see also: EMedicine.com - PE

• Ix of suspected pulmonary embolism (PE)
• Mx of PE (Pulmonary Embolism)
• Mx of suspected or actual DVT (Deep Vein Thrombosis)
• historical perspectives of PE
• anticoagulants
• pulmonary vein thrombosis (PVT)

• thrombotic pulmonary embolism occurs from dislodgment of a thrombus in a systemic vein - usually a deep vein of the legs (DVT) - which then passes through the RA an RV into the pulmonary artery where it may wedge to become an immediately life threatening “saddle embolus”, or may pass into more distal pulmonary arteries with usually lesser immediate clinical effects depending upon clot burden.
• in 2026, the AHA introduced a new paradigm for categorising PE severity and Mx based on the A-E categories to replace older classifications such as low risk / intermediate risk / high risk or massive / submassive. They also decided that LMW heparin is now preferred over unfractionated heparin and that a DOAC is preferred over warfarin. Low risk categories of A and B could be recommended for early discharge and outpatient Mx. Catheter directed thrombolysis or thrombectomy is now becoming the preferred Mx of those in category D or E having been given a class 2A recommendation. Systemic thrombolysis (potentially with lower dose) should be considered for those in categories D and E if catheter directed modalities are not available or preferred, or patient is E2. They also suggest reviewing patients every 3 months and if symptomatic, re-imaging with referral of those with evidence of residual vascular obstruction for cardiopulmonary exercise testing to consider advanced interventions.¹⁾

• deep venous thrombosis (DVT) & PE are much more common than is usually realised
• without anticoagulant prophylaxis, acute DVT's are found in (50% of these will have PE):
  • 10-13% of all general medical pts admitted for bedrest > 1wk
  • 29-33% of medical ICU pts
  • 20-26% of pulm. disease pts kept in bed >= 3 days
  • 27-33% of CCU pts post-AMI
  • 48% of asymptomatic pts post-CAG surgery
• prophylactic heparin given to medical pts admitted via ED reduced overall mortality by 31%
• having an autopsy tends to double the likelihood that PE will be listed on death certificate
• PE was found in 18.5% of consecutive autopsies & were responsible for 11% of all deaths
• PE is 2nd only to AMI as a cause of sudden unexpected natural death at any age & the Dx is especially likely to be missed in older pts:
  • in pts dying of massive PE, correct Dx made in 30% overall, but only 10% in those aged > 70yrs
• PE is the single most common unsuspected cause of death in pts who die while on ventilator
• Bedell found a major missed diagnosis in 14% of pts who die in hospital & had autopsy after CPR:
  • 90% of these major missed diagnoses were PE's or bowel ischaemia
• at autopsy of pts clinically diagnosed with primary pulm. HT, 57% will have chronic pulm. thromboembolism rather than primary pulm. HT (the Mx is different for each of these diseases!!)
• The bad news about thromboembolism:
  • most DVTs are asymptomatic
  • most DVTs produce PEs although many are asymptomatic
  • many DVTs are not detectable by current imaging techniques
  • some PEs will cause sudden death - PE causes ~3% of out of hospital cardiac arrests (OHCA)
  • high thrombus load PEs may result in long term pulmonary hypertension issues
  • non-detectable DVTs & PEs may progress, with recurrences that can cause sudden death and chronic morbidity
• Some good news
  • “asymptomatic” PEs found incidentally and those with minimal symptoms may not need anticoagulation according to AHA 2026 consensus

• equates with 2026 AHA ACC category Emergency E2 refractory / arrest if > 30min refractory shock or arrest

• systolic BP < 90mmHg or less than 40mmHg below usual BP for more than 15 minutes requiring high dose vasopressor support, or,
• persistent bradycardia HR < 40 with clinical features of shock, or,
• patient in extremis (diaphoretic, mottled, confused, sensation of dying)
• may equate with 2026 AHA ACC category Emergency E1 shock if persistent hypotension or E2 refractory / arrest if refractory shock > 30min

• systolic BP < 90mmHg or less than 40mmHg below usual BP for more than 15 minutes but not requiring high dose vasopressor support, or,
• persistent bradycardia HR < 40
• may equate with 2026 AHA ACC category Emergency E1 shock if persistent hypotension or incipient failure either: D1 transient BP drop or D2 normotensive shock if raised lactate > 2.0, AKI or mental state alteration
• any patient with 2026 AHA ACC category D or E should be considered for advanced Rx such as systemic thrombolysis, catheter-directed thrombolysis or thrombectomy

• no features of massive but either:
  • raised troponin,
  • RV dysfunction on echo,
  • large clot seen in RV,
  • raised lactate,
  • diaphoresis, mottled, severe tachypnoea, or,
  • shock index (HR/SBP) > 1, or,
  • Neutrophil to lymphocyte ratio >9.2 in patients with no other cause for a raised neutrophil count (suggests high mortality risk of around ~26%)
• may equate with 2026 AHA ACC category Danger incipient failure either: D1 transient BP drop or D2 normotensive shock if raised lactate > 2.0, AKI or mental state alteration
  • if haemodynamically stable with PESI > 65, but RV dysfunction or raised troponin then may equate with 2026 AHA ACC category Complicated elevated risk either: C2 if one marker present or C3 if both markers present and this category should be admitted and signal need for a multidisciplinary response

• no features of higher severity as above, but:
  • large clot burden on CT scan, and,
  • definite RV dilatation, and,
  • euvolaemic (no other cause for any haemodynamic instability such as dehydration or blood loss)
• may equate with 2026 AHA ACC category Complicated elevated risk C1 if no RV dysfunction and normal troponin

• symptomatic patients without the above and with PESI score ⇐ 65 or sPESI = 8
• may equate with 2026 AHA ACC category Benign either: B1 if subsegmental or B2 if proximal but low clinical score - and these patients may be able to avoid anticoagulation apparently and potentially managed as outpatient

• incidentally found PE whilst looking for something else and not causing any symptoms
• equates with 2026 AHA ACC category Asymptomatic A1 these patients may be able to avoid anticoagulation apparently and potentially managed as outpatient

• not really useful in an ED setting as we need more acute mortality risk scoring, and those with high-risk submassive PE may have a low PESI score

• interpretation:
  • ≤ 65 = class I (very low risk)
  • 66-85 = class II (low risk)
  • 86-105 = class III (intermediate risk)
  • 106-125 = class IV (high risk)
  • ≥ 126 = class V (very high risk)

• 10% of pts with acute PE will die in 1st 60min
  • presence of shock increases mortality 3-7x, with most deaths occurring within 1hr presentation²⁾
• mortality rates in the 1st 3 days following diagnosis depends upon severity of presentation³⁾:
  • cardiac arrest on arrival = ~95%
  • requiring mechanical ventilation or CPR = ~80%
  • syncope = ~40%
  • haemodynamically stable patients who have echocardiographic evidence of right ventricular dysfunction = 15% (and a further 8% mortality within 1 yr if survive to discharge from hospital)⁴⁾
  • all “stable” patients who had CT-PA or V/Q = 1-2%
• massive PE
  • 90 day mortality: 58% (International Cooperative Pulmonary Embolism Registry (ICOPER) )
• sub-massive PE with abnormal RV function and raised troponin levels:
  • hemodynamically stable PE, with an RV/LV transverse ratio on CTPA ≥ 0.9 was associated with increased death or clinical deterioration (HR 3.8, 95% CI 1.3–10.9, p = 0.007) ⁵⁾
  • elevated troponins were associated with increased short-term death (OR 5.24; 95% CI 3.28–8.38) ⁶⁾
  • raised high-sensitive cardiac troponin T (hsTnT) also showed increased death (OR 3.80, 95% CI 2.74–5.27) ⁷⁾
  • in normotensive PE patients, hsTnT levels ≥ 14 pg/mL had a PPV and NPV for adverse 30 day outcomes of 8% and 100%, respectively ⁸⁾
  • ? 5% mortality in 1st 48hrs with early anticoagulation
  • 30 day mortality with anticoagulation: PEITHO study: 1.2% Becattini et al study: 7.7% I-COPER registry: 16% ⁹⁾
  • 90 day mortality of all “sub-massive” cases: 15% (International Cooperative Pulmonary Embolism Registry (ICOPER) )
• of those patients who do not present with massive PE:
  • 1/3rd will be eventually diagnosed & Rx:
    • of these 1 in 12 will die from massive PE or complications of PE
  • 2/3rds will remain undiagnosed (ie. 400,000 cases /yr in USA):
    • of these, 1/3rd will die
• survivors will be at risk of:
  • recurrent PE's
    • risk is dependent upon:
      • persisting underlying cause for thrombosis (eg. cancer, thrombophilia)
      • “unprovoked” PE
      • elevated D-Dimer after cessation of anticoagulant Rx
      • compliance with anticoagulation Rx
  • chronic thromboembolic pulmonary hypertension (CTEPH)
    • 4% of treated patients by 2 yrs after PE
    • risk depends upon:
      • more than one episode of PE (odds ratio, 19.0)
      • younger age (odds ratio, 1.79 per decade)
      • a larger perfusion defect (odds ratio, 2.22 per decile decrement in perfusion)
      • idiopathic pulmonary embolism at presentation (odds ratio, 5.70)¹⁰⁾

• apart from gynae. surgery pts & major trauma pts, lower extremity venous thrombosis virtually always starts in the calf veins, and propagates above the knee in 87% of cases with symptomatic DVT
• in pts with PE, 70% have DVT evident on venograms (?50% on US) although up to 90% of all PEs arise from pelvic or lower DVTs
• risk of embolisation from DVTs:
  • ileofemoral: ~100%
  • popliteal-femoral: 60-80% (half of these PEs will be asymptomatic) - degree of proximity not important
  • calf veins: 33-46%
    • 35% of pts with PE
    • 25% of lethal PEs
    • 33% of “serious” PEs (NB. all PE's are clinically significant as minor ones may just be sentinal events!)
• see Deep venous thrombosis

• amniotic fluid embolism:
  • most commonly occurs near end of 1st stage of labour, but also in abortion or immediate post-partum period
  • Mx:
    • empty the uterus
    • Rx DIC which contributes to the 80% mortality rate
• fat embolism:
  • most commonly occur after fractures of long bones
  • fat globules pass through pulm. circulation to enter systemic circulation where end-organs are affected via obstruction of end-capillaries causing petechiae, CNS symptoms (headache, irritability, convulsions, coma), ARDS, thrombocytopenia
  • Mx:
    • high-dose steroid Rx
    • heparin is C/I as theoretical risk of increasing production of toxic fatty acids in the lungs.
• air embolism:
  • generally iatrogenic, but may be from pressurised underwater breathing apparatus, air-powered drills, vaginal insufflation (in orogenital sex, esp. in pregnancy)
  • often venous (causing circulatory collapse) and arterial (causing CNS impairment)
  • clinical syndrome:
    • loud churning murmur over precordium
    • air bubbles within heart may be seen on echo
    • circulatory collapse may result from as little as 5ml/kg of air forming an air lock in RV or pulm. circulation
  • Mx:
    • left lateral position in an attempt to trap air within RA
• other embolism:
  • bile:
    • post-percutaneous transhepatic drainage for Ca pancreas
  • tumour:
    • ~20% of embolism deaths in pts with solid cancers
  • bone marrow:
    • assoc. with # long bones or sternum/ribs in CPR
  • IV drug preparations
  • broken catheters
  • parasites
  • bullets
  • cardiac vegetations
  • calcium cement:
    • calcium cement may leak into the IVC after percutaneous vertebroplasty (PV) and may then embolise (this appears to complicate the procedure in 7-23% of cases) ¹¹⁾

• blockage of one portion of pulm. vasculature causes increased pulm. vasc. resistance
  • ⇒ increased pulm. arterial pressures (if > 25% pulm. vasculature blocked)
    • ⇒ increased RV pressures
    • ⇒ if > 50% blocked then:
      • signif. pulm. HT results with cor pulmonale
        • in extreme cases, with PABP > 40mmHg, TI results
      • haemodynamic collapse may occur ⇒ death
  • ⇒ V/Q mismatches ⇒ nonperfused lung converted into physiologic dead space
    • ⇒ increased minute ventilation (~1% increase per 1% decrease in perfused alveoli)
      • eg. 15% increase via RR 14to16/min or 150ml increase in tidal volume ⇒ subtle!
  • pain/anxiety ⇒ further hyperventilation
  • after 24hrs, localised alveolar oedema may occur ⇒ rales
  • release of neurohumoral factors may ⇒ pulm. vasoconstriction & bronchoconstriction ⇒ rhonchi
• small recurrent PE's:
  • pulm. arterial endothelium is relatively incapable of lysing thrombus so most emboli remain there permanently!!
    • V/Q & angio. abn. often resolve but this is by organisation & recanalisation
      • decreased pulm. vascular distensibility, thus any attempt to increase cardiac output results in increased pulm. vasc. resistance
        • ⇒ cardiac output can only increase if PABP increases enough to overcome this additional resistance
          • ⇒ pulmonary HT ⇒ chronic cor pulmonale

• clinically apparent factor(s) present in 90% of pts with PEs:
  • past DVT/PE - single strongest risk factor for recurrence (RR 15-30x)
  • immobilisation
  • malignancy
  • stroke
  • recent surgery
  • pregnancy & post partum:
    • recognised thromboembolism occurs in 3-4/1000 births
    • accounts for 20-50% of maternal mortality
    • 75% of clinically recognised PEs occur antepartum, > 50% in 1st 15wks gestation, HOWEVER, it is likely that incidence is equal in each of the trimesters, it just gets harder to diagnose later in pregnancy
    • gradient compression stockings are strongly recommended for all pregnant pts
    • NB. post-partum endometritis:
      • risk of septic pelvic vein thrombophlebitis ⇒ septic pulmonary emboli in 40% if untreated
      • thus consider anticoagulant Rx in pts with significant post-partum endometritis
    • NB. ovarian vein thrombosis:
      • diagnosis is rarely clinically apparent & usually made laparoscopically or at C.S. or on CT
      • thrombus may extend into vena cava in which case a vena caval filter is indicated
• cardiac failure, AMI
• haematological factors (usually not clinically apparent)
• obesity (> 20% more than ideal)
• see also: haemostasis pathophysiology

• PE is known as “the great masquerader”
• pleuritic chest pain
• “pneumonia”
• “asthma”
  • “All that wheezes is not asthma” (Chevallier Jackson). PE may appear as asthma when diffuse wheezing results from the release of vasoactive and bronchoactive mediators. 10-20% of PE patients present with wheezing.
• “pleurisy”
• “angina” (4-30% present & misdiagnosed as angina)
• “AMI” (PE is 10% of deaths in pts Dx with AMI)
  • conversely, AMI is the most common cause of death when clinical Dx of PE is incorrect!
• paradoxical embolism (usually from calf DVTs which tend have smaller emboli):
  • 27% adults have patent foramen ovale
• pulmonary infarction mimicking “bronchogenic carcinoma” or if cavitates, a “lung abscess” on CXR or V/Q
• “psychosomatic hyperventilation” or “anxiety disorder”
• collapse, cardiac arrest with PEA and death - within 2 hrs of onset of massive PE

• dyspnoea (73%)
• pleuritic pain (66%)
• cough (37%)
• leg oedema (28%)
• leg pain (26%)
• haemoptysis (13%)
• palpitations (10%)
• wheeze (9%)

• tachypnoea (70%)
• rales (51%)
• tachycardia (30-44%)
• elevated neck veins (31%)
• S4 (24%)
• loud S2 (23%)
• cyanosis (11%)
• sweating (11%)
• rhonchi (5%)
• pleural rub (3%)

• increased A-a gradient (75-90%):
  • see under hypoxia
  • normal A-a gradient:
    • in air:
      • < 10mmHg in young adults
      • < 20mmHg in elderly
      • < 4+ age/4 on air (Skorodin)
    • < 10% pIO2
  • A-a gradient = alveolar pO2 - arterial pO2
    • alveolar pO2 = (760-47)xFiO2 - arterial PCO2/R, where R usually = 0.8
    • may be normal in 23% of pts with PE
    • if abnormal, is more likely to be due to other pulmonary pathology rather than PE
    • thus although better than pO2 or pCO2, it has poor predictive value
• pO2:
  • has zero predictive value (as does SaO2)
  • 20% have pO2 > 80mmHg in air & 5% have pO2 > 100mmHg in air
  • in pts with suspected PE (ie. probability of PE ~50%):
    • the incidence of PE is higher in the group with pO2 higher rather than lower than an arbitrary pO2 cutoff value (whether 65, 70 or 80mmHg)
• low pCO2:
  • poor marker - 35% PE's vs 33% no PE!

• abnormal in 70% but non-specific abnormalities due to right heart strain:
• acute PE:
  • ST/T changes (esp. III, V1-2) (49%)
    • see https://lifeinthefastlane.com/ecg-library/100-ecgs/quiz-ecg-007/
  • sinus tachycardia (44%)
  • RBBB (15%)
  • S1Q3T3 (12%)
  • P pulmonale (6%)
  • atrial arrhythmias (2%)
• chronic PE:
  • RAH (7%)
  • RVH (6%)
  • T wave inversion (esp. III, V1-2) (40%) - if T inv. in both ant. & inf. leads this is highly specific for PE (75%) - Marriott
  • pseudoinfarction (11%)

• usually abnormal (84%) but mostly subtle abnormalities:
  • atelectasis or parenchymal abnormality (68%) - may take 3 days to develop
  • pleural effusion (48%)
  • pleural based opacity (35%)
    • eg. Hampton's hump (rare):
      • pleural based density/lung consolidation with a rounded border pointing to hilum
  • elevated hemidiaphragm (30%)
  • reduced pulmonary vasculature (21%)
  • prominent central pulmonary arteries (14%)
    • Westermark's sign (7%)
      • dilated pulmonary outflow tract on side of embolism with area of decreased perfusion distal to it
  • pulmonary oedema (4%, BUT 13% pts without PE had it!!)
• useful in diagnosis of other conditions (eg. pneumonia, APO, pneumothorax)
• if “normal” in setting of hypoxaemia then suggestive of PE

• see Ix of suspected pulmonary embolism (PE)

• PIOPED II study: sens 83% and spec 96% for PE thus positive likelihood ratio (LR) = 0.83/(1-0.96) = 21