Medicine chapters
Pulmonary embolism (including the role of DOACs)
Pulmonary embolism is a clot, usually from the deep leg veins, that blocks the pulmonary arteries; this chapter covers risk factors, the Wells and D-dimer pathway, imaging, thrombolysis and anticoagulation with DOACs.
- Most emboli arise from proximal leg and pelvic DVT; risk follows Virchow's triad (stasis, vessel injury, hypercoagulability): surgery, immobility, cancer, pregnancy, oestrogens, thrombophilia.
- Diagnose with the two-level Wells score: PE unlikely (≤4) → D-dimer (negative excludes); PE likely (>4) or raised D-dimer → CTPA (V/Q if pregnant, renal impairment or contrast allergy); shock → bedside echo and thrombolysis.
- DOACs (apixaban, rivaroxaban, edoxaban = anti-Xa; dabigatran = anti-thrombin) are first-line for most PE, for at least 3 months; avoid them in pregnancy, breastfeeding, mechanical valves, severe renal failure and antiphospholipid syndrome.
On this page
Overview
Pulmonary embolism (PE) is blockage of the pulmonary arteries, usually by thrombus that has travelled from a deep vein thrombosis (DVT). DVT and PE together are called venous thromboembolism (VTE).
PE is a major preventable cause of death in hospital and in pregnancy. Its features are non-specific, so a structured diagnostic pathway is essential.
The TOS asks for aetiology, diagnosis and the role of DOACs.
Aetiology
Virchow's triad
- Stasis of blood: immobility, surgery, long journeys, plaster casts, heart failure.
- Vessel wall injury: trauma, surgery, central lines.
- Hypercoagulability: cancer, pregnancy, oestrogens, thrombophilia.
Venous clots form mainly through stasis and hypercoagulability; most begin in the valve pockets of the calf (soleal) veins and become dangerous when they extend into the popliteal, femoral and iliac veins.
Risk factors
| Transient (provoking) | Persistent |
|---|---|
| Major surgery, especially hip, knee, pelvic and cancer surgery | Active cancer (pancreas, lung, stomach, brain, ovary) |
| Trauma, fractures | Previous VTE |
| Immobility (bed rest more than 3 days), stroke with paralysis | Increasing age, obesity |
| Pregnancy and the puerperium | Inherited thrombophilia: factor V Leiden, prothrombin gene mutation, antithrombin, protein C and protein S deficiency |
| Combined pill and HRT | Antiphospholipid syndrome |
| Long-haul travel (more than 4 hours) | Nephrotic syndrome, inflammatory bowel disease, Behçet disease |
| Central venous catheter, heparin-induced thrombocytopenia | Myeloproliferative neoplasms, paroxysmal nocturnal haemoglobinuria |
Up to half of VTE episodes have no clear cause (unprovoked). Non-thrombotic emboli include fat (long-bone fractures), air, amniotic fluid and tumour.
Pathophysiology in brief
- Clot blocks pulmonary arteries → dead space ventilation and V/Q mismatch → hypoxaemia; the patient hyperventilates → low PaCO2.
- A large clot raises pulmonary vascular resistance → acute right ventricular strain, dilatation and failure → low cardiac output, hypotension, shock and PEA arrest.
- Small peripheral emboli cause pulmonary infarction (pleuritic pain, haemoptysis, effusion).
Clinical features
| Presentation | Features |
|---|---|
| Small or medium PE (commonest) | Pleuritic chest pain, breathlessness, haemoptysis; tachypnoea, tachycardia, pleural rub, low-grade fever |
| Isolated breathlessness | Sudden unexplained dyspnoea, often exertional |
| Massive PE | Collapse or syncope, systolic BP <90 mmHg, shock, central chest pain, cyanosis, raised JVP, RV heave, gallop, loud or widely split P2; cardiac arrest with PEA |
| Chronic recurrent emboli | Progressive breathlessness and pulmonary hypertension (CTEPH) |
Look for a swollen, tender leg (DVT); it is clinically obvious in only a minority.
Initial tests (supportive, not diagnostic)
| Test | Typical findings |
|---|---|
| ECG | Sinus tachycardia (commonest); RV strain (T inversion V1–V4 and inferior leads), right bundle branch block, right axis deviation; S1Q3T3 (deep S in I, Q and inverted T in III) is classic but uncommon; new AF |
| ABG | Hypoxaemia with hypocapnia (type 1 failure), respiratory alkalosis |
| Chest X-ray | Often normal; may show atelectasis, small effusion, raised hemidiaphragm; rare Westermark sign (oligaemic lucent zone) and Hampton hump (wedge-shaped peripheral infarct). Mainly used to exclude other causes |
| Troponin, BNP | Raised with RV strain; worse prognosis |
A breathless, hypoxic patient with a clear chest X-ray should make you think of PE.
Diagnosis: the Wells and D-dimer pathway (haemodynamically stable)
Two-level Wells score for PE
| Feature | Points |
|---|---|
| Clinical signs of DVT (leg swelling and deep vein tenderness) | 3 |
| PE more likely than any alternative diagnosis | 3 |
| Heart rate >100/min | 1.5 |
| Immobilisation more than 3 days or surgery in the last 4 weeks | 1.5 |
| Previous DVT or PE | 1.5 |
| Haemoptysis | 1 |
| Active cancer (treated within 6 months or palliative) | 1 |
PE likely: more than 4 points. PE unlikely: 4 or fewer.
Woman 10 days after hip surgery: swollen tender calf, HR 112/min, PE is the most likely diagnosis
DVT signs 3 + PE most likely 3 + HR >100 1.5 + surgery in last 4 weeks 1.5 = 9
Score 9 (>4) → PE likely → go straight to CTPA (start anticoagulation while waiting); no D-dimer needed
The pathway
- PE unlikely (≤4) → D-dimer.
- Negative D-dimer → PE excluded; look for another diagnosis.
- Raised → CTPA.
- PE likely (>4) → CTPA directly. Give a first dose of anticoagulant if imaging will be delayed (more than about 1 hour for suspected PE).
- CTPA negative but suspicion still high → leg ultrasound or V/Q scan.
About D-dimer
- A fibrin breakdown product; high sensitivity and high negative predictive value, poor specificity.
- Raised after surgery, trauma, infection, cancer, pregnancy, in old age and in DIC.
- Use it only when probability is low. Never use it alone to diagnose PE.
Do not send a D-dimer when the Wells score says PE is likely, in late pregnancy, or after recent surgery; a positive result tells you nothing and a negative one may not be trusted. Go to imaging.
Imaging
| Test | Points |
|---|---|
| CT pulmonary angiography (CTPA) | First-line; shows filling defects, RV size and alternative diagnoses. Needs contrast and radiation |
| V/Q (isotope) scan | Shows perfusion defects with normal ventilation (mismatch). A normal scan excludes PE. Preferred in renal impairment, contrast allergy and pregnancy (lower breast radiation); less useful with abnormal chest X-ray |
| Compression ultrasound of legs | Positive proximal DVT in a patient with PE symptoms allows treatment without lung imaging |
| Echocardiography | Bedside in shocked patients: dilated, hypokinetic RV, raised pulmonary pressure, sometimes clot in transit |
Suspected massive PE (shock or hypotension)
- Systolic BP <90 mmHg or a fall of more than 40 mmHg for over 15 minutes, not due to other causes.
- CTPA if immediately available; if not, or the patient is too unstable, bedside echo showing RV dysfunction is enough to justify thrombolysis.
Management
Immediate measures
- Oxygen to target saturations, IV access, cautious fluids (too much fluid worsens RV failure), analgesia.
- Risk stratify stable PE using the PESI or simplified PESI score, troponin, BNP and RV size. Low-risk patients may be treated as outpatients.
Massive (high-risk) PE
- Systemic thrombolysis with alteplase (a relatively fibrin-specific tissue plasminogen activator) if no contraindication; can be given during cardiac arrest from PE.
- About 2% risk of intracranial bleeding; contraindications are the same as in MI (previous haemorrhagic stroke, recent major surgery, active bleeding).
- If thrombolysis is contraindicated or fails: surgical embolectomy or catheter-directed therapy.
- Then start unfractionated heparin (easier to stop and reverse).
Thrombolysis is reserved for PE with hypotension (systolic <90 mmHg). In stable PE with RV strain (intermediate risk), anticoagulate and monitor; thrombolysis is only a rescue option.
Anticoagulation (the mainstay)
Anticoagulants stop clot growth and new clots; the body's own fibrinolysis dissolves the existing clot. They do not dissolve clot directly.
Three models:
| Approach | Details |
|---|---|
| LMWH then warfarin | LMWH (e.g. enoxaparin) for at least 5 days and until INR ≥2 for 24 hours; warfarin target INR 2.5 (2–3) |
| LMWH then dabigatran or edoxaban | 5 days of parenteral heparin, then switch on day 6 (no overlap) |
| Apixaban or rivaroxaban alone | Start from day 1 without heparin, at a higher loading dose (apixaban for 7 days, rivaroxaban for 21 days), then a maintenance dose |
Role of DOACs
Direct oral anticoagulants (DOACs) are now the first-line treatment for most patients with PE or DVT because they are as effective as warfarin with a lower risk of intracranial bleeding.
The drugs
| Drug | Target | Kidney clearance | Lead-in heparin | Specific reversal |
|---|---|---|---|---|
| Apixaban | Factor Xa | About 25% | No | Andexanet alfa |
| Rivaroxaban | Factor Xa | About 33% (take with food) | No | Andexanet alfa |
| Edoxaban | Factor Xa | About 50% | Yes, 5 days | Andexanet alfa |
| Dabigatran | Thrombin (IIa) | About 80% | Yes, 5 days | Idarucizumab |
| Warfarin (for comparison) | Vitamin K-dependent II, VII, IX, X | No | Yes, until INR ≥2 | Vitamin K, prothrombin complex concentrate |
Dabigatran depends most on the kidneys (about 80% renal clearance), so it is the DOAC most affected by renal impairment and is avoided when creatinine clearance is below 30 mL/min.
Advantages
- Fixed doses, no routine INR monitoring.
- Rapid onset (peak in about 2 hours) and short half-life (about 12 hours).
- Few food interactions and fewer drug interactions than warfarin.
- Similar or lower major bleeding; less intracranial haemorrhage, but some (especially dabigatran and rivaroxaban) cause more GI bleeding.
When to avoid DOACs (use LMWH or warfarin)
- Pregnancy and breastfeeding (DOACs cross the placenta) → LMWH.
- Mechanical heart valves and moderate to severe mitral stenosis → warfarin.
- Antiphospholipid syndrome, especially triple-positive → warfarin (DOACs less effective).
- Severe renal impairment: factor Xa inhibitors not below CrCl 15 mL/min; dabigatran not below CrCl 30 mL/min.
- Severe liver disease, active bleeding.
- Interacting drugs: strong inducers (rifampicin, carbamazepine, phenytoin) lower DOAC levels; HIV protease inhibitors and azoles raise them.
- Cancer-associated VTE: LMWH or a DOAC (apixaban, rivaroxaban, edoxaban) are both acceptable; prefer LMWH with GI or genitourinary cancers because DOACs raise bleeding there.
Bleeding on a DOAC
- Stop the drug; supportive care, transfusion, local control (e.g. endoscopy).
- Life-threatening bleeding: idarucizumab for dabigatran; andexanet alfa for anti-Xa drugs, or prothrombin complex concentrate if unavailable.
- Before planned major surgery, DOACs are usually stopped about 48 hours ahead (longer for dabigatran with poor kidney function).
"X-abans block Xa": apixaban, rivaroxaban, edoxaban; dabigatran blocks thrombin (gatran → "gate" to thrombin).
Do not give a DOAC to a pregnant woman or a patient with a mechanical valve; in pregnancy use LMWH, which does not cross the placenta.
Duration of treatment
| Situation | Duration |
|---|---|
| PE or proximal DVT with a transient provoking factor (e.g. surgery) | 3 months |
| Unprovoked PE | At least 3 months, then usually long-term if bleeding risk is low |
| Active cancer | At least 6 months and while cancer is active |
| Isolated calf DVT | Often 6 weeks to 3 months |
If anticoagulation is impossible
A retrievable inferior vena cava (IVC) filter (e.g. active major bleeding), removed once anticoagulation is safe.
Complications
- Death (mostly in the first hours), cardiogenic shock, arrhythmia.
- Recurrent VTE.
- Chronic thromboembolic pulmonary hypertension (CTEPH) after a small proportion of PEs; treated with pulmonary endarterectomy.
- Post-thrombotic syndrome of the leg after DVT.
- Bleeding from treatment; heparin-induced thrombocytopenia (platelet fall and new clot 5–10 days after heparin; stop heparin, use argatroban or a non-heparin agent).
Prevention
- Assess every admitted patient for VTE and bleeding risk.
- LMWH prophylaxis, early mobilisation, compression stockings or intermittent pneumatic compression.
- Extended prophylaxis after hip and knee replacement (LMWH, or DOACs such as rivaroxaban, apixaban, dabigatran in low dose).
Expect: Virchow's triad and risk factors, deep leg veins as the source, sinus tachycardia as the commonest ECG finding and S1Q3T3, hypoxaemia with hypocapnia, the two-level Wells score (cut-off 4) and when to use D-dimer, CTPA as first imaging, V/Q scan in pregnancy or renal failure, echo and thrombolysis (alteplase) for massive PE with hypotension, DOAC mechanisms (anti-Xa versus anti-thrombin), heparin lead-in for dabigatran and edoxaban but not apixaban or rivaroxaban, reversal agents (idarucizumab, andexanet), situations where DOACs are avoided (pregnancy, mechanical valves, antiphospholipid syndrome, severe renal impairment), LMWH in pregnancy, warfarin INR target 2–3, 3 months for provoked PE, and IVC filters when anticoagulation is contraindicated.
Quick revision
- Source: proximal leg and pelvic DVT; Virchow's triad.
- Features: pleuritic pain, dyspnoea, haemoptysis, tachycardia; massive PE = SBP <90.
- ECG: sinus tachycardia commonest; S1Q3T3 uncommon.
- Wells ≤4 → D-dimer (negative excludes); >4 → CTPA.
- V/Q in pregnancy, renal failure, contrast allergy; echo if shocked.
- Massive PE: alteplase; if contraindicated, embolectomy.
- DOACs: anti-Xa (apixaban, rivaroxaban, edoxaban), anti-IIa (dabigatran).
- Avoid DOACs: pregnancy, breastfeeding, mechanical valve, APS, severe CKD.
- Provoked PE: 3 months; unprovoked: consider long-term.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
Can a negative D-dimer rule out PE?
Yes, but only when the Wells score shows PE is unlikely; in high-probability patients imaging is needed whatever the D-dimer.
Which DOACs need heparin first?
Dabigatran and edoxaban are started after at least 5 days of parenteral heparin; apixaban and rivaroxaban can be used alone from day 1 at a higher initial dose.
Why are DOACs avoided in pregnancy?
They cross the placenta and their fetal safety is not established; low-molecular-weight heparin, which does not cross, is the treatment of choice.
When is thrombolysis used in PE?
For massive (high-risk) PE with systolic blood pressure below 90 mmHg or cardiac arrest, provided there is no absolute contraindication.
What reverses dabigatran?
Idarucizumab, a monoclonal antibody fragment that binds dabigatran; the factor Xa inhibitors are reversed with andexanet alfa or, if unavailable, prothrombin complex concentrate.