Pulmonary Embolism and DVT

Stasis-predominant (largely modifiable)

• Immobility: hospitalization, ICU stay, post-op bed rest, cast/limb immobilization, long-haul travel (classically flights over several hours). Calf muscle pump failure allows thrombus nucleation in soleal sinuses.
• Anatomic venous compression: May–Thurner syndrome (left common iliac vein compressed by right common iliac artery → left leg DVT in a young woman); Paget–Schroetter effort thrombosis of the subclavian vein in throwers/weightlifters.
• Obesity and heart failure: reduced venous return plus low-grade prothrombotic inflammation.

Endothelial injury (modifiable)

• Surgery and trauma: orthopedic hip/knee arthroplasty, hip fracture, major abdominopelvic and neurosurgery carry the highest surgical risk.
• Indwelling catheters: the dominant cause of upper-extremity DVT; also IV drug use.

Hypercoagulable — acquired (mostly modifiable)

• Malignancy: tissue-factor–bearing tumors (adenocarcinoma of pancreas, lung, GI, ovary); migratory superficial thrombophlebitis is the classic Trousseau stem.
• Estrogen exposure: combined oral contraceptives, hormone therapy, tamoxifen; risk is multiplicative with factor V Leiden.
• Pregnancy and postpartum: peak risk is the postpartum period; cesarean delivery adds surgical risk (ACOG).
• Antiphospholipid syndrome, nephrotic syndrome, HIT, myeloproliferative neoplasms (JAK2), PNH, and smoking.

Non-modifiable

• Prior VTE: the single strongest predictor of recurrence.
• Advancing age and first-degree family history.
• Inherited thrombophilia: factor V Leiden is the most common in patients of European descent; antithrombin deficiency is the most thrombogenic and produces apparent heparin resistance.

• Venous stasis: Reduced blood flow in venous systems—most commonly in the deep veins of the lower extremities (soleal and gastrocnemius veins) due to immobility, surgery, or venous obstruction—allows platelets and coagulation factors to accumulate locally, promoting thrombus nucleation and propagation.

• Endothelial injury: Direct vessel wall damage from trauma, surgery, central venous catheters, or inflammatory conditions (malignancy, infection) exposes tissue factor and von Willebrand factor, triggering platelet adhesion and the extrinsic coagulation cascade.

• Hypercoagulability (acquired or inherited): Acquired states include malignancy (tissue factor expression), surgery/trauma (systemic inflammation, immobility), oral contraceptives and hormone therapy (increased factors II, VII, IX, X and decreased protein S), pregnancy (increased factors, decreased protein S), nephrotic syndrome (loss of anticoagulants), and antiphospholipid syndrome. Inherited thrombophilias include Factor V Leiden (resistance to protein C), prothrombin G20210A mutation, protein C deficiency, protein S deficiency, and antithrombin deficiency.

• PE pathophysiology: When a thrombus dislodges and travels through the venous system to lodge in the pulmonary arteries, it causes acute increases in right ventricular afterload (mechanical obstruction), release of vasoactive mediators (serotonin, thromboxane), and ventilation-perfusion (V/Q) mismatch. Massive PE (>50% vascular obstruction) can cause acute right heart failure, cardiogenic shock, and cardiovascular collapse.

DVT Presentations

• Unilateral leg swelling (most common finding)—occurs due to venous obstruction and increased capillary hydrostatic pressure with fluid extravasation into interstitial spaces; asymmetry is key (>3 cm circumference difference at homologous points suggests DVT).
• Leg pain and warmth—calf or thigh tenderness exacerbated by dorsiflexion (Homan's sign, though nonspecific); erythema may indicate superficial thrombophlebitis or cellulitis.
• Pitting edema and prominent superficial veins—reflects impaired venous return and collateral vein distension.
• Classic triad: swelling, pain, erythema occurring over hours to days; note that up to 50% of patients with proximal DVT have no symptoms ("silent DVT"), discovered incidentally on imaging.

PE Presentations (highly variable based on extent of obstruction and cardiopulmonary reserve)

• Dyspnea (most common symptom in ~85% of cases)—acute onset, often at rest or with minimal exertion; reflects V/Q mismatch and increased dead space ventilation.
• Pleuritic chest pain (37-49% of cases)—sharp, worse with deep breathing; suggests peripheral/pleural involvement and indicates smaller, distal emboli with better prognosis than massive PE.
• Hemoptysis (7% of cases)—indicates pulmonary infarction from peripheral emboli in the distribution of occluded vessels; relatively rare and suggests hemorrhagic pulmonary edema.
• Syncope or presyncope (5-18% of cases, depending on PE severity)—suggests massive PE with acute RV failure and decreased cardiac output; high mortality if not immediately recognized.
• Sudden cardiac arrest—occurs in fulminant PE; may present as pulseless electrical activity (PEA).
• Tachycardia and tachypnea—neurogenic response and compensation for hypoxemia; virtually universal in significant PE.
• Clinical Pearl: PE has a non-specific presentation; always maintain high suspicion, particularly in hospitalized, immobile, or postoperative patients. A patient with dyspnea + leg swelling should be considered PE until proven otherwise.

Clinical Risk Stratification (Essential First Step)

• Wells Criteria for PE (most commonly used in North America): assigns points for clinical findings (leg swelling, HR >100, immobility, prior VTE, hemoptysis, clinical signs of DVT, malignancy) to stratify into low (<2 points), intermediate (2-6 points), or high (>6 points) probability; guides subsequent testing strategy.
• PERC criteria (Pulmonary Embolism Rule-out Criteria): if all 8 criteria are negative (age <50, HR <100, SpO₂ ≥95%, no leg swelling, no hemoptysis, no pain with palpation, no clinical signs of DVT, no prior PE/DVT), PE can be excluded without further testing in low-risk patients (90% sensitivity).

Laboratory/Imaging Diagnostics

• D-dimer (highly sensitive, low specificity): detects fibrin degradation products; negative D-dimer effectively rules out VTE with >99% sensitivity (NPV) if clinical suspicion is low/intermediate; however, elevated in pregnancy, infection, malignancy, and post-operatively, limiting specificity. Do NOT use in high-clinical-suspicion patients; order imaging instead.
• Contrast-enhanced CT pulmonary angiography (CTPA) (gold standard for PE diagnosis): 94-98% sensitivity and specificity for central/segmental PEs; allows assessment of right ventricular strain (RV/LV ratio >0.9 indicates RV dilatation), excludes other diagnoses (pneumonia, aortic dissection), and is first-line imaging if PE is suspected regardless of Wells score or D-dimer.
• Ventilation-perfusion (V/Q) scan: alternative to CTPA when CT is contraindicated (renal failure, contrast allergy) or for suspected PE in pregnancy (lower radiation to fetus than CTPA); high probability scan (perfusion defects without matched ventilation defects) confirms PE; normal scan excludes PE; intermediate results require additional testing.
• Compression ultrasound (CUS) of lower extremities: first-line test for DVT diagnosis; 95% sensitive/specific for proximal DVT (popliteal/femoral veins) when performed by trained operators; less sensitive for distal DVT (calf veins) and asymptomatic DVT. Positive proximal DVT on CUS can be treated as PE equivalent without CTPA in some clinical scenarios.
• Electrocardiogram (ECG): nonspecific in PE; classic finding of sinus tachycardia with T-wave inversion in leads V1-V4 ("classic" but rare); also may show right axis deviation, right heart strain pattern, or atrial fibrillation; primarily useful to exclude MI and other cardiopulmonary conditions.
• Chest X-ray (CXR): often normal or nonspecific; may show Hampton's hump (wedge-shaped consolidation from pulmonary infarction, rare), atelectasis, or pleural effusion; useful to exclude pneumonia and pneumothorax.
• Troponin and natriuretic peptides (BNP/NT-proBNP): elevated in PE with RV strain; indicate worse prognosis but are not diagnostic for VTE; used for risk stratification.
• Arterial blood gas (ABG): may show hypoxemia with respiratory alkalosis (hyperventilation from compensation) and elevated A-a gradient; normal ABG does NOT exclude PE.
• Diagnostic Pearl for Exams: **D-d

Stabilization of high-risk PE

• Oxygen and cautious volume: give only modest fluid — the failing RV is preload-sensitive but easily over-distended, worsening septal shift and LV filling.
• Vasopressors: norepinephrine first-line to restore coronary perfusion of the ischemic RV.
• Systemic thrombolysis: alteplase, given for hemodynamically unstable PE (AHA; CHEST 2021). Absolute contraindications include prior intracranial hemorrhage, ischemic stroke within 3 months, known intracranial neoplasm or vascular malformation, active bleeding, and recent head trauma or intracranial surgery.
• If thrombolysis fails or is contraindicated: catheter-directed thrombolysis/thrombectomy or surgical embolectomy; VA-ECMO as a bridge.

Anticoagulation — first-line for everyone without contraindication

• Direct oral anticoagulants: apixaban or rivaroxaban (both with a loading phase, no parenteral lead-in); dabigatran and edoxaban require 5 days of parenteral bridging. CHEST 2021 and ASH 2020 prefer DOACs over warfarin for most patients.
• Low-molecular-weight heparin: enoxaparin — preferred in pregnancy (ACOG; DOACs and warfarin are contraindicated) and a reasonable choice in cancer-associated VTE.
• Unfractionated heparin: use when hemodynamic instability, thrombolysis, or procedures are anticipated, and in CrCl <30 mL/min — short half-life, reversible with protamine.
• Warfarin: reserved for antiphospholipid syndrome (DOACs inferior), mechanical valves, and severe renal impairment; overlap with parenteral agent ≥5 days until INR ≥2.

Duration and definitive care

• 3 months for VTE provoked by a major transient risk factor; extended/indefinite therapy for unprovoked VTE, recurrent VTE, or active cancer.
• IVC filter: only when anticoagulation is absolutely contraindicated (active bleeding); use a retrievable device and start anticoagulation once safe. Filters do not treat clot.
• Outpatient management is appropriate for low-risk PE (sPESI 0 / Hestia-negative).

Complications of the disease

• Obstructive shock and sudden death (emergency): abrupt RV afterload rise → RV dilation, septal bowing, reduced LV preload. Signals are hypotension, JVD, and McConnell's sign (RV free-wall hypokinesis with apical sparing) on bedside echo; cardiac arrest is typically PEA.
• Pulmonary infarction: peripheral emboli beyond bronchial collateral supply → pleuritic pain, hemoptysis, Hampton's hump; more common in patients with poor cardiopulmonary reserve.
• Chronic thromboembolic pulmonary hypertension (CTEPH): failure of clot resolution with fibrotic organization → progressive exertional dyspnea and a loud P2 months after PE. Screen with V/Q scan (more sensitive than CTPA); definitive therapy is pulmonary thromboendarterectomy.
• Recurrent VTE, especially after stopping anticoagulation for unprovoked events.
• Paradoxical embolism: right-to-left shunt across a patent foramen ovale when RA pressure rises → stroke or arterial occlusion.
• Post-thrombotic syndrome: valvular incompetence after proximal DVT → chronic limb heaviness, edema, hyperpigmentation, venous ulceration.
• Phlegmasia cerulea dolens (emergency): near-total iliofemoral outflow occlusion → massively swollen, cyanotic, painful limb with compartment syndrome and venous gangrene; requires thrombolysis or thrombectomy.

Complications of treatment

• Major bleeding, including intracranial hemorrhage (emergency): highest with systemic thrombolysis. Reverse with 4-factor PCC plus vitamin K for warfarin, idarucizumab for dabigatran, andexanet alfa for factor Xa inhibitors, protamine for heparin.
• Heparin-induced thrombocytopenia (emergency): PF4–heparin antibodies cause platelet activation with a platelet drop typically 5–10 days after exposure and thrombosis, not bleeding. Stop all heparin, start a non-heparin anticoagulant (argatroban); do not start warfarin alone (venous limb gangrene) and avoid prophylactic platelet transfusion.
• Warfarin-induced skin necrosis: early protein C depletion, classically unmasking protein C deficiency.
• IVC filter complications: filter thrombosis, migration, caval perforation, and increased recurrent DVT if left in place.

• Hemodynamically unstable + suspected PE → do not send the patient to CT. Get a bedside echocardiogram; RV dilation with McConnell's sign plus shock justifies empiric thrombolysis (AHA statement on massive PE).
• The single best next step in a stable patient hinges on pretest probability. Low/intermediate Wells → D-dimer (age-adjusted thresholds are validated in patients over 50); high Wells → go straight to CTPA and start empiric anticoagulation while awaiting imaging if bleeding risk is low.
• The most common ECG finding is sinus tachycardia, not S1Q3T3. S1Q3T3 and T-wave inversions in V1–V4 are the classic buzzwords but are insensitive — their absence never excludes PE, and their presence is not diagnostic.
• Pregnancy: LMWH throughout; warfarin is teratogenic and DOACs are not recommended (ACOG). Remember that all ACE inhibitors, captopril included, are separately contraindicated in pregnancy — a favorite cross-topic distractor.
• Submassive (intermediate-risk) PE is not an automatic thrombolysis case. PEITHO showed fewer episodes of hemodynamic decompensation but more major bleeding and stroke with full-dose systemic lysis; CHEST reserves it for those who deteriorate on anticoagulation.
• The one association examiners love: unprovoked VTE plus migratory superficial thrombophlebitis → occult adenocarcinoma (Trousseau). Pursue age- and sex-appropriate cancer screening, not an indiscriminate whole-body work-up.
• Falling platelets on day 5–10 of heparin with new clot = HIT. Stop heparin, start argatroban; do not simply switch to warfarin and do not transfuse platelets.
• An IVC filter is a bridge, not a therapy — indicated only when anticoagulation is absolutely contraindicated, and it should be retrieved once anticoagulation can begin.
• A negative D-dimer in a high-probability patient is a trap: it does not rule out PE. Image.