Pulmonary embolism

Question 1

Define pulmonary embolism

Answer 1

Pulmonary embolism (PE) is a consequence of thrombus formation within a deep vein of the body –> occluding the pulmonary vasculature

Thrombus formation in the venous system occurs as a result of:

1. venous stasis
2. trauma
3. hypercoagulability

Question 2

What are the 3 factors:

1. venous stasis
2. trauma
3. hypercoagulability

collectively known as?

Answer 2

Virchow’s triad

Question 3

Approx what % of deep venous thrombi will embolise to the pulmonary vasculature, resulting in a PE?

Answer 3

Approx. 51%

Question 4

Where is the most common site of venous thrombus formation?

Answer 4

lower extremities.

Question 5

What is venous thromboembolic disease?

Answer 5

The preferred term to describe the spectrum of disease

• beginning with the risk factors of Virchow’s triad
• progressing to deep venous thrombosis
• resulting in life-threatening PE

Question 6

What may be the consequences of a PE if it is not aggresively treated?

Answer 6

• RHF
• cardiac arrest

Question 7

What is the aetiology of pulmonary embolism

Answer 7

Virchow’s triad:

1. venous stasis
2. trauma (vessel wall damage)
3. hypercoagability

Venous stasis:

• poor blood flow and stasis promote the formation of thrombi.
• Venous stasis and congestion result in valvular damage, further promoting thrombus formation.

Vessel wall damage:

• endothelial cell damage promotes thrombus formation, usually at the venous valves.

Hypercoagulability:

• a number of other conditions (both inherited and acquired) increase the risk of PE.

Question 8

Which factors/conditions are associated with venous stasis?

Answer 8

• age >40 years
• immobility
• general anaesthesia
• paralysis
• spinal cord injury
• MI
• prior stroke
• varicose veins
• advanced congestive heart failure
• advanced COPD.

Question 9

What are the insults that can cause venous vessel wall damage?

Answer 9

• trauma
• previous DVT
• surgery
• venous harvest
• central venous catheterisation

Question 10

Do venous thrombi occur de novo in the pulmonary vasculature?

Answer 10

rarely

• Clots usually form in the deep venous system of the lower extremities and embolise.

Question 11

Why might a PE cause RHF?

Answer 11

• PE occurs when a thrombus dislodges and becomes trapped in the pulmonary vasculature.
• This obstruction increases pulmonary vascular resistance (PVR), increasing the work of the right ventricle.
• The right ventricle compensates by increasing heart rate using the Frank-Starling preload reserve via dilation.
• Further increases in PVR overcome the right ventricular (RV) compensatory mechanisms, leading to over-distension of the right ventricle, increased RV end-diastolic pressure, and decreased RV cardiac output.
• Decreased RV output leads to decreased left ventricular (LV) preload.
• As left ventricle filling and cardiac output decrease, lowered mean arterial pressure progresses to hypotension and shock. In previously healthy individuals, this can occur when as little as 50% of the pulmonary vasculature is occluded.

Question 12

What do DVTs consist of?

Answer 12

DVTs are composed mainly of fibrin and entrapped erythrocytes (red clots)

• Unlike platelet-rich arterial thrombi

Hence endothelial damage appears to be less important in DVT than in arterial thrombosis.

Although platelet aggregation is seen, it is not evident at the site of thrombus attachment, suggesting that activation of the coagulation cascade precedes platelet activation

Question 13

Recall the coagulation cascade

Answer 13

Question 14

Recall how platelets are activated

Answer 14

Question 15

Which conditions (both inherited and acquired) increase the risk of hypercoagulability?

Answer 15

• cancer
• high-oestrogen states (oral contraceptives, hormone replacement, obesity, pregnancy)
• IBD
• nephrotic syndrome
• sepsis
• blood transfusion
• inherited thrombophilia (factor V Leiden mutation, prothrombin gene mutation, protein C and S deficiency, antithrombin deficiency, and antiphospholipid antibody syndrome).

Question 16

What are the strong risk factors of pulmonary embolism?

Answer 16

PMH

• cancer
  
  • multiple myeloma, brain and pancreatic cancer = highest RR
  • lung, colon, and prostate cancer = most episodes
• Recent surgery or hospitalisation
  
  • Lower limb fractures and joint replacements = strongest provoking factors
• Previous or current DVT
  • present in 25% pts with PE
• Pregnancy and 6 weeks postpartum
  
  • = 4x risk of thrombosis during pregnancy
  • = 60x risk after pregnany vs non-pregnant women

SH

• History of immobilisation

Question 17

What are the weak risk factors for a PE?

Answer 17

PMH

• Other significant medical comorbidities
  
  • e.g. congestive heart failure, COPD, concurrent sepsis
• Obesity
• increasing age
• varicose veins
• Known thrombophilias
• other
  
  • ​Central vein catheter, Nephrotic syndrome, Chronic dialysis, Myeloproliferative disorders, Paroxysmal nocturnal haemoglobinuria, Behcet’s disease, Blood transfusion

SH

• Long-distance travel
• Smoking

DH

• Combined oral contraceptive pill
• HRT

FH

• 1st-degree relative with a history of confirmed PE or DVT

Question 18

What % of PEs occur with no underlying risk factors?

Answer 18

30% of cases

can be spontaneous

Question 19

Summarise the epidemiology of pulmonary embolism

Answer 19

• UK: 47,594 cases of PE were reported in the 1-year period between 2013 and 2014
• higher in older age groups

Question 20

What are the symptoms of pulmonary embolism?

Answer 20

• dyspnoea
• peuritic chest pain
  
  • acute onset
  • ​localised to one side of the chest
  • unlikely to be central
  • (caused by pleural irritation due to distal emboli causing pulmonary infarction)
• cough
• pain & swelling leg
  
  • ​commonly 1 leg, although both legs may be affected

uncommon

• fever
• haemoptysis
  
  • ​ensure it is true, and not originating from elsewhere

Question 21

What is the nature of onset of PE symptoms?

Answer 21

acutely rather than gradually

Question 22

What are the signs of pulmonary embolism o/e?

Answer 22

• tachypnoea
• hypoxaemia
  
  • Oxygen saturations <94%
  • but only presents in 60% of cases
• creps O/A
  
  • ​explains cough

• There may also be evidence of a concurrent DVT*
• UNCOMMON: signs of shock/hypotension or severely reduced haemodynamic reserve*

Question 23

What are the signs of shock/hypotension or severely reduced haemodynamic reserve?

Answer 23

shock:

• altered cognition
• cool extremities
• mottled or ashen skin
• slow capillary refill
• oliguria.

Question 24

What score is used to assess the risk of PE?

Answer 24

Wells score

• used to assess the likelihood of a PE in any non-pregnant patient who is haemodynamically stable

Question 25

What are the criteria for the Wells score?

And how many points does each criterion receive?

Answer 25

Question 26

How is the Well’s score interpreted?

Answer 26

This will categorise the patient into either

• ‘PE likely’ (Wells score >4)
• ‘PE unlikely’ (Wells score ≤4)

Question 27

1. While signs of RHF may be uncommon, what are they?
2. And what do they imply?

Answer 27

1. Hypotension, syncope, tachycardia
2. high-risk PE with a larger clot burden and a higher mortality rate

Question 28

How does the Well’s score guide Tx and investigations?

Answer 28

If a patient has a ‘PE likely’ Wells (or Geneva) score:

• start anticoagulation
• arrange investigation with definitive imaging (CTPA if available)

If a patient has a ‘PE unlikely’ Wells (or Geneva) score:

• order a D-dimer unless pt fulfils all Pulmonary Embolism Rule-Out Criteria
  
  • (in which case a PE can be effectively ruled out and no further investigations are indicated)

Question 29

What is the Pulmonary Embolism Rule-Out Criteria?

Answer 29

Apply PERC to any patient classified as ‘PE unlikely’ based on Wells (or Geneva) score.

No further investigation is indicated if a patient meets all the PERC criteria (a PE can effectively be ruled out).

• The risk for PE is considered to be lower than the risk of testing.

Request D-dimer testing for any patient in whom the PERC criteria fail to rule out a PE (i.e., one of more criterion not fulfilled).

The PERC criteria are:

• Age <50 years
• Heart rate <100 bpm
• SaO2 on room air ≥95%
• No unilateral leg swelling
• No haemoptysis
• No recent surgery or trauma (≤4 weeks ago requiring treatment with general anaesthesia)
• No prior PE or DVT
• No hormone use (oral contraceptives, hormone replacement, or oestrogenic hormones use in male or female patients).

Question 30

What are the primary investigations for ?pulmonary embolism?

Answer 30

imaging

• CT pulmonary angiography (CTPA)
  
  • = definitive
  • PE is confirmed by direct visualisation of thrombus in a pulmonary artery
  • might also show signs of RVH
• echocardiogram
  
  • for haemodynamically unstable patients who cannot have CTPA
  • Do not use echocardiography routinely in haemodynamically stable patients with suspected PE
  • mobile right heart thrombi can be detected by transthoracic or transoesophageal echocardiography
  • will also show RVH and RVF
• ECG
  
  • ​not diagnostic of PE
  • excludes other causes
  • Can indicate RV strain suggestive of PE

bloods

• D dimer
  
  • ​elevated (>500 ng/mL)
• FBC
  
  • May indicate thrombocytopenia or anaemia. These patients are at an increased risk of complications from bleeding when taking an anticoagulant
  • May also indicate thrombocythaemia or polycythaemia which increase the risk of venous thromboembolism (VTE).
• U&Es
  
  • ​Checks baseline renal function
  • for prescription of some anticoagulants e.g. low molecular weight heparin, fondaparinux, apixaban, rivaroxaban, dabigatran (should be used carefully in those with renal impairment)
• coagulation studies: PT, INR, aPTT
  
  • ​needed to establish baseline values before starting anticoagulation
• LFTs
  
  • Abnormal LFTs can influence the choice of anticoagulation.

Question 31

What is D dimer?

Answer 31

• fibrin degradation product
• a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis

indictes presence of a thrombus/clot

Question 32

When might a CTPA be contraindicated?

Answer 32

• pregnant
• young
• renal impairment
• contrast allergy

–> use echo instead

Question 33

What are some possible secondary investigations to be considered when suspecting a PE?

Answer 33

ABG

• Do not perform an ABG if the oxygen saturations are within normal range on room air
• might show hypoxaemia and hypocapnia suggestive of PE

CXR

• usually normal (hence is used to exclude other causes)
• but may show atelectasis
• pleural effusion elevation of hemidiaphragm can be suggestive of a PE

lower limb compression venous US

• to investigate patients suspected of having a concurrent DVT
• might show inability to fully compress lumen of vein using US transducer

cardiac biomarkers - high sensitivity troponin (either I or T), NT-proBNP or BNP

• not used in diagnosing PE
• But can aid prognostic assessment (higher = worse prognosis)
• Do not use routinely to risk stratify patients.

ventilation-perfusion (V/Q) scan

• can be performed in patients with an elevated D-dimer and a contraindication to CTPA
• PE likely when an area of ventilation is not perfused

Question 34

Name some emerging investigations for PE

Answer 34

Question 35

What is the management pathway of pulmonary embolism?

Answer 35

reperfusion therapy=

• Systemic thrombolysis is the standard treatment of choice.
• Do not allow supportive therapy to delay thrombolysis, which may quickly restore haemodynamic stability.
• Use vasoactive drugs if SBP remains <90 mmHg after thrombolysis and adequate fluid resuscitation.

Question 36

What is the management pathway of pulmonary embolism in haemodynamically unstable patients?

Answer 36

Haemodynamically unstable patients require:

• immediate primary reperfusion (usually thrombolysis)
• anticoagulation
• supportive care

Ongoing anticoagulation therapy is indicated to reduce the risk of recurrent events or fatal PE.

Question 37

Name some complications of pulmonary embolism

Answer 37

Question 38

What is heparin induced thrombocytopenia (HIT)?

Answer 38

HIT is an adverse immune-mediated drug reaction that leads to the formation of IgG antibodies against heparin-platelet factor IV complexes.

The incidence of HIT (following a minimum of 4 days heparin exposure) is believed to be between 0.1% and 1% in medical patients receiving prophylactic or therapeutic doses of heparin. In patients with cancer, the incidence may be 1%.

Risk factors include (but are not limited to):

• duration and type of heparin exposure
• patient population
• severity of trauma
• gender - women have approximately twice the risk of developing HIT as men.

The incidence can be minimised by use of a low molecular weight heparin or fondaparinux.

Clinical prediction rules to assist physicians with determining the probability that a patient has HIT have been developed

Question 39

What is the prognosis of pulmonary embolism?

Answer 39

The Pulmonary Embolism Severity Index (PESI) and simplified Pulmonary Embolism Severity Index (sPESI) classify patients with confirmed PE without shock or hypotension into categories associated with increasing 30-day mortality.

• Using sPESI, patients in the high-risk category have a short-term mortality of 10.9%
• while patients in the low-risk category have 30-day mortality of 1%.

Mortality is often due to cardiogenic shock secondary to right ventricular (RV) collapse (precipitated by RV dysfunction)