Pulmonary Embolism — Causes, CTPA Diagnosis, Anticoagulation & Thrombolysis Guide — Symptoms, Causes & Treatment | MyMedicPlus

Pulmonary embolism (PE) is a potentially life-threatening condition caused by partial or complete occlusion of one or more pulmonary arteries by a thrombus — a blood clot that typically originates in the deep veins of the lower limbs or pelvis (DVT — deep venous thrombosis) and embolises to the pulmonary circulation. PE and DVT collectively constitute venous thromboembolism (VTE). PE is one of the most common cardiovascular emergencies, occurring in approximately 1-2 per 1000 adults per year in Western countries — with over 60,000 VTE events annually in the UK. It is the third most common cause of acute cardiovascular death after myocardial infarction and stroke, with an estimated 25,000-30,000 preventable deaths from PE annually in the UK. PE is classified by haemodynamic stability: massive PE (high-risk — haemodynamically unstable: systolic blood pressure below 90 mmHg, cardiogenic shock, cardiac arrest) — mortality 30-50% without immediate reperfusion; submassive PE (intermediate-risk — haemodynamically stable but with right ventricular dysfunction on echocardiography or elevated troponin/BNP); and low-risk PE (stable, no RV dysfunction, negative biomarkers). This stratification guides urgency of treatment. Approximately 70-80% of PEs are thought to arise from DVT — thrombus in the proximal deep veins (iliac, femoral, popliteal) carries significantly higher embolisation risk than isolated calf DVT. Importantly, over 50% of patients with acute PE have no clinically apparent DVT. The PESI (Pulmonary Embolism Severity Index) score and simplified PESI (sPESI) risk-stratify PE patients for appropriateness of outpatient management or hospital admission.

Venous thromboembolism occurs when Virchow's triad is present — venous stasis (reduced blood flow), endothelial damage, and a hypercoagulable (prothrombotic) state. Acquired risk factors: major surgery — particularly orthopaedic (total hip and knee replacement — highest surgical VTE risk; hip fracture surgery), abdominal, pelvic (colorectal, gynaecological cancer), and neurosurgical procedures; medical illness — acute myocardial infarction, heart failure, stroke (paralysis causing venous stasis), infection and sepsis (endothelial activation), inflammatory bowel disease, and nephrotic syndrome (urinary loss of antithrombin III); active malignancy — cancer is the most important medical risk factor; Trousseau's syndrome (cancer-associated thrombosis) — mucin-secreting adenocarcinomas of the pancreas, colon, lung, and ovary are most thrombogenic; cancer treatment (chemotherapy, hormone therapy, central venous catheters); pregnancy and the puerperium — VTE risk is 5-fold increased during pregnancy (expanding uterus compresses pelvic veins causing venous stasis; oestrogen-driven hypercoagulability) and 30-fold in the first 6 weeks postpartum; combined oral contraceptive pill — oestrogen-containing OCP increases VTE risk 3-4-fold (highest with 3rd generation progestogens and OCP above 50 mcg oestrogen); HRT; immobility (long-haul air travel — economy class syndrome — risk increases with journeys above 8 hours; hospitalisation; prolonged bed rest); obesity (BMI above 30 — 2-3-fold VTE risk); previous VTE (the strongest predictor of recurrence); and varicose veins (modest risk). Hereditary thrombophilias: factor V Leiden mutation (the most common hereditary thrombophilia — 3-8% of white Europeans; heterozygous confers 5-8-fold VTE risk; homozygous 50-80-fold); prothrombin G20210A mutation (heterozygous — 3-fold risk); protein C deficiency; protein S deficiency; antithrombin III deficiency; antiphospholipid syndrome (APS) — acquired thrombophilia with triple positive antibodies (lupus anticoagulant, anticardiolipin, anti-B2 glycoprotein I) — highest VTE risk.

Symptoms of PE vary from asymptomatic incidental discovery (in cancer screening CT) to sudden cardiorespiratory collapse. Classic presentation: dyspnoea (breathlessness — the most common symptom, present in 80% of PE; often sudden onset, at rest or minimal exertion); pleuritic chest pain (sharp, positional, worsens with inspiration — from pleural involvement, particularly in peripheral or segmental PE with pulmonary infarction); haemoptysis (blood-stained sputum — from pulmonary infarction; present in approximately 30%); tachycardia (the most common sign — heart rate above 100 bpm); and hypoxaemia (low oxygen saturation on pulse oximetry; widened alveolar-arterial oxygen gradient on arterial blood gas — type 1 respiratory failure). Associated DVT signs: unilateral calf or thigh pain, swelling, erythema, and warmth — present in only 30-50% of PE patients with DVT (clinically silent DVT in the remainder). Massive PE signs: haemodynamic instability — hypotension (systolic BP below 90 mmHg or fall above 40 mmHg from baseline); tachycardia (above 110 bpm); signs of right heart failure — raised JVP, right ventricular heave, loud P2 (pulmonary component of the second heart sound), and peripheral cyanosis; syncope or presyncope from low cardiac output; and cardiac arrest (PEA — pulseless electrical activity — a common arrest rhythm in massive PE). Submassive PE (intermediate-risk): haemodynamically stable but ECG shows right heart strain — S1Q3T3 pattern (S wave in lead I, Q wave and inverted T wave in lead III), right bundle branch block, sinus tachycardia, or AF; elevated troponin I or T (RV myocardial injury) and elevated BNP or NT-proBNP (RV wall stress). Examination findings: tachycardia, tachypnoea, elevated JVP, pleural rub (from pulmonary infarction — present in less than 20%), and signs of DVT. Atypical presentations: unexplained syncope or presyncope (PE in up to 10%); worsening breathlessness in a patient with known respiratory disease; unexplained fever (pulmonary infarction).

Clinical probability assessment: the Wells score for PE (maximum 12.5 points) assigns probability as unlikely (score 4 or less) or likely (above 4 points based on: clinical signs of DVT — 3 points; alternative diagnosis less likely than PE — 3 points; heart rate above 100 — 1.5 points; immobility or surgery in past 4 weeks — 1.5 points; previous VTE — 1.5 points; haemoptysis — 1 point; active cancer — 1 point). The PERC rule (8 criteria — all must be met for low-risk rule-out without D-dimer): age below 50, HR below 100, SpO2 above 94%, no unilateral leg swelling, no haemoptysis, no recent surgery, no prior DVT or PE, no oestrogen use. D-dimer assay: a highly sensitive fibrinogen degradation product — a negative D-dimer (below 500 micrograms/L in under-50 patients; age-adjusted threshold = age x 10 micrograms/L in patients above 50, per ADJUST-PE study) has an NPV above 99% for PE in low-to-intermediate probability patients; a positive D-dimer is non-specific (elevated in infection, malignancy, trauma, post-surgery, pregnancy) and requires CTPA. CT pulmonary angiography (CTPA — contrast-enhanced CT): the gold standard imaging investigation — visualises filling defects in pulmonary arteries down to the segmental level; sensitivity 83%, specificity 96%; simultaneously assesses RV/LV diameter ratio (RV dilatation — intermediate-to-high risk PE); identifies alternative diagnoses. V/Q (ventilation-perfusion) scintigraphy: used when CTPA is contraindicated (contrast allergy, renal impairment, pregnancy — lower radiation dose than CTPA); reported as normal (excludes PE), high probability (high likelihood), low/intermediate probability (indeterminate). Echocardiography (TTE or TOE): bedside tool for haemodynamically unstable patients when CTPA is not immediately feasible; identifies RV dilatation, RV hypokinesia (McConnell's sign — apical sparing), tricuspid regurgitation, elevated RVSP, and sometimes direct thrombus-in-transit. Lower limb venous duplex ultrasound: identifies DVT in 30-50% of PE patients; positive DVT with high clinical probability is sufficient justification for anticoagulation without CTPA in some scenarios. Arterial blood gas (ABG): hypoxaemia (PaO2 below 10 kPa), respiratory alkalosis (low PaCO2 from hyperventilation), widened A-a gradient. ECG: most common finding is sinus tachycardia; RBBB, S1Q3T3, AF, right axis deviation. Troponin I/T and BNP/NT-proBNP: elevated in submassive and massive PE (RV injury) — guide risk stratification and decision for intensified treatment.

Immediate anticoagulation is the mainstay of PE treatment — prevents thrombus extension, facilitates endogenous thrombolysis, and prevents recurrence. For haemodynamically stable PE: direct oral anticoagulants (DOACs) are first-line per NICE NG158 and ESC guidelines: apixaban (Eliquis) — 10 mg twice daily for 7 days, then 5 mg twice daily for 3-6 months (AMPLIFY trial — non-inferior to LMWH/warfarin with significantly fewer major bleeds); rivaroxaban (Xarelto) — 15 mg twice daily with food for 21 days, then 20 mg daily (EINSTEIN-PE trial). Advantages of DOACs over LMWH/warfarin: oral administration (no injections), no INR monitoring, faster onset of action, fixed dosing. Exceptions where LMWH/warfarin or LMWH alone preferred: active cancer (LMWH preferred — CLOT trial showed superiority over warfarin; edoxaban 60 mg daily also validated in SELECT-D trial for cancer-associated VTE); antiphospholipid syndrome (DOAC inferior to warfarin in triple-positive APS — use warfarin with INR 2.5-3.5); pregnancy (LMWH preferred — DOACs and warfarin contraindicated); severe renal impairment (eGFR below 15 — unfractionated heparin IV). Duration of anticoagulation: provoked PE (following identifiable transient risk factor — surgery, immobility, oestrogen) — minimum 3 months then discontinue; unprovoked PE (no identifiable trigger) — 3-6 months minimum; consider extended anticoagulation (indefinite low-dose apixaban 2.5 mg twice daily per AMPLIFY-EXT trial, or rivaroxaban 10 mg daily per EINSTEIN CHOICE) in unprovoked PE with low bleeding risk as recurrence risk is high (up to 30% at 5 years); cancer-associated VTE — anticoagulate indefinitely while cancer is active. Haemodynamically unstable (massive) PE: systemic thrombolysis is first-line for confirmed massive PE with cardiac arrest or haemodynamic collapse — alteplase 100 mg IV over 2 hours (50 mg bolus if cardiac arrest); achieves pulmonary artery recanalisation within 30-60 minutes; reduces mortality but increases major haemorrhage risk (including intracranial haemorrhage 1-2%) — absolute contraindications include recent stroke, active bleeding, and recent major surgery. Surgical embolectomy (cardiopulmonary bypass) or catheter-directed therapy (CDT): for massive PE where thrombolysis is contraindicated or has failed; CDT delivers thrombolytic agent directly into the pulmonary arteries at low dose (reducing systemic haemorrhage risk) — ultrasound-assisted CDT (EkoSonic — ULTIMA trial) reduces RV/LV ratio more effectively than anticoagulation alone in intermediate-risk PE. Outpatient treatment of low-risk PE: sPESI score of 0 (absence of malignancy, cardiopulmonary disease, HR above 110, SBP below 100, SpO2 below 90%, age above 80) identifies patients suitable for early discharge and oral DOAC therapy at home.

Acute complications: death — massive PE carries 30-50% acute mortality without prompt treatment; haemodynamic collapse and cardiac arrest (PEA); right ventricular failure from acute pulmonary hypertension (acute cor pulmonale); paradoxical embolism through a patent foramen ovale (PFO) causing simultaneous stroke. Chronic complications: post-PE syndrome (formerly post-thrombotic syndrome) — persistent breathlessness, exercise intolerance, and reduced quality of life after acute PE despite adequate anticoagulation; affects 30-50% of PE survivors; caused by incomplete vascular recanalisation and altered pulmonary haemodynamics. Chronic thromboembolic pulmonary hypertension (CTEPH): the most serious long-term complication — occurs in approximately 0.5-3.8% of PE survivors; unresolved thrombus organises and fibroses in the pulmonary arteries causing progressive fixed pulmonary hypertension and progressive right heart failure; presents with progressive breathlessness and exercise intolerance 6-24 months post-PE; diagnosed by V/Q scan (showing mismatched perfusion defects persisting at 3-6 months after anticoagulation) and right heart catheterisation; potentially curative treatment: pulmonary endarterectomy (PEA surgery — removes organised thrombus from pulmonary arteries; the gold standard for operable CTEPH — performed in specialist centres); riociguat (soluble guanylate cyclase stimulator) and macitentan for inoperable CTEPH; balloon pulmonary angioplasty (BPA) — catheter-based alternative to PEA for inoperable or residual disease. Recurrent VTE: the most common complication in inadequately anticoagulated patients; 5-year recurrence rate after discontinuing anticoagulation is 30% for unprovoked PE. Anticoagulation complications: major bleeding (intracranial haemorrhage — most feared; GI bleeding — most common); DOAC reversal agents: andexanet alfa (reverses factor Xa inhibitors — apixaban, rivaroxaban; approved 2019); idarucizumab (reverses dabigatran — approved).

VTE prophylaxis in hospitalised medical patients: LMWH (enoxaparin 40 mg SC once daily or dalteparin 5000 IU SC once daily) for 7-10 days or duration of immobility — recommended for acutely ill medical patients with VTE risk factors (PADUA score above 4) and no contraindication to anticoagulation; patients with bleeding risk too high for LMWH — mechanical prophylaxis only (anti-embolism stockings, intermittent pneumatic compression — IPC devices shown to reduce PE risk by 60%). VTE prophylaxis after surgery: LMWH initiated pre-operatively (orthopaedic) or 6-12 hours post-operatively (general surgery); extended prophylaxis for 28-35 days after major hip or knee arthroplasty and 28 days after major abdominal/pelvic cancer surgery per NICE NG89. DOACs for surgical VTE prophylaxis: apixaban (2.5 mg BD) or rivaroxaban (10 mg daily) for hip/knee replacement — equally effective to LMWH with easier oral administration. Travel-associated VTE prevention: for journeys above 4 hours — compression stockings (grade 2), adequate hydration, regular leg exercises, brief walks during the flight; LMWH for single-dose prophylaxis in those with known VTE risk factors on journeys above 6 hours. OCP and VTE: assess and counsel women with VTE risk factors about the risk of oestrogen-containing OCP — switch to progestogen-only pill or non-hormonal contraception; desogestrel-containing OCP carries 6-fold VTE risk vs. 3-fold for levonorgestrel-containing OCP. Thrombophilia screening: indicated for unprovoked VTE in patients under 50 (test family members); DVT in unusual sites (hepatic, portal, cerebral, renal veins); recurrent VTE. Antiphospholipid syndrome: confirmed APS with prior VTE requires lifelong anticoagulation with warfarin (INR 2-3). Secondary prevention after unprovoked PE: indefinite extended anticoagulation with low-dose apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily if bleeding risk is acceptable — reduces recurrence by 80-90% vs. aspirin.

Call 999 or go to A&E immediately for: sudden onset breathlessness with chest pain, particularly pleuritic (sharp pain worsening with breathing), or haemoptysis (coughing up blood) — these are the classic symptoms of pulmonary embolism; collapse or loss of consciousness (syncope) with breathlessness in a person with known VTE risk factors; any patient who is haemodynamically unstable (very low blood pressure, rapid heart rate, extreme breathlessness, cyanosis) and may have PE — this is a life-threatening emergency requiring emergency CTPA and consideration of thrombolysis. See a GP or attend A&E urgently for: unexplained leg swelling, redness, and pain with breathlessness — DVT with possible PE; breathlessness that develops over hours to days (subacute PE); breathlessness in a patient with known active cancer, recent surgery, prolonged immobility, pregnancy, or use of the OCP. Do not delay assessment — PE can be fatal within minutes to hours without treatment. Wells score assessment in A&E determines whether D-dimer testing is sufficient to exclude PE or whether CTPA is required. All patients with PE should have a thrombophilia screen and consideration of investigation for underlying malignancy (particularly for unprovoked PE).