Lecture 20 - Diagnosis And Management Of PE

Question 1

Pulmonary embolism

Answer 1

• DVT and PE are manifestations of the same condition: VTE
• may be lethal acutely, or lead to chronic disability
• incidence 100-200 per 100.000/yr
• symptoms are not specific, some patients detected without symptoms
• PE is the cause of death in 5.2% of autopsy series of 6822 patients who died in a single hospital

Question 2

Pathophysiology

Answer 2

• thrombus developing in veins of lower limbs or pelvis -> embolism to pulmonary arteries
• within the veins: Thrombus development - Virchow’s triad. Local effects in calf/legs. Organisation of venous thrombus and risk of recurrent events
• Cardiopulmonary effects: acute effects of embolization: RV, shock. Chronic effects on pulmonary arterial tree

Question 3

Virchow’s triad

Answer 3

• Hypercoagulability (blood): cancers, inflammation (including surgery), thrombophilias, contraceptive pill, pregnancy
• Heamodynamics (Flow): immobility, orthopedic injury/surgery, pregnancy
• endothelial injury/dysfunction (Vessel): trauma, chronic venous disease

Question 4

Acute effects with larger, central emboli

Answer 4

• increased pulmonary vascular resistance
• thin-walled RV has limited ability to acutely adapt: RV dilatation, reduced contractibility, tricuspid regurgitation
• reduced LV filling, reduced CO
• reduced RV coronary perfusion, RV ischaemia
• hypoxaemia from reduced CO, VQ mismatch, right to left shunting through foramen ovale

Question 5

Acute effects: smaller, peripheral emboli

Answer 5

• pulmonary infarction: fever
• hemorrhage: haemoptysis
• pleural irritation/inflammation: pleuritic pain, pleural effusions

Question 6

Chronic effects

Answer 6

• recurrent embolization
• > organisation and incomplete recenalization in pulmonary arterial tree
• > PHT
• > RV failure, cor pulmonale
• > Systemic embolization if there is a right to left shunt (paradoxical embolization)

Question 7

Assessment

Answer 7

• confirm diagnosis or exclude PE

- assess severity: shock or hypotension

Question 8

History

Answer 8

• Resp: Dyspnea, pleuritic pain, haemoptysis
• DVT: limb swelling, pain
• Systemic: fever, syncope
• Risk factors: immobilisation, pregnancy, oral contraception, HRT, prior DVT/PE, chronic venous disease, cancer, family history

Question 9

Examination

Answer 9

• vitals
• resp rub
• cardiac: PHT, RV failure
• CXR: effusion, atelectasis, other diagnosis
• ECG
• blood gases: assessment, not to diagnose
• Other blood tests: creatinine, Hb

Question 10

Assessing pre-test probability

Answer 10

• clinical features insufficient to diagnose PE, but are important to assess pre-test probability
• Clinical prediction rules: Well’s or Geneva score, in combination with d-diner or other imaging

Question 11

If low suspicion of PE: PE Rule Out criteria (PERC)

Answer 11

• no further testing required if all conditions are met

- pretest probability is

Question 12

Simplified Well’s criteria

Answer 12

• one point each for: Previous PE or DVT, HR>100bpm, surgery or immobilisation within the past 4 weeks, haemoptysis, active cancer, clinical signs of DVT, alternative diagnosis less likely than PE
• PE probability low: 0-1
• PE probability intermediate: 2-4
• PE probability high: >5

Question 13

D-diner

Answer 13

• a product of fibrinolysis (indicates clot formation)
• used if pre-test probability is low-intermediate
• only useful if d-diner test is negtive
• not specific, can be elevated with inflammation, cancer, pregnancy

Question 14

Ruling out PE with D-diner

Answer 14

• a low/intermediate pretest pronbability + negative d diner EXCLUDES PE

Question 15

CT pulmonary angiography

Answer 15

• sensitivity 83%, specificity 96%

- always use in context with pre-test probability: be cautious if discordance

Question 16

CTPA

• advantages
• disadvantages

Answer 16

• advantages: rapid, provide information relevant to alternative diagnosis
• disadvantages: risk of contrast-induced renal toxicity (higher with existing renal disease), risk of allergic reaction, radiation exposure

Question 17

VQ scan

Answer 17

• ventilation scan: technetium-99m labelled aerosols or microparticles
• perfusion scan: iv injection of Tc-99m labelled macro-aggregated albumin
• VQ mismatch: no perfusion in areas of normal ventilation

Question 18

VQ

Answer 18

• useful if CT contraindicated
• needs normal CXR
• results may be inconclusive
• exercise caution if result is discordant with pre-test probability

Question 19

Pulmonary angiography

Answer 19

• used as the gold standard for many trials
• percutaneous catherization of pulmonary arterial tree, usually via femoral vein
• also requires radiological contrast
• consider if other tests are not conclusive
• not commonly used to diagnose PE, used to evaluate chronic thromboembolic disease

Question 20

Venous ultrasound

Answer 20

• loot for proximal thrombi: 40-50% progress to PE, sufficient to warrant therapy for VTE
• does not detect pelvic thrombosis
• lack sensitivity
• use if: other testing inconclusive, contraindications to other tests: renal failure, pregnancy

Question 21

Echocardiography

Answer 21

• can be done at the bedside if patient is unstable
• look for RV dilatation/dysfunction, pHT
• not specific
• uses: assess severity, support presence of PE, look for other causes of shock: tamponade

Question 22

Testing vs empiric treatment

Answer 22

• many tests can be done quickly
• if delays are anticipated with confirmatory testing, and suspicion for PE is high, consider empiric anticoagulant therapy

Question 23

Management

Answer 23

• supportive: O2, fluid resuscitation, inotropes, analgesia, monitoring ICU/HDU if unstable
• anticoagulant: heparin, warfarin, new oral anticoagulant
• with shock: thrombolysis

Question 24

General considerations regarding anticoagulation

Answer 24

• facilitate usual mechanism for thrombus resolution (fibrinolysis) and recanalisation
• VTE can be fatal: anticoagulation prevents early death and recurrent symptomatic or fatal VTE
• risk of bleeding: can cause mortality or major morbidity

Question 25

Prognosis from acute PE

Answer 25

• crude mortality 17% at 3 months

- risk factor: age, cancer, CCF, COPD, hypotension, low RR, RV hypokinesis

Question 26

Unfractionated heparin

Answer 26

• given IV
• short half life: can be stopped quickly if needed, or reversed with protamine
• need anticoagulant monitoring: APTT
• risk of heparin induced thrombocytopenia
• preferred if massive or submassive PE

Question 27

LMWH

Answer 27

• given subcutaneously
• longer half life
• predictable dosing: dose based on weight
• caution with renal failure or marked obesity
• anti-coagulant monitoring available, but not needed routinely

Question 28

Warfarin

Answer 28

• oral vit K antagonist
• longer OofA: start with heparin or LMWH
• require blood monitoring: INR, target 2-3
• can be reversed: FFP or vit K
• Diet, liver impairment or other drugs may affect with dosing
• teratogenicity: contraindicated in pregnancy

Question 29

NOAC

Answer 29

• rivaroxaban or apixaban approved for PE in australia:
• can be used as initial treatment or following heparin/ LMWH
• oral, long half life
• fixed dose. Causation with renal impairment
• no practical means to reverse effects, but phase 3 trials suggest lower risk of major bleeding

Question 30

Thrombolysis

Answer 30

• tissue plasminogen activator
• consider thrombolysis in setting of shock or hypotension: these patients have a high risk of in-hospital deaths (massive PE)
• submassive PE: RV dysfunction on echo/CT but without shock or hypotension
• thrombolysis reduced risk of early haemodynamic compromise but with increased risk of major bleeding and no overall effect on mortality

Question 31

Other therapies

Answer 31

• IVC filter placement if anticoagulation is contraindicated
• if hemodynamic compromise develops: surgical embolectomy, percutaneous catheter treatment, fragment or remove thrombus
• VA-ECMO: early experience -> providing cardio-respiratory support while awaiting effect of anticoagulation

Question 32

Approaches

Answer 32

• PE + shock: IV heparin, consider thrombolysis
• otherwise: LMWH/heparin -> warfarin
• LMWH/heparin -> NOAC
• start with NOAC

Question 33

Duration of anticoagulant therapy

Answer 33

• provoked PE: generally 3-6 months anticoagulation
• unprovoked PE: first event: 6 months, consider continuing indefinitely. If second or recurrent event: recommend indefinite anticoagulant
• VTE recurrence risk is low while on anticoagulation
• recurrence rate is higher if PE was unprovoked
• consider bleeding risk vs risks of VTE

Question 34

Aspirin in unprovoked PE

Answer 34

• after ceasing standard anticoagulant, aspirin reduces risk of recurrence
• bleeding risk lower

Question 35

Late complication of PE

Answer 35

• recurrent VTE
• Chronic thromboembolic pulmonary hypertension (CTEPH)
• 0.1-9% incidence within 2 years
• dyspnea, progression to RV dysfunction
• thrombi -> pulmonary vascular
• diagnosed by VQ, CT, confirmed by pulmonary angiography

Question 36

CTEPH management

Answer 36

• anticoagulant
• Surgery: pulmonary endarterectomy
• riociguat: oral stimulator of guanylate cyclase. Improves exercise capacity and pulmonary haemodynamics