Pulmonary embolism

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

The NICE diagnostic pathway deliberately separates clinical probability from D-dimer and imaging. A positive D-dimer is not a PE diagnosis; a negative test is useful only in an appropriate low-probability pathway.

Severity is defined by haemodynamics and RV impact, not clot size alone. Shock requires immediate reperfusion discussion; stable patients may be eligible for outpatient treatment only after a validated risk tool and practical safety assessment.

Anticoagulant selection and duration are individual. The plan must state the loading phase, maintenance dose, minimum duration, review date, bleeding advice and who will decide extended prevention.

Key points

PE ranges from incidental segmental clot to obstructive shock; haemodynamic instability overrides routine outpatient diagnostic sequencing.
If overall clinical suspicion is low and another diagnosis is feasible, consider the PERC rule to decide whether further PE testing is needed.
Use the 2-level PE Wells score: more than 4 means PE likely and prompts immediate CTPA; 4 or less means PE unlikely and prompts D-dimer first.
If CTPA or D-dimer cannot be obtained within the NICE timeframe, give interim therapeutic anticoagulation unless contraindicated after baseline bloods; do not wait for lab results to start it.
For confirmed stable PE, NICE first-line options are apixaban or rivaroxaban when suitable; renal impairment, active cancer, antiphospholipid syndrome, extreme body weight, pregnancy and interactions may change the choice.
For PE with haemodynamic instability, use continuous UFH and consider systemic thrombolysis; do not routinely thrombolyse a haemodynamically stable PE even when RV dysfunction is present.
Treat confirmed PE for at least 3 months; at 3 months reassess provoking factor, recurrence risk, bleeding risk and preference before stopping or extending.
In PE-related cardiac arrest, RCUK 2025 supports fibrinolysis, surgical embolectomy or percutaneous thrombectomy for known PE and considering 60–90 minutes of CPR after thrombolysis in selected suspected cases.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Embolised deep-vein thrombosis

Most pulmonary emboli arise when thrombus from a deep leg or pelvic vein detaches and travels through the right heart into the pulmonary arterial circulation.

Transient provoking factors

Surgery, trauma, hospitalisation, immobility, pregnancy, the postpartum period and oestrogen exposure promote venous stasis, endothelial injury or increased coagulability, making thrombus formation more likely.

Persistent prothrombotic states

Active cancer, antiphospholipid syndrome and some chronic inflammatory disorders can sustain a prothrombotic tendency. Previous venous thromboembolism is an important marker of increased recurrence risk.

Apparently unprovoked disease

Some events have no identifiable transient trigger. This phenotype may reflect an unrecognised or enduring predisposition and generally carries a higher recurrence risk, which matters when treatment duration is reviewed.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Venous thrombus formation
Venous stasis, vessel-wall injury and hypercoagulability allow fibrin-rich thrombus to develop, most often within the deep veins of the lower limb or pelvis.
2
Embolisation
Part of the thrombus dislodges, passes through the vena cava and right-sided chambers, then lodges within pulmonary arteries according to its size and the vessel calibre.
3
Acute right-ventricular afterload
Mechanical obstruction and vasoconstrictor responses abruptly increase pulmonary vascular resistance. The right ventricle dilates, wall stress rises and septal displacement can impair left-ventricular filling.
4
Gas-exchange and circulatory failure
Ventilation-perfusion mismatch may cause hypoxaemia, while reduced left-sided preload lowers cardiac output. Extensive obstruction may therefore progress to right-ventricular myocardial injury, obstructive shock or cardiac arrest.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Typical PE

Acute dyspnoea, pleuritic chest pain, tachycardia, tachypnoea, hypoxaemia, haemoptysis or unilateral DVT signs; none is individually diagnostic.

High-risk PERed flag

Cardiac arrest, persistent hypotension, shock, altered mentation, cool peripheries or rising lactate indicates obstructive RV failure and needs immediate reperfusion assessment.

Intermediate-risk feature

A stable BP with RV dysfunction and positive cardiac biomarkers increases monitoring need but does not by itself justify routine systemic thrombolysis.

Subtle presentation

Syncope, unexplained tachycardia, new AF, mild hypoxaemia or decompensated HF may be the only clues, particularly in older or frail patients.

Chronic thromboembolic disease

Persistent breathlessness, exercise limitation or pulmonary hypertension after treated PE warrants specialist assessment for post-PE syndrome or CTEPH.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Clinical probability: PERC when suspicion is low, then 2-level PE WellsFirst step
Why
Select who needs no test, D-dimer or immediate imaging.
Interpretation and limitations
Wells >4: PE likely; ≤4: PE unlikely. Do not use PERC in a patient with substantial suspicion or haemodynamic instability.
02
D-dimer
Why
Exclude PE in the PE-unlikely pathway.
Interpretation and limitations
A negative age-adjusted threshold where locally validated can exclude PE; a positive result requires imaging and is non-specific.
03
CT pulmonary angiography
Why
Confirm/exclude PE and define central clot/RV features.
Interpretation and limitations
Offer immediately when Wells >4; if contrast allergy or severe renal impairment, use the NICE alternative imaging route such as V/Q scanning.
04
12-lead ECG, troponin/BNP and transthoracic echo
Why
Assess RV strain, alternative cardiac disease and risk in confirmed/suspected severe PE.
Interpretation and limitations
RV strain supports severity but does not confirm PE alone; in unstable patients echo can support urgent reperfusion when CT is unsafe.
05
FBC, renal/liver function, PT and APTT before anticoagulation
Why
Choose and monitor anticoagulation and establish bleeding baseline.
Interpretation and limitations
Take bloods but do not delay interim anticoagulation while awaiting results; review dose/agent when results return.
06
Leg ultrasound
Why
Detect proximal DVT when PE imaging is contraindicated/indeterminate or DVT signs coexist.
Interpretation and limitations
A proven proximal DVT can establish VTE treatment need, but a negative leg scan does not exclude PE.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Acute coronary syndrome

Pressure-like chest pain with regional ischaemic ECG change or a culprit coronary lesion favours ACS; pleuritic pain, hypoxaemia and venous thrombosis clues favour pulmonary embolism. Troponin elevation can occur in either.

Pneumonia

Fever, purulent sputum, focal crackles and new air-space shadowing support infection, although pneumonia and embolism can coexist and either may raise inflammatory markers.

Pneumothorax

Sudden unilateral pleuritic pain with reduced breath sounds and a visible pleural line suggests pneumothorax; tension physiology requires immediate treatment rather than routine embolism imaging.

Pericarditis or tamponade

Positional pain, a pericardial rub or widespread ECG change suggests pericarditis, while effusion with chamber collapse explains hypotension and raised venous pressure in tamponade.

Acute heart failure

Pulmonary oedema, widespread crackles and left-sided structural disease favour acute heart failure; isolated right-ventricular strain is compatible with embolism but is not diagnostic by itself.

Additional chapter-specific clues

Alternative emergency

ACS, aortic dissection, pneumothorax, pneumonia, pericarditis/tamponade and acute HF must remain in parallel differential diagnosis.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First-lineStable suspected PEFirst stepFirst linePE suspected without haemodynamic instability

1If clinical suspicion is low and another diagnosis is feasible, consider PERC; otherwise calculate the 2-level PE Wells score.
2If Wells >4, arrange immediate CTPA; if imaging is delayed, give interim therapeutic anticoagulation after baseline bloods unless contraindicated.
3If Wells ≤4, obtain D-dimer; if the result is delayed beyond the NICE timeframe, give interim anticoagulation, and image if positive.
4AlternativeIf PE is excluded, stop interim anticoagulation and pursue an alternative diagnosis; give clear safety-net advice.

02Second-lineConfirmed stable PESecond lineImaging-confirmed PE without shock

1Assess bleeding, renal/liver function, cancer, pregnancy potential, antiphospholipid syndrome, weight, interactions and suitability for outpatient care.
2First lineOffer apixaban or rivaroxaban when suitable; use LMWH followed by dabigatran/edoxaban, or LMWH plus VKA, when the first-line DOACs are unsuitable according to NICE.
3Treat for at least 3 months and provide an anticoagulant alert, bleeding/missed-dose advice and written review date.
4Use a validated tool plus clinical/social assessment for outpatient treatment, ensuring rapid access if symptoms worsen.

03Third-lineHaemodynamically unstable PEThird lineShock or persistent hypotension from suspected/confirmed PE

1Start ABCDE, critical-care support and bedside echo; obtain CTPA only if transfer is safe and it will not delay life-saving treatment.
2Give IV UFH: RCUK 2025 advises 80 units/kg IV during the high-risk PE diagnostic process unless bleeding or an absolute contraindication is present, followed by a continuous APTT/anti-Xa-titrated infusion; if alteplase is used, coordinate heparin interruption and resume only when APTT is below twice the upper limit of normal.
3If thrombolysis is contraindicated or fails, discuss surgical embolectomy or catheter-directed/mechanical reperfusion at an experienced centre.
4In cardiac arrest, follow RCUK special-circumstances guidance; after fibrinolysis consider prolonged CPR for 60–90 minutes in selected cases and ECPR where implemented.

04EscalationDuration and recurrence reviewEscalationAt 3 months, recurrent VTE or persistent symptoms

1For a provoked PE with the provoking factor gone and an uncomplicated course, consider stopping after 3 months; active cancer is reviewed at 3–6 months.
2For unprovoked PE, recurrent VTE or persistent risk, consider extended anticoagulation after recurrence-versus-bleeding and preference discussion.
3Investigate suspected antiphospholipid syndrome or cancer only through NICE indications; do not perform indiscriminate thrombophilia testing while anticoagulation decisions are unaffected.
4Refer persistent dyspnoea, RV dysfunction or pulmonary hypertension for post-PE/CTEPH assessment.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

NICE first-line oral anticoagulant for confirmed stable PE when suitable.

Apixaban

10 mg orally twice daily for 7 days, then 5 mg twice daily. If extended prevention is indicated after 6 months of treatment, 2.5 mg twice daily is the licensed recurrence-prevention dose.

Active bleeding, strong dual CYP3A4/P-gp interactions and hepatic coagulopathy. For VTE, use caution when creatinine clearance is 15–29 mL/min and do not use below 15 mL/min or on dialysis; do not apply the AF age/weight/creatinine dose-reduction rule.

NICE first-line oral anticoagulant for confirmed stable PE when suitable.

Rivaroxaban

15 mg orally twice daily with food for 21 days, then 20 mg once daily with food. After day 21 in creatinine clearance 15–49 mL/min, the SmPC allows considering 15 mg once daily if bleeding risk outweighs recurrence risk, but this is pharmacokinetic modelling and was not studied clinically. After at least 6 months, 10 mg once daily (or 20 mg once daily when recurrence risk is high) is licensed for extended prevention.

Active bleeding, hepatic disease with coagulopathy and strong interactions. Use caution when creatinine clearance is 15–29 mL/min and do not use below 15 mL/min; the 15 mg and 20 mg doses must be taken with food.

Parenteral treatment when a DOAC is unsuitable and in selected cancer, pregnancy or bridging pathways.

Enoxaparin

For symptomatic PE, use 1 mg/kg subcutaneously every 12 hours; 1.5 mg/kg once daily is reserved for selected uncomplicated patients at low recurrence risk. At creatinine clearance 15–30 mL/min, a current UK enoxaparin SmPC gives 1 mg/kg subcutaneously once daily; it is not recommended below 15 mL/min outside haemodialysis-circuit use.

Bleeding, thrombocytopenia/HIT, renal accumulation and neuraxial-procedure timing; dose from current weight and creatinine clearance, and never give intramuscularly.

Rapidly adjustable anticoagulation in haemodynamically unstable PE or around thrombolysis/embolectomy.

Unfractionated heparin IV

RCUK 2025 high-risk PE guidance advises heparin 80 units/kg IV during the diagnostic process unless bleeding or an absolute contraindication is present. This differs from the cited UK SmPC regimen of 5,000 units IV (occasionally 10,000 units in severe PE) then 1,000–2,000 units/hour; use one defined regimen, do not stack the boluses, and titrate the continuous infusion to APTT/anti-Xa.

Major bleeding and HIT; check APTT/anti-Xa about 4–6 hours after starting and after rate changes, then at least daily once stable, and monitor platelets. Coordinate interruption/resumption around thrombolysis and never overlap unsafely with a DOAC.

Systemic reperfusion for PE with haemodynamic instability after specialist risk assessment.

Alteplase

For acute massive PE in adults weighing at least 65 kg, the licensed dose is 10 mg IV over 1–2 minutes followed immediately by 90 mg as a constant IV infusion over 2 hours (100 mg total). Below 65 kg, give the same 10 mg bolus then infuse up to a maximum total dose of 1.5 mg/kg over 2 hours. PE arrest uses a separate emergency regimen.

Intracranial and major bleeding, recent surgery/trauma and other contraindications; not routine for stable PE with RV dysfunction alone. After alteplase, initiate or resume heparin only when APTT is below twice the upper limit of normal, then adjust it to APTT 50–70 seconds (1.5–2.5 times the reference value).

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Obstructive shock and cardiac arrest

A large acute rise in pulmonary resistance can overwhelm the right ventricle, sharply reduce left-ventricular preload and cause hypotension, tissue hypoperfusion, pulseless electrical activity or death.

Right-ventricular injury

Pressure overload may cause right-ventricular dilatation, ischaemia and biomarker release. Even with preserved blood pressure, right-ventricular dysfunction indicates reduced reserve and a greater risk of deterioration.

Pulmonary infarction

Peripheral arterial occlusion can produce haemorrhagic lung infarction, pleuritic pain, haemoptysis and a reactive pleural effusion, particularly when collateral bronchial flow is inadequate.

Recurrent or chronic thromboembolic disease

Recurrent emboli or incomplete thrombus resolution may cause persistent exercise limitation or other post-embolism symptoms; a minority develop chronic thromboembolic pulmonary hypertension with progressive right-sided heart failure.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Haemodynamics, oxygenation, respiratory effort, mental state, urine output and lactate in severe PE.
Bleeding, haemoglobin, platelets, renal/liver function and interacting medicines during anticoagulation.
Correct completion of DOAC loading-to-maintenance transition and adherence/missed-dose understanding.
For UFH: APTT or anti-Xa about 4–6 hours after starting and each rate change, then at least daily once stable, plus platelet/HIT surveillance; for VKA: INR through the anticoagulation service.
At 3 months: provoking factor, recurrence risk, bleeding risk, cancer status, preference and explicit stop/extend decision.
Persistent breathlessness, exercise capacity and signs of pulmonary hypertension/CTEPH after the acute event.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

PERC precedes Wells only in low suspicion

PERC is a rule-out aid for a genuinely low-risk patient; it must not reassure in shock or substantial clinical suspicion.

Baseline bloods do not create a treatment delay

Take FBC, renal/liver function and coagulation before interim anticoagulation, but NICE says not to wait for the results.

RV strain is severity, not proof

Echo/ECG/troponin can stratify confirmed PE, but similar RV findings occur in chronic pulmonary hypertension and other disease.

Stable RV dysfunction is not a thrombolysis mandate

Monitor closely and rescue if deterioration occurs; routine systemic lysis adds bleeding without a blanket NICE indication.

DOAC phases are indication-specific

Apixaban VTE treatment does not use the AF dose-reduction rule, and rivaroxaban changes dose after day 21 with food requirements.

Persistent symptoms need a diagnosis

Do not label all post-PE breathlessness as deconditioning; assess recurrence, CTEPH, cardiac/lung disease and post-PE syndrome.

11Common pitfallsFrequent interpretation and management errors.

01
Ordering D-dimer in a PE-likely patient instead of arranging immediate CTPA.
02
Treating a positive D-dimer as confirmation of PE.
03
Delaying interim therapeutic anticoagulation for imaging or laboratory results when NICE timing cannot be met and bleeding risk permits.
04
Using an AF apixaban dose-reduction rule for acute VTE treatment or forgetting rivaroxaban's loading phase/food requirement.
05
Thrombolysing every stable PE with RV strain or failing to consider reperfusion in obstructive shock.