stroke or paresis
  • Heart failure or chronic pulmonary disease
  • Recent infection or hormonal therapy

Multifactorial Nature

• In many patients, no single cause is sufficient to explain thrombus formation. Instead, the interaction of several mild risk factors may combine to produce a prothrombotic state.

Initial Event: Embolisation and Vascular Obstruction

• Pulmonary embolism occurs when a thrombus dislodges—most often from the deep veins of the lower extremities—and becomes lodged in the pulmonary arterial circulation.
• The emboli are typically multiple and more commonly involve the lower lobes of the lungs; bilateral involvement is frequent.
• Larger emboli may obstruct the main pulmonary artery or its bifurcation, leading to saddle embolus, which can severely impair cardiovascular function. Smaller emboli tend to lodge in segmental or subsegmental branches, potentially causing pulmonary infarction and haemorrhage.

Haemodynamic Consequences

• Obstruction of the pulmonary vasculature by emboli causes an acute increase in pulmonary vascular resistance (PVR) due to:
  • Mechanical blockage of blood flow.
  • Reflex hypoxic pulmonary vasoconstriction.
  • Release of vasoconstrictors such as serotonin.
• When more than 30–50% of the pulmonary arterial cross-sectional area is occluded, pulmonary artery pressures rise significantly.
• The right ventricle (RV) faces an abrupt increase in afterload. To compensate, it dilates and increases contractility through the Frank-Starling mechanism.
• As RV pressures escalate, the interventricular septum bows toward the left ventricle (LV), impairing LV filling and output. The result is systemic hypotension and, in severe cases, obstructive shock.
• In individuals with pre-existing cardiopulmonary disease, even smaller emboli may cause profound haemodynamic instability due to impaired RV reserve.

Gas Exchange Impairment

• PE disrupts normal ventilation-perfusion (V/Q) matching:
  • Perfusion is lost in obstructed areas while ventilation remains preserved, leading to dead space ventilation and inefficient gas exchange.
  • Redistribution of blood to unobstructed regions causes overperfusion there, resulting in low V/Q ratios and hypoxaemia.
  • Hypoxaemia may also be worsened by intrapulmonary shunting, atelectasis due to surfactant dysfunction, or low mixed venous oxygen levels secondary to reduced cardiac output.
• Hyperventilation, driven by hypoxaemia and inflammatory signals, often leads to hypocapnia and respiratory alkalosis.
• Hypercapnia is rare but may occur in cases of circulatory shock due to decreased minute ventilation and impaired gas exchange.

Pulmonary Infarction

• Pulmonary infarction occurs in approximately 10% of PE cases and is more common when segmental or subsegmental arteries are occluded.
• It is characterised histologically by intra-alveolar haemorrhage and necrosis of lung parenchyma.
• The classic clinical triad includes pleuritic chest pain, haemoptysis, and pleural effusion.
• Although historically thought to occur more frequently in individuals with underlying cardiac disease, more recent data suggest that younger patients without cardiopulmonary comorbidities are at higher risk, likely due to less developed bronchial collateral circulation.
• The lung’s oxygen supply derives from pulmonary arteries, bronchial arteries, and alveolar oxygen diffusion. Infarction results when these sources are insufficient, most commonly affecting the right lower lobe due to gravity-dependent perfusion dynamics.

Inflammatory and Reflex Responses

• Thromboembolism induces a cascade of inflammatory responses:
  • Release of cytokines and vasoactive substances (e.g., serotonin, histamine).
  • Local bronchoconstriction and vasoconstriction further reduce effective pulmonary perfusion.
  • Inflammatory damage may impair surfactant production, precipitating atelectasis.
• These processes contribute not only to gas exchange abnormalities but also to the sensation of dyspnoea and stimulation of the respiratory drive.

Cardiovascular Collapse and Death

• In massive PE, rapid RV failure is the leading cause of death. If RV systolic pressure exceeds its capacity—often needing to surpass 50 mmHg to maintain pulmonary blood flow—circulatory collapse may ensue.
• Hypotension results from decreased LV preload, secondary to reduced RV output and septal shift, culminating in shock and multi-organ hypoperfusion.
• Early recognition of right heart strain, hypotension, and signs of shock is critical, as these are the strongest indicators of early (in-hospital or 30-day) mortality.

General Incidence and Trends

• The annual incidence of pulmonary embolism in the general population is approximately 1 case per 1,000 persons, though reported rates have increased over time due in part to broader use of computed tomography pulmonary angiography (CTPA).
• In the United States, hospital data suggest 650,000–900,000 venous thromboembolic (VTE) events annually, encompassing both fatal and non-fatal cases. Autopsy studies reveal that 60% of hospital deaths involve undiagnosed PE.
• From 1979 to 1998, age-adjusted PE mortality in the US declined from 191 to 94 deaths per million, yet subsequent regional studies found either a plateau or only minimal further decline.
• Between 2007 and 2009, there were 277,549 adult PE-related hospitalisations annually, with a mean of 19,297 deaths per year. The hospitalisation rate was 121 per 100,000 population.
• Between 1993 and 2012, hospital data in the US revealed an increase in PE admissions from 23 to 65 per 100,000, with a modest rise in massive PE and related mortality.

Global Variation

• Incidence differs globally, often influenced more by diagnostic practices than true epidemiologic differences.
• In England, there were 35,845 hospital admissions for PE between 2022–2023, and 7388 deaths from PE reported between 2019–2021.
• In a study spanning six EU countries, 317,000 deaths were attributed to VTE in 2004. Of these, 34% were sudden fatal PEs, 59% were from PE following undiagnosed VTE, and only 7% were from diagnosed and treated PE.

Population Subgroups

Age

• PE incidence increases significantly with age, with adults over 65 showing markedly higher rates. In the US, hospitalisation rates in this group increased from 129 to 302 per 100,000 person-years between 1999 and 2010.
• Elderly patients are more likely to present atypically and be underdiagnosed. Diagnostic hesitancy due to bleeding risk often leads to undertreatment despite a higher risk of fatal outcomes.

Sex

• Data are inconsistent regarding sex differences. Some studies report 20–30% higher mortality in men, while others show higher incidence in younger women (especially <55 years).
• Overall, men have a greater incidence in older age groups, while women are more affected during reproductive years, partly due to oestrogen-related risk factors.

Race and Ethnicity

• Black populations have significantly higher incidence and 50% higher mortality from PE compared to white populations.
• Conversely, Asian, Pacific Islander, and Native American populations demonstrate lower rates of VTE overall.

Pregnancy

• Pregnancy and the postpartum period are associated with a markedly increased risk of PE.
• A population-based study found a relative risk of 4.29, with an absolute incidence of 199.7 per 100,000 woman-years.
• The postpartum period is particularly high risk, with a five-fold higher rate compared to pregnancy (511.2 vs 95.8 per 100,000 women).
• DVT is about three times more common than PE during pregnancy, but PE predominates postpartum.
• A national review found increasing PE rates correlating with the rise in caesarean sections.

Children

• PE and DVT are rare in children, with an estimated incidence of 0.05–3.7% in autopsy studies.
• In a study of paediatric reports from 1975–1993, 308 children were identified with DVT/PE; more recent estimates suggest 78 per 100,000 hospitalised adolescents may be affected.
• Among paediatric cases, PE contributes to 30% of deaths in affected individuals. However, some studies report lower fatality rates (<5%).
• Central venous catheters and inherited thrombophilias are leading risk factors in this group.

Sedentary Behaviour

• Prolonged sitting is a significant behavioural risk. A prospective cohort of female nurses found that sitting >40 hours per week more than doubled the risk of idiopathic PE compared with those who sat <10 hours.

Postoperative Risk

• PE is responsible for up to 15% of postoperative deaths, especially following major orthopaedic and pelvic surgery, including hip and spinal procedures, and leg amputations.

Dyspnoea

• This is the most common presenting symptom, occurring in approximately 50% of patients.
• It may be acute and severe in central PE or mild and transient in peripheral PE.
• In patients with pre-existing heart failure or chronic lung disease, worsening dyspnoea may be the sole manifestation.
• Tachypnoea is frequently observed and supports the suspicion of PE.

Chest pain

• Typically pleuritic and unilateral, reported in about 39% of cases.
• Often caused by pleural irritation from peripheral emboli leading to pulmonary infarction.
• Central PE may present with angina-like pain due to right ventricular ischaemia, which should be differentiated from acute coronary syndromes or aortic dissection.

Cough

• Occurs in roughly 23% of patients.
• May be dry or productive and sometimes associated with crackles on auscultation.

Haemoptysis

• Seen in approximately 8% of patients, usually indicating pulmonary infarction.
• Must be distinguished from bleeding originating in the upper airways, gastrointestinal tract, or gingiva.
• A detailed history is essential to identify the true source of bleeding.

Fever

• Present in about 10% of cases.
• Low-grade fever may occur in PE, but high fever (>39°C) raises the likelihood of concurrent pneumonia.

Syncope or pre-syncope

• Occurs in around 6% of patients.
• Often suggests a large, centrally located embolus causing right ventricular dysfunction.
• Associated with increased risk of haemodynamic compromise.

Haemodynamic instability

• Found in roughly 5% of presentations.
• Defined by hypotension (systolic BP <90 mmHg or a ≥40 mmHg drop from baseline), need for vasopressors, or signs of obstructive shock.
• Tachycardia, elevated jugular venous pressure, and signs of acute right ventricular dysfunction may be present.

Risk Factors to Identify from the History

Strong Risk Factors

• Active malignancy (particularly brain, pancreas, lung, colon, prostate, or multiple myeloma).
• Recent surgery or hospitalisation within the last 3 months (especially orthopaedic or pelvic procedures).
• Prior history of DVT or PE.
• Pregnancy and postpartum period (especially within the first 6 weeks).
• Immobilisation for >3–5 days or long-haul travel.
• Major trauma to the pelvis or lower limbs.
• Use of combined oral contraceptives or hormone replacement therapy.
• Known thrombophilia (e.g., Factor V Leiden, prothrombin gene mutation, protein C or S deficiency, antithrombin deficiency, antiphospholipid syndrome).

Moderate or Weak Risk Factors

• Obesity (BMI ≥29 kg/m²).
• Increasing age.
• Varicose veins.
• Smoking.
• Chronic heart failure, COPD, nephrotic syndrome, Behçet’s disease.
• Chronic dialysis, myeloproliferative disorders, paroxysmal nocturnal haemoglobinuria.
• Recent blood transfusions.
• Central venous catheters or implanted pacemakers.
• Family history of VTE in a first-degree relative.

Clinical Scoring Systems Based on History

Pulmonary Embolism Rule-Out Criteria (PERC Rule)

• Used in patients with low clinical suspicion to avoid unnecessary testing. PE can be ruled out if all eight criteria below are met:
  • Age <50 years
  • Heart rate <100 bpm
  • Oxygen saturation ≥95% on room air
  • No unilateral leg swelling
  • No haemoptysis
  • No recent surgery or trauma within the last 4 weeks (requiring general anaesthesia)
  • No history of DVT or PE
  • No hormone use (e.g., oral contraceptives or HRT)
• If any criterion is not met, D-dimer testing or imaging should be pursued.

Wells Score (or Geneva Score)

• Used for risk stratification in haemodynamically stable, non-pregnant adults.
• Categorises patients as:
  • PE likely (score >4): Initiate anticoagulation and proceed to imaging.
  • PE unlikely (score ≤4): Perform D-dimer testing. If positive, proceed to imaging.

Wells Score Criteria

• Clinical signs of DVT: 3
• Alternative diagnosis less likely than PE: 3
• Previous DVT or PE: 1.5
• Heart rate >100 bpm: 1.5
• Surgery (last 4 weeks) or immobilisation >3 days: 1.5
• Haemoptysis: 1
• Active malignancy: 1

Pregnancy-Specific Considerations

• Do not apply Wells or Geneva scores during pregnancy.
  
  
• Use YEARS criteria with D-dimer to evaluate suspected PE:
  • Clinical signs of DVT
  • Haemoptysis
  • PE as the most likely diagnosis
• Imaging is indicated if:
  • D-dimer ≥1000 ng/mL with 0 YEARS items
  • D-dimer ≥500 ng/mL with ≥1 YEARS item
• Always involve senior clinicians in decision-making for pregnant patients.

Important Notes

• Approximately 30% of PE cases are unprovoked with no identifiable risk factor.
• Symptoms can be subtle, particularly in elderly patients or those with chronic cardiorespiratory conditions.
• Up to 40% of individuals who die from PE had preceding symptoms that were misdiagnosed or not thoroughly investigated.
• PE may be discovered incidentally on imaging performed for unrelated reasons, emphasising the importance of evaluating risk factors in all relevant clinical scenarios.

Tachypnoea

• Present in over 90% of cases, making it the most consistent physical sign.
• Defined as a respiratory rate >20 breaths per minute.
• May reflect either hypoxaemia or increased dead space ventilation.

Tachycardia

• Occurs in approximately 44% of patients with PE.
• Heart rate >100 bpm is an early compensatory response to impaired cardiac output or hypoxaemia.
• Isolated tachycardia may be the only abnormal finding in some cases.

Hypoxaemia

• Oxygen saturation is <94% in many patients, though up to 40% can have normal SpO₂.
• Desaturation may only become apparent on exertion in patients with smaller emboli.
• Cyanosis, while uncommon, suggests massive PE and significant V/Q mismatch.

Accentuated Pulmonary Component of the Second Heart Sound (Loud P2)

• Seen in 53% of patients in some studies.
• Indicates elevated pulmonary artery pressures secondary to acute obstruction.

Signs of Deep Vein Thrombosis (DVT)

• Present in approximately 24% of PE cases.
• Includes unilateral leg swelling, tenderness, increased warmth, erythema, or a palpable cord.
• Examine the lower limbs for venous distension and skin changes.

Calf Swelling and Tenderness

• Unilateral findings are more specific.
• May be associated with pedal oedema or erythema.

Pleural Rub

• Suggests a peripheral embolus causing pulmonary infarction.
• May be audible during inspiration and accompanied by localised tenderness or reduced chest expansion.

Rales (Crackles)

• Detected in about 58% of patients.
• More likely in infarcted regions or areas of parenchymal inflammation.

Fever

• Found in 10–43% of patients but usually low-grade (<39°C).
• High fever is more suggestive of pneumonia or other infection.

Jugular Venous Distension (JVD)

• Indicates right ventricular dysfunction and elevated right atrial pressure.
• Particularly notable in massive PE causing obstructive shock.

Parasternal Heave and Right Ventricular Lift

• Signs of right ventricular strain.
• Associated with pulmonary hypertension and increased RV afterload.

Gallop Rhythm (S3 or S4)

• Suggests ventricular failure, most commonly right-sided in the context of PE.
• Heard in approximately 34% of patients.

Diaphoresis

• Seen in over one-third of cases.
• Reflects sympathetic activation due to haemodynamic compromise.

Signs of Pulmonary Hypertension

• Includes loud P2, right-sided S3, systolic murmur at the left sternal edge (tricuspid regurgitation), hepatomegaly, ascites, and peripheral oedema.
• These findings often appear with multiple or chronic emboli.

Syncope or Pre-syncope

• Can occur in high-risk PE.
• May be associated with low cardiac output and right ventricular failure.

Delirium or Altered Mental State (especially in elderly)

• May occur in the absence of other symptoms.
• Hypoperfusion or hypoxia should be suspected.

Unusual or Atypical Signs

• Seizures, flank pain, abdominal pain, and decreased consciousness have been reported.
• May be misleading unless correlated with risk factors and other signs.

Massive PE (High-Risk Presentation)

• Signs include shock, hypotension, oliguria, cold extremities, altered mentation, and weak pulses.
• PE accounts for up to 8% of sudden cardiac arrests.
• New right bundle branch block or wide complex tachycardia may indicate RV strain and impending collapse.

Children

• Signs may be subtler due to better haemodynamic reserve.
• Common findings include cough and tachypnoea.
• Haemoptysis and cyanosis are less frequent but suggest severe disease.
• Signs of pulmonary hypertension (e.g., loud P2, JVD) may indicate more extensive disease.
• Pleural rub, if present, supports a diagnosis of peripheral embolisation.

• Localised pleuritic chest pain, haemoptysis, and breathlessness.
• Dullness to percussion, reduced breath sounds, and friction rub over the involved hemithorax.
• These signs are often accompanied by decreased expansion and localised tenderness.

Multiple Emboli or Chronic Thromboembolic Disease

• Signs of cor pulmonale such as peripheral oedema, elevated JVP, hepatomegaly, and right-sided murmurs.
• Typically seen in patients with recurrent PE or undiagnosed chronic thromboembolic pulmonary hypertension.

Computed Tomographic Pulmonary Angiography (CTPA)

• First-line imaging for diagnosing PE in haemodynamically stable patients.
• Directly visualises intraluminal filling defects in the pulmonary arteries.
• Indicated in patients with a 'PE likely' Wells/Geneva score or a positive D-dimer.
• Can also assess right ventricular (RV) dysfunction using RV:LV diameter ratio >0.9.
• Avoid in patients with renal dysfunction or contrast allergy; consider alternatives in younger patients due to radiation risk.

Echocardiography

• Used in haemodynamically unstable patients who cannot be moved for CTPA.
• Detects RV dysfunction (e.g., dilatation, hypokinesis, McConnell’s sign, septal flattening).
• Can identify alternate causes of shock (e.g., tamponade, aortic dissection).
• Positive findings support diagnosis and justify emergency reperfusion.
• Not reliable for exclusion—negative echocardiogram does not rule out PE.

D-dimer Testing

• High sensitivity (>95%) but low specificity; most useful in low pre-test probability cases.
• In non-pregnant patients aged ≥50 years, an age-adjusted threshold improves utility.
• In pregnancy, use alongside YEARS criteria to stratify risk.
• A normal result in low-risk patients can safely exclude PE (3-month event rate <1%).
• Elevated results require further imaging (CTPA or leg ultrasound if DVT suspected).

Electrocardiography (ECG)

• Non-diagnostic but may support PE suspicion or exclude other causes (e.g., MI).
• Common findings: sinus tachycardia, S1Q3T3 pattern, new RBBB, T wave inversion in V1–V4.
• Right heart strain signs may be present in massive PE.

Chest X-ray (CXR)

• Usually normal; used to exclude alternative diagnoses.
• Potential PE indicators: pleural effusion, atelectasis, hemidiaphragm elevation, Hampton’s hump, or Westermark’s sign.

Full Blood Count (FBC)

• May show anaemia, thrombocytopenia (from heparin-induced thrombocytopenia), or thrombocytosis.
• Thrombocythaemia/polycythaemia may indicate an underlying prothrombotic state.

Renal and Liver Function Tests

• Required before initiating anticoagulants like LMWH or DOACs.
• Guide safe use of contrast agents for imaging.
• Abnormal liver function may influence anticoagulant choice.

Coagulation Studies

• INR, PT, and aPTT are essential before starting anticoagulation.
• Baseline values assist in identifying coagulopathy and guiding therapy.

Arterial Blood Gas (ABG)

• Consider in patients with hypoxaemia on pulse oximetry.
• Classic findings: hypoxaemia, hypocapnia, and respiratory alkalosis.
• Normal ABG does not exclude PE; limited diagnostic value in isolation.

Lower Limb Compression Ultrasound

• Perform if concurrent DVT is suspected.
• A positive scan may justify treatment for PE without further imaging.
• Useful alternative when CTPA is contraindicated.

Cardiac Biomarkers (Troponin, BNP, NT-proBNP)

• Not diagnostic but help in prognostication and risk stratification.
• Elevated troponin indicates RV strain; associated with increased mortality.
• BNP and NT-proBNP elevations correlate with adverse outcomes and may identify patients requiring hospitalisation.

Ventilation–Perfusion (V/Q) Scan

• Preferred in patients with contraindications to contrast or renal dysfunction.
• High-probability scan: ventilation–perfusion mismatch (normal ventilation with perfusion defects).
• Less accurate in patients with lung disease; limited by intermediate and non-diagnostic results.
• Useful in pregnancy if chest X-ray is normal.

Further Investigations for Unprovoked PE

• Basic cancer screening (history, exam, FBC, renal/hepatic function, PT/aPTT) only if symptoms suggest underlying malignancy.
• Avoid extensive screening unless clinically indicated.
• Consider antiphospholipid antibody and hereditary thrombophilia testing if discontinuation of anticoagulation is planned.
• Thrombophilia tests may be affected by ongoing anticoagulation—specialist input may be needed.

Emerging or Rarely Used Modalities

Magnetic Resonance Angiography (MRA)

• Non-invasive, no radiation, avoids iodinated contrast—beneficial for patients with renal impairment.
• Limited by lower sensitivity for subsegmental emboli and availability.
• Not yet widely used in clinical practice.

Pulmonary Angiography

• Former gold standard; now rarely used.
• Invasive but definitive—reserved for inconclusive CTPA and V/Q scans when PE suspicion remains high.
• Positive findings have near 100% specificity; negative angiograms highly predictive for excluding PE.

Ischaemia-Modified Albumin (IMA)

• May provide diagnostic utility in combination with clinical scores.
• Higher sensitivity than D-dimer in some studies but not yet standard practice.

Acute Coronary Syndromes (ACS)

• Chest pain in ACS is typically central, crushing, and radiating to the jaw, arm, or neck.
• ECG may reveal ST-segment depression (NSTEMI) or elevation (STEMI); troponin levels are elevated.
• Regional wall motion abnormalities can be seen on echocardiography.
• PE can also cause elevated troponin and ECG changes, thus clinical context is critical.

Pericarditis

• Pleuritic chest pain that improves on sitting forward and worsens when supine.
• ECG shows widespread ST elevation and PR depression; may see electrical alternans with effusion.
• Echocardiography can identify pericardial effusion; PE and pericarditis may coexist or be confused.

Cardiac Tamponade

• Presents with hypotension, muffled heart sounds, and raised JVP (Beck’s triad).
• Dyspnoea and chest pain may mimic PE.
• Echocardiography confirms diagnosis by showing pericardial effusion and signs of tamponade physiology.

Congestive Heart Failure (CHF)

• Dyspnoea, orthopnoea, and peripheral oedema with a more gradual onset than PE.
• Bilateral basal crackles and elevated BNP levels are common.
• Chest radiography shows pulmonary congestion; echocardiography reveals reduced LV function.
• BNP can also be mildly elevated in PE due to RV strain, but rarely exceeds 1000 pg/mL.

Pneumonia

• Symptoms include productive cough, high fever (>39°C), and pleuritic chest pain.
• Elevated white cell count and focal consolidation on chest X-ray.
• Differentiation from PE is difficult, especially with infarct-related infiltrates.

Acute Bronchitis

• Subacute onset of cough, often productive, with wheezing and rhonchi on examination.
• Normal chest X-ray and D-dimer.
• Unlike PE, bronchitis rarely causes hypoxia or haemodynamic compromise.

COPD Exacerbation

• Presents with dyspnoea, cough, and wheezing in patients with known smoking history.
• Chest radiograph shows hyperinflation; spirometry confirms airflow limitation.
• PE can coexist, especially if exacerbation is unexplained or disproportionate to findings.

Asthma Exacerbation

• History of atopy, episodic wheeze, and reversibility on spirometry.
• Diffuse wheezes and reduced breath sounds on auscultation.
• Normal chest radiograph; D-dimer and CTPA usually not suggestive of PE.

Pneumothorax

• Sudden-onset pleuritic chest pain and dyspnoea.
• Decreased breath sounds and hyper-resonance unilaterally; tracheal deviation in tension pneumothorax.
• Chest X-ray confirms diagnosis with visible loss of lung markings.

Pulmonary Hypertension (Chronic Thromboembolic Disease)

• Progressive dyspnoea with signs of RV dysfunction.
• May present with pulmonary flow murmurs, right axis deviation on ECG, and elevated BNP.
• Ventilation-perfusion (V/Q) scan reveals unmatched perfusion defects.
• Pulmonary angiography confirms chronic thromboembolic lesions.

Fat Embolism Syndrome

• Often follows long bone fractures or orthopaedic surgery.
• Presents with respiratory distress, petechial rash, and neurological symptoms.
• Diagnosis is clinical; imaging may show diffuse infiltrates.

Aortic Dissection

• Sudden-onset tearing chest or back pain; may mimic PE when pain is anterior.
• Differential blood pressures in limbs, widened mediastinum on CXR.
• CT angiography distinguishes from PE by visualising dissection flap.

Costochondritis

• Localised anterior chest wall pain worsened by palpation or movement.
• No systemic signs or radiological findings.
• PE may coexist but is unlikely in isolated reproducible chest wall tenderness.

Idiopathic Pulmonary Arterial Hypertension (IPAH)

• Progressive exertional dyspnoea and signs of right heart failure.
• Exclusion of secondary causes including PE is essential.
• V/Q scanning is often normal, unlike in chronic thromboembolic pulmonary hypertension.

Syncope (Vasovagal or Cardiogenic)

• Sudden loss of consciousness may be due to PE, especially with associated RV strain.
• Vasovagal syncope typically occurs in response to emotional or orthostatic stress.
• Cardiogenic causes include arrhythmias, structural heart disease, or massive PE.

Anxiety/Panic Attacks

• Palpitations, chest discomfort, dyspnoea with normal physical exam and investigations.
• Diagnosed clinically and confirmed with psychiatric evaluation.
• D-dimer and imaging rule out PE in low-risk patients.

Haemodynamically Unstable Patients (High-Risk PE)

Definition

• Systolic BP <90 mmHg or a drop of ≥40 mmHg from baseline for >15 minutes
• Clinical signs of shock: altered mental status, cold extremities, oliguria, elevated lactate
• Cardiac arrest or peri-arrest state

Immediate Actions

• ABCDE assessment with early senior involvement and critical care escalation
• Do not delay thrombolysis in peri-arrest if PE is strongly suspected

Supportive Measures

• Oxygen therapy: High-flow oxygen to maintain saturations of 94–98%; 88–92% in patients at risk of hypercapnic respiratory failure
• Mechanical ventilation only if necessary, as positive pressure ventilation may reduce preload and worsen right ventricular (RV) output
• Intravenous fluids: Administer a cautious bolus (≤500 mL over 15–30 minutes) only if JVP is not elevated. Overhydration can worsen RV failure
• Vasoactive agents: Initiate norepinephrine or dobutamine in persistent hypotension despite fluids

Reperfusion Therapy

• Systemic thrombolysis is the first-line intervention
  • Preferred agent: Alteplase 100 mg IV over 2 hours
  • Start UFH prior to thrombolysis; hold during streptokinase or urokinase infusion
  • Consider bleeding risk; in most cases, contraindications to thrombolysis are relative in unstable PE
• Rescue therapy options if thrombolysis fails or is contraindicated:
  • Surgical pulmonary embolectomy
  • Catheter-directed thrombolysis or mechanical thrombectomy
  • Selection depends on institutional availability and patient profile

Post-reperfusion anticoagulation

• Continue UFH for several hours post-thrombolysis, then transition to oral agents (e.g., apixaban/rivaroxaban) or LMWH
• Monitor closely for bleeding, haemodynamic instability, and recurrent PE

Haemodynamically Stable Patients with Intermediate-Risk PE

Definition

• Normal BP but with features indicating right heart strain
• Intermediate-high risk: RV dysfunction and elevated cardiac biomarkers
• Intermediate-low risk: Only one of RV dysfunction or biomarker elevation

Initial Management

• Admit to monitored setting for close observation (e.g., step-down or high-dependency unit)
• Initiate anticoagulation immediately (unless contraindicated):
  • Apixaban or rivaroxaban (no LMWH lead-in required)
  • LMWH or UFH if DOACs not suitable
• Do not administer thrombolysis routinely
  • Monitor closely for clinical deterioration
  • Administer rescue thrombolysis if haemodynamic instability develops

Monitoring Parameters

• Continuous ECG and oxygen saturation monitoring
• Daily assessment of:
  • Haemodynamic status
  • RV function (e.g., follow-up echo if symptoms worsen)
  • Biomarkers (troponin, BNP/NT-proBNP)

Haemodynamically Stable Patients with Low-Risk P

Definition

• Normal BP
• No RV dysfunction
• Normal cardiac biomarkers
• PESI score I–II or sPESI score 0
• No high-risk comorbidities or social barriers

Initial Management

• Start anticoagulation promptly
  • Apixaban or rivaroxaban preferred for outpatient suitability
  • LMWH is an alternative (e.g., in cancer or renal impairment)
• No need for thrombolysis or intensive monitoring

Outpatient Criteria (must meet all)

• sPESI = 0
• Normoxia (SpO₂ >90% on room air)
• No active bleeding risk
• No severe pain or comorbidity requiring inpatient care
• Adequate home support and ability to follow up

Follow-up Planning

• Confirm diagnosis with CTPA within 24 hours if not done prior to discharge
• Arrange outpatient review within 1 week
• Provide written advice on:
  • Symptoms of recurrence
  • Bleeding signs
  • Emergency contact information

Anticoagulation Duration by Clinical Scenario

Provoked PE (e.g., surgery, trauma)

• Minimum Duration: 3 months
• Extended Treatment: Usually not required unless ongoing risk

Unprovoked PE

• Minimum Duration: 3 months
• Extended Treatment: Consider indefinite anticoagulation based on bleeding risk

Active cancer

• Minimum Duration: 3–6 months
• Extended Treatment: Continue while cancer is active or treatment ongoing

Recurrent PE

• Minimum Duration: Individualised
• Extended Treatment: Consider dose escalation or switch of agent

Pregnancy

• Minimum Duration: Throughout pregnancy + ≥6 weeks postpartum (minimum 3 months)
• Extended Treatment: LMWH preferred

Special Considerations

Pregnancy

• Use weight-adjusted LMWH
• Avoid DOACs and warfarin during pregnancy
• Anticoagulation compatible with breastfeeding: warfarin, LMWH, UFH

Renal Failure (CrCl <30 mL/min)

• Prefer UFH or adjusted-dose LMWH
• DOACs may be used with caution depending on drug and renal function

Active Cancer

• First-line: DOAC (e.g., apixaban) based on tumour location and bleeding risk
• LMWH remains acceptable if DOAC not suitable

Thrombophilia or Antiphospholipid Syndrome

• Avoid DOACs in triple-positive antiphospholipid syndrome
• Use warfarin with INR monitoring

Impact of Haemodynamic Instability and Right Ventricular Dysfunction

• Haemodynamic instability, defined by systolic blood pressure (SBP) <90 mmHg or the presence of shock, is strongly associated with increased mortality in acute PE.
• Right ventricular (RV) dysfunction on imaging or biomarker testing is a significant adverse prognostic marker. It reflects increased afterload and strain, which may lead to RV failure—a leading cause of death in high-risk PE.
• Meta-analysis evidence indicates that haemodynamically stable patients with RV dysfunction have a more than twofold increased risk of short-term mortality compared with those without RV dysfunction (odds ratio 2.29, 95% CI 1.61–3.26).
• In one analysis, in-hospital or 30-day mortality occurred in 13.7% of patients with RV dysfunction versus 6.5% of those without.

Effect of Coexisting Conditions and Complications

• Patients presenting with PE and coexisting deep vein thrombosis (DVT) have a higher mortality risk compared to those with isolated PE.
• While earlier data suggested high mortality with pulmonary infarction, recent findings show a 97% survival-to-discharge rate in such cases, reflecting improved diagnostics and supportive care.
• Pulmonary infarction, although painful and occasionally associated with haemoptysis, does not necessarily predict adverse outcome in the absence of haemodynamic instability.

Role of Hypotension

• Hypotension is a consistent marker of poor prognosis:
  • In the EMPEROR registry, inpatients with PE and hypotension had significantly higher all-cause inpatient mortality (13.8% vs 3.0%) and 30-day mortality (14.0% vs 1.8%) compared with normotensive patients.
  • The RIETE registry showed a 90-day mortality of 9.3% in patients with symptomatic PE and hypotension, compared to 3.0% in those with non-massive PE.

Prognostic Stratification Tools

Pulmonary Embolism Severity Index (PESI)

• A validated tool that estimates 30-day mortality in patients with confirmed PE.
• Integrates multiple clinical variables, including age, comorbidities, and physiological derangements.

PESI Variables and Scoring

• Age (in years) = score
• Male sex = +10
• History of cancer = +30
• Chronic heart failure = +10
• Chronic pulmonary disease = +10
• Pulse ≥110 bpm = +20
• SBP <100 mmHg = +30
• Respiratory rate >30 = +20
• Temperature <36°C = +20
• Altered mental status = +60
• Arterial oxygen saturation <90% = +20

PESI Risk Classes

• Class I (≤65 points): 1.1–1.6% mortality (very low)
• Class II (66–85 points): 1.7–3.5% (low)
• Class III (86–105 points): 3.2–7.1% (intermediate)
• Class IV (106–125 points): 4.0–11.4% (high)
• Class V (>125 points): 10–24.5% (very high)

Simplified PESI (sPESI)

• Easier to apply clinically; dichotomises risk into low and high categories.
• Variables (1 point each):
  • Age >80 years
  • History of cancer
  • Chronic cardiopulmonary disease
  • Heart rate ≥110 bpm
  • SBP <100 mmHg
  • O₂ saturation <90%

sPESI Interpretation

• 0 points: 30-day mortality ~1%
• ≥1 point: 30-day mortality ~10.9%
• sPESI is particularly helpful in identifying patients suitable for outpatient management or early discharge.

Clinical Implications of Prognostic Assessment

• Low-risk patients (PESI class I–II or sPESI 0) may be eligible for outpatient therapy with direct oral anticoagulants.
• Intermediate-risk patients (PESI III–IV or sPESI ≥1 with RV dysfunction or raised biomarkers) require close inpatient monitoring and consideration of escalation if deterioration occurs.
• High-risk patients (haemodynamically unstable, PESI V or RV failure with shock) should receive urgent reperfusion therapy.

Recurrent Thromboembolism

• Timeframe: Early (within 1–2 weeks), but may also occur later
• Likelihood: Medium
• Details: Inadequate or interrupted anticoagulation is the leading cause of recurrent venous thromboembolism (VTE). High-risk periods include the first month following the initial event. Recurrence may be heralded by sudden worsening dyspnoea or new chest pain.
• Management: Ensure timely initiation and maintenance of therapeutic anticoagulation. Evaluate adherence and underlying prothrombotic conditions.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

• Timeframe: Long-term (typically diagnosed 3–24 months after PE)
• Likelihood: Low (1.5%–3.8%)
• Details: Persistent obstruction of pulmonary arteries leads to progressive pulmonary hypertension and right heart strain. Symptoms include exertional dyspnoea, fatigue, and reduced exercise tolerance. CTEPH can develop despite anticoagulation and in cases without massive PE.
• Diagnostic Work-up:
  • Initial suspicion: persistent dyspnoea >3 months post-PE.
  • Screening: ventilation-perfusion (V/Q) scan — identifies mismatched perfusion defects.
  • Confirmation: right heart catheterisation and pulmonary angiography.
• Treatment: Lifelong anticoagulation, referral for pulmonary endarterectomy (definitive treatment in selected patients), and consideration of medical therapy (e.g., riociguat) in non-surgical candidates.

Right Ventricular Failure

• Timeframe: Short-term (acute decompensation)
• Likelihood: Medium to high in massive PE
• Details: Acute pressure overload from obstructed pulmonary circulation can lead to RV dilation, reduced LV filling, and systemic hypotension. It is the primary mechanism of death in high-risk PE.
• Management: Immediate reperfusion therapy (systemic thrombolysis, surgical or catheter-directed therapy), cautious fluid management, and inotropic/vasopressor support.

Cardiogenic Shock and Cardiac Arrest

• Timeframe: Immediate
• Likelihood: Low (but high mortality if it occurs)
• Details: Seen in <5% of PE cases, typically with massive PE. Resulting RV failure leads to collapse of cardiac output.
• Mortality: 65%–90% in cardiac arrest due to PE.
• Management: Aggressive resuscitation, emergency thrombolysis, or extracorporeal membrane oxygenation (ECMO) where available.

Pulmonary Infarction

• Timeframe: Acute
• Likelihood: Low
• Details: Results from obstruction of smaller distal pulmonary arteries without sufficient bronchial circulation collateral flow. Presents with pleuritic chest pain, haemoptysis, and focal consolidation on imaging.
• Management: Supportive care, analgesia, and anticoagulation.

Bleeding Complications During Anticoagulation

• Timeframe: During treatment
• Likelihood: Medium (varies with risk profile)
• Major risk factors:
  • Age >65 years, especially >75
  • History of bleeding or stroke
  • Renal or hepatic impairment
  • Cancer (especially metastatic)
  • Anaemia, thrombocytopenia
  • Concomitant antiplatelets, NSAIDs, or alcohol misuse
• Sources of bleeding: Gastrointestinal, intracranial, genitourinary, or unrecognised vascular malformations.
• Management: Risk-benefit review prior to anticoagulation; consider DOACs with lower bleeding profiles or use LMWH where appropriate. Employ bleeding risk assessment tools (e.g., HAS-BLED) and monitor regularly.

Heparin-Induced Thrombocytopenia (HIT)

• Timeframe: 5–10 days after heparin initiation
• Likelihood: Low (0.1%–1%)
• Mechanism: IgG-mediated immune reaction to heparin–platelet factor 4 complexes, causing platelet activation and paradoxical thrombosis.
• Risk factors: Surgical/orthopaedic patients, unfractionated heparin use, female sex, prolonged heparin exposure.
• Management:
  • Discontinue all forms of heparin.
  • Initiate non-heparin anticoagulant (e.g., fondaparinux, argatroban).
  • Confirm with HIT antibody testing.
  • Avoid re-exposure to heparin.

Recurrent VTE Despite Anticoagulation

• Timeframe: Variable
• Likelihood: Medium
• Details: In rare cases, PE recurs despite therapeutic anticoagulation.
• Possible causes: Inadequate dosing, poor adherence, drug interactions, underlying malignancy or thrombophilia.
• Management:
  • Switch anticoagulant class (e.g., from DOAC to LMWH).
  • Dose escalation under specialist guidance.
  • Evaluate for antiphospholipid syndrome or occult malignancy.
  • Consider inferior vena cava (IVC) filter if anticoagulation is contraindicated.

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