Causes, Diagnosis and Management of Pulmonary Embolism

Causes, Diagnosis and Management of Pulmonary Embolism 15 marks High-Yield Points Definition and Epidemiology

Definition: obstruction of the pulmonary arterial tree, usually by thrombus embolised from the deep veins of the leg or pelvis; part of the spectrum of venous thromboembolism (VTE) together with DVT.

Ageing is the dominant risk factor: both the incidence of VTE and the haemorrhagic risk of its treatment rise with age. Thirty-day mortality after VTE roughly trebles in those aged ≥65 compared with the young (11% vs 4%), and at one year it is 31% vs 14%.

Venous stasis: immobility, hospitalisation, stroke with hemiplegia, heart failure, long travel, obesity, varicose veins.

Endothelial injury: surgery (especially hip and knee arthroplasty and hip fracture), trauma, fracture of a lower limb, central venous catheters, previous DVT.

Hypercoagulability: active malignancy (the single most important acquired factor in the elderly), inflammatory illness, sepsis, nephrotic syndrome, oestrogen therapy, antiphospholipid syndrome, and inherited thrombophilias (factor V Leiden — the commonest; prothrombin 20210A; deficiencies of antithrombin, protein C and protein S). Ageing itself brings raised fibrinogen, altered platelet function and frailty, all independently associated with VTE.

Testing for thrombophilia is rarely useful in the elderly — levels of antithrombin, protein C and S fall during acute thrombosis and during anticoagulation, so the patient must be off treatment and thrombosis-free. First presentation in old age is usually provoked or cancer-associated rather than inherited.

Classic: sudden pleuritic chest pain, dyspnoea, tachypnoea, tachycardia, haemoptysis, syncope; massive PE presents with hypotension, cardiogenic shock or cardiac arrest.

In the elderly the presentation is blunted and non-specific — isolated dyspnoea, unexplained tachypnoea, new atrial fibrillation, syncope or a fall, delirium, or simply unexplained deterioration. Asymptomatic DVT is present on admission in a high proportion of older medical inpatients. PE shares fever, cough, chest pain and dyspnoea with pneumonia; clear lung fields on chest X-ray with marked hypoxaemia should raise suspicion.

Step 1 — assess pre-test clinical probability using the Wells score or the revised Geneva score. The revised Geneva score is objective (no subjective "PE most likely diagnosis" item), which makes it preferable in older patients: Revised Geneva score (Pathy's Table 37.2) Points Age >65 years 1 Previous DVT or PE 3 Surgery under general anaesthesia or lower-limb fracture within 1 month 2 Active cancer (or cured <1 year) 2 Unilateral lower-limb pain 3 Haemoptysis 2 Pain on deep venous palpation and unilateral oedema 4 Heart rate 75–94 / ≥95 beats per minute 3 / 5 Clinical probability: Low 0–3 | Intermediate 4–10 | High >10

Step 2 — D-dimer, but only if probability is low or intermediate. D-dimer rises physiologically with age, so the conventional 500 µg/L cut-off has poor specificity in the elderly. Use the age-adjusted cut-off = age × 10 µg/L for patients over 50 (validated in the ADJUST-PE study, JAMA 2014) — this substantially increases the proportion of older patients in whom PE can be excluded without imaging, at no cost in safety.

Step 3 — imaging. CT pulmonary angiography (CTPA) is the investigation of choice. In renal impairment consider V/Q or V/Q-SPECT scanning, or a compression ultrasound of the legs first (a positive proximal DVT in a breathless patient justifies treatment without CTPA). Pathy's notes a randomised trial showing that sodium bicarbonate hydration before CTPA in chronic kidney disease was no better than no hydration.

Diagnostic algorithm (Pathy's Figure 37.2): haemodynamically stable patient → assess probability → if low/intermediate, D-dimer (age-adjusted): negative excludes PE, positive proceeds to CTPA; if high probability, go directly to CTPA. In the unstable patient, bedside echocardiography showing right ventricular dilatation/dysfunction justifies immediate treatment.

Supporting tests: ECG (sinus tachycardia commonest; right axis deviation, right bundle branch block, T inversion V1–V4, the classic but uncommon S1Q3T3); chest X-ray usually normal or shows atelectasis, a raised hemidiaphragm or a pleural effusion; arterial blood gas shows hypoxaemia with hypocapnia; troponin and NT-proBNP for risk stratification.

PESI and simplified PESI (sPESI) are validated in the elderly and identify patients at low risk of short-term death who may be managed as outpatients. Age is itself a PESI variable, so few older patients score "low risk". The strongest predictors of long-term mortality are systolic BP <100 mmHg, active cancer and age; others are low physical activity, polypharmacy, diabetes, anaemia, hs-CRP >40 mg/L, troponin >14 pg/mL and D-dimer >3000 ng/mL at presentation.

Causes of death in the first three months after VTE in the elderly: cancer 38%, PE 26%, infection 13%, bleeding 6% — a striking set of figures worth quoting.

Immediate: oxygen, analgesia, cautious fluids in right ventricular failure (over-filling worsens it), vasopressors (noradrenaline) if hypotensive, and start anticoagulation during the diagnostic work-up in any patient with intermediate or high clinical probability and no contraindication.

Anticoagulation — DOACs are first choice in the absence of cancer or severe renal impairment, mainly because of their lower intracranial bleeding risk. In patients aged ≥75, DOACs carry a relative risk of major bleeding of 0.49 compared with vitamin K antagonists. Regimens (Pathy's Table 37.3): Drug Lead-in heparin Initial and long-term (3–6 months) Extended phase Dabigatran Yes, ≥5 days 150 mg twice daily No change Rivaroxaban No 15 mg twice daily × 21 days, then 20 mg Consider 10 mg once daily once daily Apixaban No 10 mg twice daily × 7 days, then 5 mg Consider 2.5 mg twice daily twice daily Edoxaban Yes, ≥5 days 60 mg once daily (30 mg if CrCl 30–50 No change mL/min, weight ≤60 kg, or on strong P-gp inhibitors)

Reperfusion therapy: systemic thrombolysis for high-risk (haemodynamically unstable) PE where bleeding risk is acceptable. Catheter-directed thrombolysis, mechanical thrombectomy or surgical embolectomy for those with contraindications to lysis or failed lysis. An IVC filter is reserved for absolute contraindications to anticoagulation or recurrent PE despite adequate treatment.

Duration: minimum 3 months for all. A provoked PE with a major transient risk factor (surgery, fracture) stops at 3 months. Unprovoked PE or a persistent risk factor (cancer, thrombophilia) warrants extended/indefinite anticoagulation with periodic review of bleeding risk. Cancer-associated VTE: LMWH or an anti-Xa DOAC, continued while cancer is active.

Bleeding risk in the elderly: patients aged ≥65 have a near two-fold higher risk of major and clinically relevant non-major bleeding, and age ≥75 at least doubles the risk of intracranial haemorrhage. Independent predictors include low physical activity and polypharmacy (>4 drugs). Pathy's states that whether falls risk increases major bleeding remains controversial — falls alone are not a reason to withhold anticoagulation. Existing recurrence scores are unhelpful in the old: HERDOO2 automatically classes anyone ≥65 as high risk, DASH is not validated in the elderly, and the Vienna model lacks discriminative power. Therefore clinical judgement plus patient preference must guide the decision.

Prevention: risk-assess every hospitalised older patient; use LMWH thromboprophylaxis unless contraindicated, mechanical prophylaxis (intermittent pneumatic compression) where bleeding risk is high, early mobilisation and adequate hydration.