Pulmonary Embolism (PE)

📋 Key Information Summary

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Pulmonary embolism (PE) affects approximately 8,000–10,000 Australians annually; incidence increases with age and is higher in Aboriginal and Torres Strait Islander populations.
Use the Wells score to stratify pre-test probability; apply the PERC rule to safely exclude PE in low-risk emergency presentations without requiring D-dimer testing.
D-dimer has high sensitivity but low specificity; age-adjusted cutoffs (age × 10 µg/L for patients >50 years) improve diagnostic utility and reduce unnecessary imaging.
CT pulmonary angiography (CTPA) is the first-line imaging modality; V/Q scanning is the preferred alternative when CTPA is contraindicated (contrast allergy, severe renal impairment, pregnancy).
Hemodynamic classification into massive (with shock), submassive (RV dysfunction without shock), and low-risk PE guides treatment intensity and escalation pathways.
Systemic anticoagulation with LMWH (enoxaparin 1 mg/kg SC BD) or UFH IV infusion is the immediate treatment for non-massive PE; DOACs (apixaban, rivaroxaban) can be initiated as first-line oral therapy.
Systemic thrombolysis (alteplase 100 mg IV over 2 hours) is indicated for massive PE with haemodynamic instability; catheter-directed therapy is an alternative for patients with contraindications to systemic lysis.
Submassive PE with signs of clinical deterioration warrants multidisciplinary discussion regarding escalation to thrombolysis or catheter-directed therapy.
Anticoagulation duration: minimum 3 months for provoked PE; ≥6 months (often extended/indefinite) for unprovoked PE guided by bleeding risk assessment using HAS-BLED or VTE-BLEED scores.
All patients with PE should be screened for chronic thromboembolic pulmonary hypertension (CTEPH) at 3–6 months if dyspnoea persists; echocardiography is the initial screening tool.
DOACs are generally preferred over warfarin for long-term anticoagulation due to convenience, predictable pharmacokinetics, and comparable or superior safety profiles (Hokusai-VTE, EINSTEIN trials).
Beware of PE in Aboriginal and Torres Strait Islander patients presenting with acute breathlessness; address geographic barriers to CTPA access, consider point-of-care D-dimer, and facilitate telemedicine-guided management in remote settings.

Introduction & Australian Epidemiology

Pulmonary embolism (PE) is a potentially life-threatening condition caused by obstruction of the pulmonary arterial vasculature, most commonly by thrombus originating from the deep veins of the lower extremities or pelvis. PE and deep vein thrombosis (DVT) together constitute venous thromboembolism (VTE), which represents a significant cause of morbidity and mortality in Australia.

In Australia, VTE accounts for an estimated 8,000–10,000 hospital admissions per year, with PE responsible for approximately 3,000 deaths annually. The incidence of VTE in Australia is estimated at 0.8–1.6 per 1,000 person-years, rising sharply with age to exceed 5 per 1,000 person-years in those over 80 years. The Australian Institute of Health and Welfare (AIHW) data indicate that PE-related hospital separations have increased over the past decade, partly reflecting improved detection with modern imaging.

Key Australian epidemiological considerations include:

Age distribution: Median age at diagnosis is approximately 63 years; rarely seen in children except in the context of central venous catheters, malignancy, or inherited thrombophilia.
Sex differences: Slightly higher incidence in males overall, though females have additional risk factors including combined oral contraceptive use, hormone replacement therapy, and pregnancy.
Indigenous health disparities: Aboriginal and Torres Strait Islander Australians experience higher rates of VTE, particularly in remote communities, driven by higher prevalence of comorbidities including rheumatic heart disease, obesity, diabetes, and limited access to thromboprophylaxis.
Rural and remote access: Geographic isolation poses challenges for timely diagnosis (limited CTPA availability) and specialist input; transfer to tertiary centres may be required for massive PE management.
Hospital-acquired VTE: Approximately 50–60% of hospital-associated VTE events are considered preventable with appropriate thromboprophylaxis, as emphasised by the National Safety and Quality Health Service (NSQHS) Standards.

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NSQHS VTE Prevention Standard: All Australian hospitals accredited under NSQHS Standards are required to implement VTE risk assessment and thromboprophylaxis protocols for every admitted patient. Failure to provide appropriate prophylaxis constitutes a quality-of-care concern.

Diagnosis & Risk Stratification

Clinical Decision Rules: Wells Score

The Wells score for PE is the most widely validated clinical prediction rule and should be applied to all patients presenting with suspected PE. It stratifies patients into low, moderate, or high pre-test probability categories, guiding subsequent diagnostic testing.

Criterion	Points
Clinical signs/symptoms of DVT (leg swelling, palpable deep vein tenderness)	3
PE is the #1 diagnosis, or equally likely	3
Heart rate > 100 bpm	1.5
Immobilisation (≥3 days) or surgery within the past 4 weeks	1.5
Previous DVT/PE	1.5
Haemoptysis	1
Active malignancy (treatment within 6 months or palliative)	1

Score	Probability	Prevalence of PE	Next Step
0–4 (or <5)	Low / PE-unlikely	~3–8%	Apply PERC rule or D-dimer
≥5 (or ≥6 if two-level)	High / PE-likely	~35–50%	Proceed directly to CTPA

PERC Rule (Pulmonary Embolism Rule-out Criteria)

The PERC rule is applied only to patients classified as low risk by Wells score. If all 8 PERC criteria are negative, PE can be safely excluded without D-dimer testing, avoiding unnecessary imaging.

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PERC criteria (all must be negative): Age <50 years · Heart rate <100 bpm · SpO₂ ≥95% on room air · No haemoptysis · No exogenous oestrogen use · No prior DVT/PE · No unilateral leg swelling · No surgery/trauma within 4 weeks. If any criterion is positive → proceed to D-dimer testing.

D-Dimer Interpretation

D-dimer (fibrin degradation product) testing is highly sensitive (~95%) but poorly specific (~40–50%) for PE. It is most useful for excluding PE in low-to-moderate probability patients.

Standard cutoff: 500 µg/L (FEU) — a negative result in a low-risk patient effectively excludes PE (NPV >99%).
Age-adjusted cutoff (patients >50 years): Age × 10 µg/L (e.g., cutoff for a 65-year-old = 650 µg/L). This strategy reduces false positives and unnecessary CTPA in older adults. Validated in the ADJUST-PE study.
Limitations: D-dimer is elevated in malignancy, infection, pregnancy, recent surgery, inflammation, liver disease, and advanced age — it should not be used to exclude PE in high-risk patients regardless of the result.
Availability: Available at all Australian public hospital laboratories; point-of-care D-dimer assays are increasingly available in rural EDs but vary in sensitivity.

CT Pulmonary Angiography (CTPA)

CTPA is the gold-standard first-line imaging modality for PE diagnosis in the Australian setting. Modern multidetector CT scanners achieve sensitivity of ~97–100% and specificity of ~97% for PE in the main, lobar, and segmental pulmonary arteries.

MBS item: MBS item 57355 (CT angiography, chest). Requires a valid clinical request from a medical practitioner.
Contrast considerations: IV iodinated contrast is required. Assess renal function (eGFR) prior; avoid if eGFR <30 mL/min/1.73 m² unless benefits outweigh risks. Premedicate patients with prior contrast reactions.
Radiation: Estimated effective dose 3–5 mSv. Use judiciously in young women (mammary tissue irradiation) and during pregnancy (low-dose protocols available).
Availability: Available 24/7 in major metropolitan hospitals; limited after-hours availability in some regional centres — may require patient transfer.

V/Q (Ventilation-Perfusion) Scanning

V/Q scanning is the preferred alternative to CTPA when iodinated contrast is contraindicated (severe contrast allergy, significant renal impairment) or in selected pregnancy cases. A normal V/Q scan effectively excludes PE; a high-probability scan is diagnostic. However, the majority of V/Q scans yield intermediate or low-probability results, which are non-diagnostic.

MBS item: MBS item 61358 (nuclear medicine, pulmonary perfusion study).
Technetium-99m macroaggregated albumin (⁹⁹ᵐTc-MAA) is used for perfusion; ventilation agents include ⁹⁹ᵐTc-DTPA aerosol or ⁸¹ᵐKr gas.
SPECT V/Q: Single-photon emission CT V/Q has improved sensitivity over planar imaging and is increasingly available in Australian nuclear medicine departments.
Limitations: Less specific than CTPA; inferior diagnostic performance in patients with pre-existing lung disease (COPD, pneumonia). Requires nuclear medicine facilities — not universally available in smaller regional hospitals.

Diagnostic Algorithm

1

Clinical Suspicion

Patient presents with acute dyspnoea, pleuritic chest pain, tachycardia, or haemoptysis. Apply Wells score.

2

Low Probability (Wells ≤4)

Apply PERC. If PERC-negative → PE excluded. If PERC-positive → D-dimer. If D-dimer negative → PE excluded. If D-dimer positive → CTPA.

3

High Probability (Wells ≥5)

Proceed directly to CTPA. Do NOT delay with D-dimer testing. If CTPA unavailable → empirical anticoagulation and urgent transfer.

4

CTPA Contraindicated

V/Q scan (or SPECT V/Q). If non-diagnostic → lower-limb compression ultrasound for DVT → if positive, treat; if negative, consider pulmonary angiography (rarely needed).

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Critical safety point: In a haemodynamically unstable patient with high clinical suspicion for massive PE, do NOT delay treatment for imaging. Initiate empirical anticoagulation (UFH bolus), arrange emergent CTPA or bedside echocardiography, and activate the massive PE protocol.

Additional Investigations

Essential ECG Sinus tachycardia most common. S1Q3T3 pattern (sensitivity ~20%). Right heart strain: right axis deviation, RBBB, T-wave inversion V1–V4, P-pulmonale. Useful to exclude differential (STEMI, pericarditis).

Essential Troponin Elevated in 30–50% of acute PE (myocardial stretch/necrosis). High-sensitivity troponin (hs-cTnT or hs-cTnI) provides prognostic value — elevated troponin in submassive PE indicates higher mortality risk.

Essential NT-proBNP / BNP Elevated in RV dysfunction. Combined with troponin and imaging for risk stratification. BNP >100 pg/mL or NT-proBNP >600 pg/mL associated with worse prognosis.

Available Echocardiography Bedside echo in unstable patients may show RV dilation, RV/LV ratio >1.0, septal bowing, tricuspid regurgitation. McConnell's sign (RV free wall hypokinesis with apical sparing) is suggestive. Formal TTE for prognostic assessment in confirmed PE.

Available Lower-limb venous compression ultrasound Detects proximal DVT (femoral, popliteal). A positive result in the context of suspected PE confirms VTE and supports anticoagulation. Compression ultrasound has sensitivity ~90% for proximal DVT.

Specialist CTPA with RV/LV ratio measurement RV/LV ratio >0.9 on CTPA is a marker of RV dysfunction and is used for submassive PE risk stratification. Should be reported routinely by radiologists.

Acute PE Management

Hemodynamic Classification

The European Society of Cardiology (ESC) haemodynamic classification, widely adopted in Australian practice, stratifies acute PE into three categories that directly guide management intensity:

Low Risk

Haemodynamically Stable PE

SBP ≥90 mmHg, no RV dysfunction on imaging or biomarkers. Mortality <1%. No signs of shock or hypoperfusion.

Setting: Ward-based care, early discharge considered

Submassive (Intermediate-High)

Stable with RV Dysfunction

SBP ≥90 mmHg BUT imaging (echo/CTPA) shows RV dysfunction AND elevated biomarkers (troponin or BNP). Mortality 3–15%. Close monitoring required.

Setting: HDU / step-down unit

Massive (High Risk)

Haemodynamic Instability

SBP <90 mmHg for ≥15 min or requiring vasopressors, cardiac arrest, or obstructive shock. Mortality 25–65%. Immediate escalation required.

Setting: ICU / Cath lab — immediate thrombolysis or embolectomy

Initial Anticoagulation

Anticoagulation should be initiated as soon as PE is diagnosed (or strongly suspected) in the absence of absolute contraindications. The goal is to prevent thrombus propagation and recurrent embolisation while endogenous fibrinolytic mechanisms resolve the existing burden.

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Enoxaparin (LMWH)

Clexane® · Low-molecular-weight heparin

Adult dose 1 mg/kg SC every 12 hours (twice-daily regimen preferred in Australia)

Paediatric dose Age <2 months: 1.5 mg/kg SC BD; Age ≥2 months: 1 mg/kg SC BD

Renal adjustment eGFR <30 mL/min: 1 mg/kg SC once daily (or dose-reduce). Monitor anti-Xa levels.

Hepatic adjustment Use with caution; monitor anti-Xa levels. Avoid in severe hepatic impairment with coagulopathy.

PBS status ✔ PBS General Benefit

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Unfractionated Heparin (UFH)

Heparin sodium · Parenteral anticoagulant

Adult dose Bolus 80 units/kg IV, then 18 units/kg/hr infusion. Target aPTT 1.5–2.5 × control (laboratory-specific). Monitored by aPTT every 6 hours until therapeutic.

Indications Massive PE (allows rapid reversal with protamine). Renal impairment (eGFR <30). Pre-thrombolysis. Patients who may require urgent procedures.

Renal adjustment Not renally cleared — preferred over LMWH in severe renal impairment.

PBS status ✔ PBS General Benefit

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Apixaban (DOAC)

Eliquis® · Factor Xa inhibitor · Direct oral anticoagulant

Acute dose 10 mg PO BD for 7 days, then 5 mg PO BD (standard long-term dose)

Extended dose 2.5 mg PO BD for extended secondary prevention (after ≥6 months initial treatment)

Renal adjustment CrCl <25 mL/min: use with caution; no PBS authority for eGFR <15 mL/min. Dose-reduce to 2.5 mg BD if ≥2 of: age ≥80, weight ≤60 kg, Cr ≥133 µmol/L.

PBS status ⚠️ PBS Authority Required

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Rivaroxaban (DOAC)

Xarelto® · Factor Xa inhibitor · Direct oral anticoagulant

Acute dose 15 mg PO BD with food for 21 days, then 20 mg PO once daily with food

Extended dose 10 mg PO once daily for extended secondary prevention (after ≥6 months treatment)

Renal adjustment eGFR 15–49: use with caution (15 mg BD then 15 mg OD recommended). Avoid if eGFR <15 mL/min.

PBS status ⚠️ PBS Authority Required

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Warfarin

Marevan® · Coumarin anticoagulant · Vitamin K antagonist

Adult dose Initiate at 5 mg PO daily (2.5 mg in elderly, low body weight, hepatic impairment). Titrate to INR 2.0–3.0. Overlap with LMWH/UFH for ≥5 days AND until INR ≥2.0 for ≥24 hours.

Renal adjustment No renal dose adjustment required. Monitor INR more frequently in renal impairment due to bleeding risk.

PBS status ✔ PBS General Benefit

Anticoagulation Pathway: DOACs vs LMWH → Warfarin

In Australian practice, the preferred approach for acute PE anticoagulation depends on clinical stability, renal function, and patient factors:

Haemodynamically stable, low-risk PE: Initiate a DOAC directly (apixaban 10 mg BD × 7 days then 5 mg BD; or rivaroxaban 15 mg BD × 21 days then 20 mg OD). No need for initial LMWH/UFH bridge. Supported by AMPLIFY and EINSTEIN-PE trials. This is the preferred pathway for most patients and allows early discharge.
LMWH → warfarin pathway: Use when DOACs are contraindicated (antiphospholipid syndrome with triple positivity, mechanical heart valve, severe renal impairment eGFR <15, drug interactions). Start warfarin on day 1 with LMWH; continue LMWH for ≥5 days and until INR ≥2.0 for ≥24 hours.
Massive/submassive PE: Initiate UFH IV bolus + infusion. Transition to DOAC or LMWH → warfarin once stable. UFH is preferred as it is rapidly reversible with protamine and has a short half-life.
Cancer-associated PE: LMWH (dalteparin 200 IU/kg SC OD × 1 month, then 150 IU/kg SC OD) or DOACs (edoxaban, apixaban per CARAVAGGIO, ADAM-VTE trials). Caution with GI malignancy due to increased GI bleeding with DOACs.

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DOACs — Contraindications and cautions: Do NOT use DOACs in antiphospholipid syndrome (triple-positive), mechanical prosthetic heart valves, or pregnancy. Be alert for drug interactions: azole antifungals, rifampicin, HIV protease inhibitors, carbamazepine, phenytoin, and St John's wort significantly affect DOAC levels.

Thrombolysis Indications in Acute PE

Systemic thrombolysis is indicated for the following:

Absolute indication: Massive PE with haemodynamic instability (SBP <90 mmHg ≥15 min, vasopressor requirement, cardiac arrest).
Relative indication: Submassive PE with clinical deterioration — worsening RV function, rising biomarkers, haemodynamic trajectory toward shock, severe hypoxaemia despite supplemental oxygen.
Cardiac arrest with suspected PE: Empirical thrombolysis should be considered during CPR. Alteplase 50 mg IV bolus during cardiac arrest (repeat once if no ROSC).

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Alteplase (tPA)

Actilyse® · Thrombolytic agent

Adult dose (massive PE) 100 mg IV infusion over 2 hours (preferred). OR 0.6 mg/kg over 15 min (max 50 mg) for rapid infusion in extremis.

Cardiac arrest dose 50 mg IV bolus (consider repeat ×1 if no ROSC after 15 min)

Renal adjustment No adjustment required

PBS status ✔ PBS General Benefit

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Thrombolysis — Absolute contraindications: Active internal bleeding · History of haemorrhagic stroke · Ischaemic stroke within 3 months · Intracranial neoplasm · Suspected aortic dissection · Significant head/facial trauma within 3 months · Bleeding diathesis (INR >1.7, platelets <100 × 10⁹/L). Relative contraindications include major surgery within 3 weeks, pregnancy, uncontrolled hypertension (SBP >180), and recent non-compressible vascular puncture.

Massive & Submassive PE

Massive PE (High-Risk)

Massive PE is defined by haemodynamic instability: sustained hypotension (SBP <90 mmHg for ≥15 minutes or requiring inotropic support), pulselessness, or persistent profound bradycardia (HR <40 bpm with signs of shock). In-hospital mortality ranges from 25–65% if untreated.

1

Immediate Resuscitation

IV crystalloid bolus (cautious — excessive fluid worsens RV failure). Noradrenaline infusion for vasopressor support. High-flow oxygen. Avoid excessive positive-pressure ventilation.

2

Anticoagulation

UFH bolus 80 units/kg IV, then 18 units/kg/hr. Do NOT delay for imaging if clinical suspicion is high.

3

Systemic Thrombolysis

Alteplase 100 mg IV over 2 hours. In cardiac arrest: 50 mg IV bolus. This is the first-line reperfusion strategy for massive PE.

4

Escalation if Thrombolysis Fails or Contraindicated

Catheter-directed therapy or surgical pulmonary embolectomy. Consider ECMO as bridging support.

Catheter-Directed Therapy (CDT)

Catheter-directed therapy is an emerging option for patients with massive or submassive PE who have contraindications to systemic thrombolysis or who have failed systemic lysis. CDT includes catheter-directed thrombolysis (low-dose alteplase via pulmonary artery catheter), mechanical thrombectomy, and aspiration thrombectomy devices (FlowTriever, Indigo, EKOS ultrasound-assisted thrombolysis).

Advantages: Lower systemic thrombolytic dose (reduced bleeding risk), direct clot delivery, mechanical disruption of thrombus.
Evidence: SEATTLE-II, FLARE, and OPTALYSE trials demonstrated improvement in RV/LV ratio and pulmonary artery pressure with acceptable safety profiles.
Availability in Australia: Performed at select tertiary centres (Royal Melbourne, Royal Prince Alfred, Royal Adelaide, Princess Alexandra, Fiona Stanley). Requires interventional radiology or cardiology expertise. Available on a case-by-case basis in 2024.
MBS: No dedicated MBS item for catheter-directed PE therapy; costs may be covered under hospital casemix funding or compassionate access programs.

Surgical Pulmonary Embolectomy

Surgical embolectomy is reserved for patients with massive PE when thrombolysis is contraindicated or has failed, and catheter-directed therapy is not available or appropriate.

Procedure: Median sternotomy, cardiopulmonary bypass (CPB), pulmonary arteriotomy with direct clot extraction.
Outcomes: Operative mortality 20–30% in contemporary series (improved from historical rates). Best outcomes when performed before the onset of multiorgan failure.
Centres: Cardiac surgical centres with cardiothoracic surgery capability (most major Australian tertiary hospitals).

Extracorporeal Membrane Oxygenation (ECMO)

Veno-arterial (VA) ECMO may be used as a bridging strategy in patients with massive PE and refractory cardiogenic shock or cardiac arrest, to provide circulatory and respiratory support while definitive reperfusion (thrombolysis, CDT, or embolectomy) is arranged.

Indications: Refractory cardiogenic shock despite maximal medical therapy · Cardiac arrest with suspected PE · Bridge to surgical embolectomy in centres with cardiac surgery.
Complications: Bleeding (systemic anticoagulation required), limb ischaemia, stroke, circuit thrombosis, sepsis.
Australian ECMO centres: Alfred Hospital (Melbourne), Royal Melbourne, Royal Prince Alfred (Sydney), St Vincent's (Sydney), Princess Alexandra (Brisbane), Royal Adelaide, Fiona Stanley (Perth).

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Submassive PE — The difficult middle ground: Patients with submassive PE (stable but RV dysfunction + biomarker elevation) require close monitoring. Early clinical deterioration (worsening tachycardia, falling blood pressure, increasing oxygen requirements, rising lactate) should prompt urgent multidisciplinary discussion regarding escalation to thrombolysis or CDT. The Bova score or sPESI score may help further risk-stratify intermediate-risk patients.

Submassive PE Risk Stratification Scores

Score	Components	Use
sPESI (Simplified PE Severity Index)	Age >80, cancer, chronic cardiopulmonary disease, HR ≥110, SBP <100, SpO₂ <90%	Identifies low-risk patients safe for outpatient management (sPESI = 0)
Bova Score	SBP 90–100 (2 pts), troponin elevated (2 pts), RV dysfunction (2 pts), HR ≥110 (1 pt)	Substratifies intermediate-risk PE; Stage III (≥5 pts) identifies highest-risk patients
HESTIA Criteria	11 clinical criteria for outpatient PE management eligibility	Safe selection of patients for home treatment of low-risk PE

Long-term Anticoagulation

Duration Decisions: Provoked vs Unprovoked PE

The duration of anticoagulation following acute PE is determined by the balance between the risk of VTE recurrence and the risk of major bleeding. The key determinant is whether a transient, reversible provoking factor was identified.

Category	Examples	Recommended Duration	Recurrence Risk (off anticoagulation)
Major provoked (transient risk factor)	Surgery, plaster cast, hospitalisation ≥3 days, major trauma within 3 months	3 months (stop)	~3% at 1 year
Minor provoked	OCP/HRT, long-haul travel (>8 hours), minor surgery, pregnancy	3–6 months (individualise)	~5% at 1 year
Unprovoked (no identifiable trigger)	Idiopathic, or associated with minor/non-persistent risk factors only	≥6 months, consider extended/indefinite therapy	~10–15% at 1 year; ~30% at 5 years
Cancer-associated	Active malignancy (diagnosis, treatment, or palliative)	Extended (indefinite) until cancer resolved or treatment complete	~20% at 1 year
Recurrent VTE	Second or subsequent unprovoked VTE	Extended/indefinite (strongly recommended)	~30–50% at 5 years

Extended Therapy: DOAC Selection

For patients requiring extended (indefinite) anticoagulation, DOACs are generally preferred over warfarin due to their convenience (no INR monitoring), predictable pharmacokinetics, favourable food/drug interaction profiles, and comparable or superior safety data.

Apixaban 5 mg BD → 2.5 mg BD for extended prevention: The AMPLIFY-EXT trial demonstrated that apixaban 2.5 mg BD reduced recurrent VTE by 80% compared with placebo, with no significant increase in major bleeding. This is the preferred extended regimen in many Australian centres.
Rivaroxaban 20 mg OD → 10 mg OD for extended prevention: EINSTEIN-CHOICE showed rivaroxaban 10 mg OD was superior to placebo and comparable to 20 mg OD for preventing recurrence, with lower bleeding risk.
Warfarin (INR 2.0–3.0): Remains appropriate for patients with antiphospholipid syndrome, mechanical heart valves, or those who prefer it. Requires regular INR monitoring (at least monthly at steady state); target TTR (time in therapeutic range) >65%.

Bleeding Risk Assessment

Before committing to extended anticoagulation, bleeding risk must be formally assessed. Two validated scores are commonly used:

HAS-BLED Score

Hypertension (uncontrolled, SBP >160) · Abnormal renal/liver function (1 pt each) · Stroke · Bleeding history · Labile INR (TTR <60%) · Elderly (>65) · Drugs/alcohol (1 pt each). Score ≥3 = high bleeding risk. Requires careful review of modifiable risk factors.

VTE-BLEED Score

Specifically validated for VTE patients on extended anticoagulation. Components: active cancer (2 pts), male with uncontrolled hypertension (1 pt), anaemia (1.5 pts), bleeding history (1.5 pts), age ≥60 (1.5 pts), renal insufficiency (1.5 pts). Score ≥2 = high risk. More discriminatory than HAS-BLED for VTE-specific bleeding.

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Shared decision-making: The decision to continue or stop anticoagulation at 3–6 months should be made collaboratively with the patient, weighing the annual VTE recurrence risk (~10% for unprovoked), bleeding risk, patient preference, and need for ongoing monitoring. Residual DVT on ultrasound and persistently elevated D-dimer at the end of treatment are associated with higher recurrence risk and may support extended therapy.

Thrombophilia Testing — When and For Whom

Routine thrombophilia testing is not recommended for all PE patients. Testing is considered in specific circumstances:

Young patients (<50 years) with unprovoked PE, especially if the result would change management (e.g., decision regarding extended anticoagulation).
Recurrent VTE in unusual sites (cerebral, splanchnic, portal).
Strong family history of VTE (multiple first-degree relatives).
Testing should be performed ≥2 weeks after completing acute anticoagulation (ideally at 4–6 weeks off therapy) to avoid false negatives.
Do NOT test during acute VTE or while on anticoagulation (LMWH and DOACs affect antithrombin levels, lupus anticoagulant, and protein C/S assays).

Chronic Thromboembolic Disease

CTEPH Screening Post-PE

Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious long-term complication of acute PE, affecting an estimated 2–4% of PE survivors. It results from incomplete resolution of pulmonary thromboemboli, leading to organised fibrotic obstruction of the pulmonary vasculature and progressive pulmonary hypertension. CTEPH is the only potentially curable form of pulmonary hypertension through pulmonary endarterectomy (PEA).

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Screening recommendation: All patients who have had a PE should be evaluated for persistent dyspnoea or exercise limitation at 3–6 months post-PE. If symptoms persist disproportionate to residual cardiopulmonary disease, proceed to echocardiography. This is endorsed by the ESC and the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ).

Screening Algorithm

1

Clinical Assessment at 3–6 Months

Assess for persistent dyspnoea (mMRC scale), exercise intolerance, and functional limitation. Normalise for expected recovery trajectory.

2

Transthoracic Echocardiography

Estimate RVSP. Signs of RV pressure overload: RV dilation, tricuspid regurgitation velocity >2.8 m/s, septal flattening. If suggestive of PH → refer to PH specialist centre.

3

Right Heart Catheterisation

Confirms pulmonary hypertension: mPAP ≥20 mmHg at rest. Differentiates pre-capillary (PAWP ≤15) from post-capillary PH.

4

V/Q Scan and CT Pulmonary Angiography

V/Q scan is the screening test of choice for CTEPH (sensitivity ~96%). A normal V/Q scan effectively excludes CTPH. CTPA with chronic thrombotic features: webs, bands, vessel narrowing, organised thrombus.

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Pulmonary Angiography & Surgical Assessment

Conventional or digital subtraction pulmonary angiography defines the distribution and operability of chronic thrombotic lesions. Multidisciplinary assessment for PEA surgery at a CTEPH expert centre.

CTEPH Treatment Options

Pulmonary endarterectomy (PEA): Treatment of choice for operable CTEPH. Median sternotomy, deep hypothermic circulatory arrest. Performed at select centres in Australia (Royal Prince Alfred Hospital, Sydney, is the primary PHSANZ-designated CTEPH centre). Perioperative mortality 2–5% at experienced centres. Can be curative.
Balloon pulmonary angioplasty (BPA): Catheter-based treatment for patients with inoperable CTEPH or residual PH after PEA. Performed in a staged fashion (multiple sessions). Increasingly available in Australian PH centres. Improves haemodynamics and functional capacity in the CHEST-UK and Japanese registries.
Medical therapy: Riociguat (soluble guanylate cyclase stimulator) is PBS-listed (Authority Required) for inoperable CTEPH. WHO functional class improvement demonstrated in the CHEST-1 trial. Other PH-specific therapies (macitentan, sildenafil, epoprostenol) may be used off-label in specialist centres.
Lifelong anticoagulation: All CTEPH patients require indefinite anticoagulation (typically warfarin; DOACs increasingly used but less evidence in CTEPH specifically).

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Riociguat

Adempas® · Soluble guanylate cyclase stimulator

Adult dose 1 mg PO TDS initially, titrate by 0.5 mg TDS every 2 weeks. Maximum 2.5 mg TDS.

Indication Inoperable CTEPH, or persistent/recurrent PH after PEA surgery

Key cautions Contraindicated with PDE-5 inhibitors (sildenafil, tadalafil) — risk of severe hypotension. Contraindicated in pregnancy (teratogenic). Smoking reduces exposure by ~50–60%.

PBS status 🔒 PBS Authority Required (Specialist)

Residual Symptoms Post-PE

Up to 50% of PE survivors report persistent symptoms at 6 months, including exertional dyspnoea, exercise intolerance, and reduced quality of life. This entity is increasingly recognised as "post-PE syndrome" and may occur in the absence of CTEPH.

Pathophysiology: May include residual pulmonary vascular obstruction, deconditioning, cardiac remodelling (RV dysfunction), microvascular disease, and chronic thromboembolic disease without meeting haemodynamic criteria for CTEPH.
Investigations: Echocardiography, 6-minute walk test (6MWT), cardiopulmonary exercise testing (CPET), and pulmonary function tests. CT pulmonary angiography may demonstrate residual thrombus.
Management: Supervised exercise-based cardiac rehabilitation has shown benefit (PEITHO-2, EINSTEIN CHOICE sub-studies). Pulmonary rehabilitation programs available through Australian public hospitals and community services.
Dyspnoea evaluation: Comprehensive assessment should include cardiac (echocardiography, BNP), pulmonary (PFTs, CT chest), deconditioning (CPET), and psychological factors (anxiety, PTSD post-acute PE are common).

Specialist Referral Pathways

Referral Pulmonary hypertension specialist centre PHSANZ-accredited centres for CTEPH assessment and management. Required for right heart catheterisation, BPA, and PEA surgical assessment. Key centres: Royal Prince Alfred (Sydney), Alfred Hospital (Melbourne), Royal Adelaide, Princess Alexandra (Brisbane).

Referral Haematology / Thrombosis service For complex anticoagulation decisions, thrombophilia workup, cancer-associated VTE, and anticoagulation in challenging patient groups (e.g., antiphospholipid syndrome, pregnancy).

Referral Respiratory medicine For post-PE dyspnoea evaluation, pulmonary rehabilitation, CPET, and exclusion of alternative/comorbid respiratory pathology (COPD, ILD).

Referral Cardiology / Heart failure service For RV dysfunction follow-up, cardiac remodelling assessment, and exclusion of other causes of right heart failure.

Special Populations

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Pregnancy

Diagnosis: V/Q scan preferred over CTPA in many Australian centres (lower foetal radiation dose with modern protocols). CTPA with low-dose protocol is an acceptable alternative. D-dimer is unreliable in pregnancy (physiologically elevated).

Treatment: LMWH (enoxaparin 1 mg/kg SC BD, adjusted by anti-Xa levels — target 0.5–1.0 IU/mL 4 hours post-dose) is the anticoagulant of choice. Warfarin is teratogenic in the first trimester (warfarin embryopathy) and should be avoided. DOACs are contraindicated in pregnancy.

Delivery planning: Transition to UFH at 36–37 weeks or earlier if preterm delivery anticipated. Discontinue UFH 4–6 hours before planned induction/CS. Restart LMWH 6–12 hours post-delivery if no significant bleeding.

Thrombolysis: Life-threatening massive PE in pregnancy — thrombolysis is not absolutely contraindicated but carries a significant maternal haemorrhage risk (~15%). Multidisciplinary decision involving obstetrics, haematology, and intensive care.

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Paediatrics

Epidemiology: PE is rare in children (incidence ~0.9 per 100,000). Associated with central venous catheters (~50% of paediatric PE), malignancy, inherited thrombophilia, nephrotic syndrome, and cardiac disease.

Diagnosis: CTPA is first-line. Wells score and PERC not validated in paediatrics. D-dimer has limited utility. Consider clinical context and risk factors.

Treatment: UFH or LMWH (enoxaparin: <2 months 1.5 mg/kg SC BD; ≥2 months 1 mg/kg SC BD — anti-Xa guided dosing). Transition to warfarin for long-term therapy (INR 2.0–3.0). DOACs increasingly studied in paediatric VTE (EINSTEIN-Jr for rivaroxaban — TGA-approved in Australia for paediatric VTE ≥birth weight).

Duration: Minimum 3 months for provoked PE; 6 months for unprovoked. Consider extended therapy with haematology guidance for recurrent events.

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Elderly (≥65 years)

Diagnosis: Age-adjusted D-dimer cutoffs (age × 10 µg/L for patients >50) are essential to reduce false positives. Higher prevalence of PE-related ECG changes mimicking ACS. Pre-existing cardiopulmonary disease confounds interpretation.

Anticoagulation: DOACs preferred over warfarin (fewer drug interactions, no INR monitoring, lower ICH risk). Apixaban has the most favourable safety profile in elderly (ARISTOTLE, AMPLIFY). Dose reduction criteria: apixaban 2.5 mg BD if ≥2 of age ≥80, weight ≤60 kg, Cr ≥133 µmol/L. Rivaroxaban 15 mg if eGFR 15–49.

Bleeding risk: HAS-BLED and VTE-BLEED scores are critical in this population. Falls risk assessment is relevant but isolated falls are generally NOT a contraindication to anticoagulation. Polypharmacy review is essential.

Special considerations: Low-molecular-weight heparin dose reduction may be required in frail elderly with low muscle mass and low body weight. Regular renal function monitoring (at least 3-monthly on LMWH or DOACs).

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Renal Impairment

eGFR ≥30 mL/min: Standard anticoagulation regimens (LMWH, DOACs) are generally appropriate. Monitor anti-Xa levels for LMWH if eGFR 30–50.

eGFR 15–29 mL/min: UFH is preferred over LMWH. If LMWH required, dose-reduce and monitor anti-Xa levels (target 0.5–1.0 IU/mL). Rivaroxaban 15 mg OD may be considered (limited data). Apixaban use with caution.

eGFR <15 mL/min / dialysis: UFH is the agent of choice. DOACs are not recommended. Warfarin may be used (no renal clearance) but requires careful INR monitoring. Thrombolysis dose is unchanged (not renally cleared).

CTPA considerations: IV iodinated contrast: hydrate pre- and post-procedure; use iso-osmolar or low-osmolar contrast. Avoid if eGFR <15. Consider V/Q scan as alternative if eGFR <30. N-acetylcysteine has no proven benefit for contrast nephropathy prevention.

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Hepatic Impairment

Mild hepatic impairment (Child-Pugh A): Standard anticoagulation generally appropriate. Monitor LFTs. DOACs may be used with caution (apixaban and rivaroxaban are hepatically metabolised).

Moderate-severe (Child-Pugh B/C): DOACs are NOT recommended (altered metabolism, unpredictable drug levels, coagulopathy). UFH preferred for acute treatment. Warfarin with careful INR monitoring for long-term therapy. LMWH may have reduced efficacy due to low antithrombin levels (consider antithrombin supplementation if available).

Portal vein thrombosis: Associated with cirrhosis. Anticoagulation recommended to prevent extension and improve portal vein recanalisation. LMWH or DOACs (in Child-Pugh A/B) are appropriate. Specialist hepatology/haematology input essential.

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Immunocompromised

Cancer-associated PE: LMWH (dalteparin per CLOT trial) or DOACs (apixaban per CARAVAGGIO, edoxaban per Hokusai VTE Cancer). DOACs are contraindicated in GI malignancy due to increased GI bleeding (6–8% absolute increase in major GI bleeding). LMWH preferred for oesophageal, gastric, and colorectal cancer.

HIV: Increased VTE risk (4–10× general population). Check for antiphospholipid antibodies. Drug interactions with antiretrovirals: protease inhibitors increase DOAC levels (avoid with rivaroxaban); rilpivirine, efavirenz may reduce DOAC levels. Use LMWH → warfarin if uncertain.

Transplant recipients: Drug interactions with calcineurin inhibitors (cyclosporine, tacrolimus) and DOACs (increased levels). Haematology input recommended for anticoagulation selection.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health — Pulmonary Embolism

Aboriginal and Torres Strait Islander Australians experience a higher burden of venous thromboembolism than the non-Indigenous population, with contributing factors including higher prevalence of cardiovascular comorbidities, rheumatic heart disease, obesity, diabetes, and chronic kidney disease. Delays in diagnosis and challenges in accessing specialist care contribute to poorer outcomes. The following considerations apply to PE management in this population.

Higher VTE Incidence

Age-standardised VTE incidence is approximately 1.5–2 times higher in Aboriginal and Torres Strait Islander Australians compared with the non-Indigenous population, based on AIHW and Northern Territory data. Contributing factors include higher prevalence of hospitalisation, surgery, prolonged immobility, and cardiovascular risk factors.

Geographic and Access Barriers

CTPA is available only at major regional hospitals (Alice Springs, Darwin, Cairns, Townsville, Rockhampton). Patients in remote communities (including APY Lands, Arnhem Land, Cape York, Torres Strait Islands) may require aeromedical retrieval (RFDS) for CTPA — causing delays of 6–24 hours. Point-of-care D-dimer and bedside echocardiography (where available) can support clinical decision-making during retrieval.

Co-morbidity Burden

Higher prevalence of rheumatic heart disease (particularly in NT, WA, and Far North Queensland), chronic kidney disease (4–5× higher rates), obesity, and diabetes complicates PE diagnosis and management. These conditions may cause baseline RV dysfunction and elevated biomarkers, confounding submassive PE classification.

Renal Impairment Considerations

Chronic kidney disease is prevalent in Aboriginal and Torres Strait Islander communities (particularly in remote NT and WA). eGFR should be calculated using the CKD-EPI equation. LMWH dose adjustment and monitoring of anti-Xa levels may be required. CTPA contrast protocols should include pre-hydration. V/Q scanning may be preferred if eGFR <30.

VTE Prophylaxis in Hospital

Aboriginal and Torres Strait Islander patients may have delayed presentation to hospital, increasing the window of preventable VTE. Ensure all admitted Aboriginal and Torres Strait Islander patients receive standardised VTE risk assessment per NSQHS Standards. Education on VTE awareness should be culturally appropriate and delivered through Aboriginal health workers and practitioners.

Anticoagulation Access and Monitoring

DOACs are preferred in settings where INR monitoring is impractical (remote communities). Rivaroxaban (once daily after initial phase) and apixaban (twice daily) can be managed without INR monitoring. However, medication adherence and supply chain reliability must be ensured through remote pharmacy services (Remote Area Aboriginal Health Services). PBS co-payment is covered under Closing the Gap PBS co-payment measure for eligible Aboriginal and Torres Strait Islander patients.

Rheumatic Heart Disease and PE

RHD remains endemic in central and northern Australia, particularly in Aboriginal and Torres Strait Islander communities. Patients with RHD (especially those with atrial fibrillation, prosthetic valves, or prior stroke) represent a distinct anticoagulation subgroup — warfarin is often required (DOACs contraindicated with mechanical valves). The RHD register (RHDAustralia) facilitates coordination of anticoagulation care.

Cultural Safety and Communication

Engage Aboriginal health practitioners and liaison officers (AHP/AHLOs) in PE education, consent, and discharge planning. Use plain language and visual aids. Respect cultural obligations (sorry business, kinship obligations) that may affect follow-up. Facilitate return-to-community care through telemedicine respiratory and haematology follow-up where possible.

📚 References

1. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405.
2. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83(3):416-420.
3. Kline JA, Courtney DM, Kabrhel C, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008;6(5):772-780. doi:10.1111/j.1538-7836.2008.02944.x.
4. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA. 2014;311(11):1117-1124. doi:10.1001/jama.2014.2135.
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7. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism (AMPLIFY-EXT). N Engl J Med. 2013;368(8):699-708. doi:10.1056/NEJMoa1207541.
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9. Ghofrani HA, D'Armini AM, Grimminger F, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension (CHEST-1). N Engl J Med. 2013;369(4):319-329. doi:10.1056/NEJMoa1209657.
10. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353(9162):1386-1389. doi:10.1016/S0140-6736(98)07534-5.
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12. RHDAustralia (RHD Australia), a program of Menzies School of Health Research. The 2020 Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: RHDAustralia; 2020.
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14. National Safety and Quality Health Service Standards. 2nd ed. Australian Commission on Safety and Quality in Health Care (ACSQHC), Sydney; 2021.
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