Cardiovascular

Pulmonary embolism: risk stratification (PESI) and management

Clinical Overview and When to Suspect Pulmonary Embolism

— ~900,000 VTE events/year in the US; PE is the third most common cardiovascular cause of death after MI and stroke.

— 30-day mortality ranges from <1% (low-risk) to >50% (high-risk with cardiac arrest).

— Up to 50% of untreated proximal DVTs embolize.

— Acute unexplained dyspnea, pleuritic chest pain, tachycardia, hypoxia, syncope, or hemoptysis.

— Unexplained sinus tachycardia in a postoperative, hospitalized, or immobilized patient.

— Syncope with hypoxia or RV strain features — PE is a frequently missed cause.

— Hypotension or shock without clear cardiac/sepsis etiology + clear lungs.

— Stasis: immobilization >3 days, long travel, recent surgery (especially orthopedic), stroke with paresis.

— Endothelial injury: trauma, surgery, central venous catheters, prior DVT.

— Hypercoagulability: active malignancy, pregnancy/postpartum (up to 6 weeks), estrogen/OCPs, nephrotic syndrome, inflammatory bowel disease, inherited thrombophilias (Factor V Leiden, prothrombin G20210A, protein C/S or antithrombin deficiency), antiphospholipid syndrome.

Definition: Obstruction of pulmonary arterial vasculature by thrombus, most commonly embolized from deep veins of the lower extremities or pelvis. Less commonly from upper-extremity DVT (catheter-associated), right heart thrombus, or tumor/fat/air.

Epidemiology and burden:

Pretest probability triggers — when to suspect PE:

Risk factors (Virchow triad framework):

Provoked vs unprovoked: Major determinant of anticoagulation duration. Provoked = identifiable transient (surgery, trauma, immobilization within 90 days) or persistent (cancer) risk factor.

Board pearl: A young woman on OCPs presenting with pleuritic chest pain and unexplained sinus tachycardia after a transatlantic flight is the classic stem — PE is the answer even if SpO₂ is normal, because a normal pulse oximetry does NOT rule out PE.

Step 3 management: In the ambulatory setting, suspected PE mandates same-day evaluation in an ED or facility capable of CTPA — never schedule outpatient workup for active suspicion.

Presentation Patterns and Key History

— Pleuritic chest pain (~50%), dyspnea (~75%), hemoptysis (<10%).

— Most patients have only 1–2 nonspecific symptoms; absence of the triad does not exclude PE.

— Pulmonary infarction syndrome: pleuritic pain + hemoptysis + low-grade fever — peripheral, smaller emboli causing distal infarction. Often mimics pneumonia.

— Isolated dyspnea syndrome: sudden dyspnea without pain — more central/submassive PE, higher mortality risk.

— Circulatory collapse syndrome: syncope, presyncope, hypotension, cardiac arrest — large central or saddle PE with RV failure.

— Onset (acute vs subacute — most PEs evolve over hours).

— Recent surgery within 90 days (especially orthopedic, pelvic, neurosurgery).

— Immobilization >3 days, recent long travel (>6–8 hours).

— Active or recent cancer, ongoing chemotherapy, central venous access.

— Estrogen-containing contraceptives, hormone replacement, tamoxifen.

— Pregnancy/postpartum status; recent miscarriage (think APS).

— Prior VTE, family history of VTE in first-degree relatives <50.

— Smoking, obesity (BMI >30), inflammatory disease flare.

— Clinical signs of DVT (3), PE most likely diagnosis (3), HR >100 (1.5), immobilization/surgery <4 wk (1.5), prior DVT/PE (1.5), hemoptysis (1), malignancy (1).

— >4 = "PE likely" → CTPA. ≤4 = "PE unlikely" → D-dimer first.

Classic symptom triad (rarely all present):

Symptom clusters by clinical syndrome:

Key history points to elicit:

Wells criteria for PE (pretest probability):

PERC rule (age-adjusted in low-pretest-probability patients): All 8 criteria negative (age <50, HR <100, SpO₂ ≥95%, no hemoptysis, no estrogen, no prior VTE, no recent surgery/trauma, no unilateral leg swelling) → PE effectively excluded without D-dimer.

Key distinction: Wells "PE most likely diagnosis" is subjective gestalt — a positive feature when you've considered and excluded other causes. This subjective item drives most of the score's predictive power.

Board pearl: Postpartum patient with sudden dyspnea + tachycardia 2 weeks after C-section = PE until proven otherwise. Pregnancy/postpartum is hypercoagulable up to 6 weeks postpartum.

Physical Exam Findings and Hemodynamic Assessment

— Tachycardia (HR >100): most common abnormal finding, present in ~40%.

— Tachypnea (RR >20): present in ~70%; often the only objective sign.

— Hypoxemia (SpO₂ <95% on room air): supports diagnosis but 20–25% of confirmed PE have normal SpO₂.

— Hypotension (SBP <90 or drop ≥40 from baseline for >15 min): defines high-risk (massive) PE.

— Fever: usually low-grade; high fever should redirect toward pneumonia.

— Clear lungs in the setting of hypoxia/dyspnea — a major clue to PE (vs pneumonia/CHF).

— Loud P2, fixed split S2, right-sided S3/S4 — pulmonary hypertension and RV strain.

— Elevated JVP, parasternal heave, tricuspid regurgitation murmur — RV pressure overload.

— Pleural friction rub if pulmonary infarction present.

— Unilateral leg swelling, calf tenderness, warmth, asymmetric calf diameter (>3 cm difference at 10 cm below tibial tuberosity).

— Homan sign is insensitive and nonspecific — do not rely on it.

— Up to 50% of PE patients have NO clinical signs of DVT.

— High-risk (massive) PE: sustained hypotension, shock, cardiac arrest, or need for vasopressors. ~5% of PE; mortality 25–50%.

— Intermediate-risk (submassive): normotensive BUT RV dysfunction (echo/CT) AND/OR elevated troponin/BNP. ~30–40%; mortality 3–15%.

— Low-risk: normotensive, no RV dysfunction, normal biomarkers. ~55%; mortality <1%.

— RV:LV ratio >1.0, septal flattening ("D-sign"), McConnell sign (RV free wall hypokinesis with apical sparing), TAPSE <17 mm.

Vital signs — the cornerstone of severity assessment:

Cardiopulmonary exam:

Lower extremity exam:

Hemodynamic categorization (foundational for triage):

Bedside ultrasound findings (POCUS):

CCS pearl: On the CCS case, order continuous pulse oximetry, telemetry, and serial BPs immediately on any PE suspicion — hemodynamic deterioration can occur within minutes, and you'll be evaluated on monitoring orders.

Board pearl: A normotensive PE patient with elevated troponin + RV dilation on echo is intermediate-high risk — these patients warrant ICU-level monitoring even without overt shock.

Diagnostic Workup — Initial Labs, Imaging, ECG, Biomarkers

— High sensitivity (~95%), low specificity (~40%). Useful only to rule out PE.

— Threshold: <500 ng/mL (FEU) excludes PE in low or intermediate pretest probability patients.

— Age-adjusted D-dimer (age × 10 ng/mL for patients >50): increases specificity without losing sensitivity. Use in low/intermediate pretest probability.

— YEARS algorithm: if no clinical DVT signs, no hemoptysis, and PE not most likely → D-dimer threshold raised to 1000 ng/mL.

— Do not order D-dimer in high pretest probability — go straight to CTPA.

— False positives: malignancy, pregnancy, sepsis, postoperative state, age >70, inflammation.

— Hypoxemia, hypocapnia, respiratory alkalosis, increased A–a gradient.

— Normal ABG does not exclude PE.

— Sinus tachycardia — most common (~40%).

— S1Q3T3 pattern — classic but only ~20% (deep S in I, Q wave + T inversion in III).

— T-wave inversions in V1–V4 (right precordial leads) — best ECG sign of RV strain.

— New right bundle branch block, right axis deviation, P pulmonale.

— Most often normal or nonspecific.

— Westermark sign: focal oligemia distal to embolism.

— Hampton hump: wedge-shaped pleural-based opacity (infarction).

— Fleischner sign: enlarged central pulmonary artery.

— Primary role: exclude alternatives (pneumonia, pneumothorax, CHF).

— Troponin elevation → RV myocyte injury; associated with worse outcomes.

— BNP/NT-proBNP elevation → RV stretch; integral to intermediate-risk classification.

— Both feed into PESI/sPESI–biomarker–imaging algorithm for triage.

D-dimer (ELISA, quantitative):

ABG (not required but informative):

ECG (the buzzword exam):

CXR:

Cardiac biomarkers (risk stratification, NOT diagnostic):

Step 3 management: When pretest probability is high (Wells >6), do not delay anticoagulation for imaging — start empiric heparin while arranging CTPA, provided bleeding risk is acceptable.

Board pearl: A negative D-dimer in a high-Wells patient does NOT exclude PE — sensitivity is insufficient at high prevalence. Proceed to CTPA.

Diagnostic Workup — Advanced or Confirmatory Studies

— Sensitivity ~83%, specificity ~96% (PIOPED II).

— Direct visualization of filling defects in pulmonary arteries down to subsegmental level.

— Simultaneously assesses RV:LV ratio (≥1.0 = RV dysfunction, prognostic).

— Also evaluates alternative diagnoses (pneumonia, dissection, malignancy).

— Contraindications: severe contrast allergy, severe renal failure (eGFR <30 — relative), pregnancy (relative).

— Preferred when: pregnancy (lower fetal radiation than CTPA to maternal breast tissue debate, but lower breast dose with V/Q), severe contrast allergy, severe CKD, young women.

— Results: normal/very low (excludes PE), low/intermediate (nondiagnostic — requires further workup), high probability (confirms PE in high-pretest-probability patients).

— Limitation: indeterminate in ~50% of patients with abnormal baseline CXR or COPD.

— Used when CTPA is contraindicated or nondiagnostic; positive proximal DVT in a patient with PE symptoms is sufficient to treat for PE.

— Particularly useful in pregnancy as a first imaging step.

— Historical gold standard; now rarely used diagnostically — reserved for procedures (catheter-directed thrombolysis/embolectomy).

— Not a primary diagnostic test for PE (sensitivity only ~50%).

— Critical for risk stratification in confirmed PE: RV dilation, hypokinesis, McConnell sign, septal flattening, TAPSE, PA pressure estimation.

— In unstable patients, bedside echo showing RV strain + clinical picture is sufficient to justify thrombolysis even without CTPA.

— Defer in acute setting (anticoagulation alters protein C/S, antithrombin levels; acute thrombus elevates D-dimer/factor VIII).

— Consider in: unprovoked PE in patient <50, recurrent unprovoked VTE, unusual site thrombosis, strong family history.

— Test antiphospholipid antibodies (lupus anticoagulant, anti–β2-glycoprotein I, anticardiolipin) before stopping anticoagulation.

CT pulmonary angiography (CTPA) — gold standard:

V/Q scan — alternative when CTPA contraindicated:

Lower extremity compression ultrasound:

Pulmonary angiography (catheter-based):

Echocardiography:

MR pulmonary angiography: Limited availability and sensitivity; not first-line.

Hypercoagulability workup:

Key distinction: CTPA confirms PE; echo risk-stratifies it. Don't conflate the two — a normal echo does NOT exclude PE.

CCS pearl: Order CTPA early in the case; advancing simulated clock without confirmatory imaging in a stable patient will count against you.

Risk Stratification — PESI and Management Logic

— Variables (points = age in years +): male (+10), cancer (+30), heart failure (+10), chronic lung disease (+10), HR ≥110 (+20), SBP <100 (+30), RR ≥30 (+20), temp <36°C (+20), altered mental status (+60), SaO₂ <90% (+20).

— Class I (≤65): very low risk, 0–1.6% mortality.

— Class II (66–85): low risk, 1.7–3.5%.

— Class III (86–105): intermediate, 3.2–7.1%.

— Class IV (106–125): high, 4.0–11.4%.

— Class V (>125): very high, 10–24.5%.

— 1 point each for: age >80, history of cancer, chronic cardiopulmonary disease, HR ≥110, SBP <100, SaO₂ <90%.

— sPESI = 0 → low risk (1% mortality, outpatient candidate).

— sPESI ≥1 → not low risk (≥10.9% mortality).

— High-risk: hemodynamic instability (shock/hypotension) → systemic thrombolysis.

— Intermediate-high-risk: PESI III–V or sPESI ≥1 AND RV dysfunction AND elevated troponin → admit, monitor closely, consider rescue thrombolysis.

— Intermediate-low-risk: PESI III–V or sPESI ≥1 AND (RV dysfunction OR elevated troponin, not both) → admit for monitored anticoagulation.

— Low-risk: PESI I–II or sPESI = 0, no RV dysfunction, normal biomarkers → consider outpatient management or early discharge.

Pulmonary Embolism Severity Index (PESI): Validates 30-day mortality risk and identifies candidates for outpatient management.

Simplified PESI (sPESI) — easier to remember:

ESC integrated risk stratification (gold standard framework):

HESTIA criteria (outpatient eligibility — must answer NO to all): hemodynamic instability, need for thrombolysis/embolectomy, active bleeding, O₂ requirement to maintain SaO₂ >90%, PE on anticoagulation, severe pain requiring IV analgesia, social/medical reason for admission >24h, CrCl <30, severe liver dysfunction, pregnancy, history of HIT.

Step 3 management: A hemodynamically stable patient with sPESI = 0, normal troponin, no RV strain, reliable follow-up, and access to anticoagulation can be discharged home from the ED on a DOAC — increasingly favored, cost-effective, guideline-endorsed.

Board pearl: PESI/sPESI predicts mortality; HESTIA determines outpatient suitability. Both required for safe disposition decisions.

Pharmacotherapy — First-Line Anticoagulation

— Apixaban: 10 mg BID × 7 days → 5 mg BID. No parenteral lead-in. Preferred in renal impairment (used down to CrCl 15, with dose adjustment).

— Rivaroxaban: 15 mg BID × 21 days → 20 mg daily with food. No lead-in. Avoid CrCl <30.

— Dabigatran: Requires 5–10 days of parenteral lead-in (LMWH), then 150 mg BID. Avoid CrCl <30. Reversible with idarucizumab.

— Edoxaban: Requires 5–10 days of parenteral lead-in, then 60 mg daily (30 mg if CrCl 15–50 or weight ≤60 kg).

— Enoxaparin 1 mg/kg SC q12h or 1.5 mg/kg SC daily.

— First-line in: pregnancy, active cancer (though DOACs increasingly used in non-GI/GU cancers), severe obesity (>120 kg consider weight-based with anti-Xa monitoring).

— Avoid in CrCl <30 (use UFH instead) or adjust dose.

— Indicated when: hemodynamic instability/possible thrombolysis, severe renal failure (CrCl <30), high bleeding risk requiring rapid reversal.

— Bolus 80 U/kg → 18 U/kg/hr; titrate to aPTT 1.5–2.5× control or anti-Xa 0.3–0.7.

— Now reserved for: antiphospholipid syndrome (triple-positive), mechanical heart valves, severe renal failure, DOAC contraindication, cost considerations.

— Requires bridging with LMWH/UFH until INR 2–3 for ≥24 hours and ≥5 days of overlap.

— DOACs (apixaban, rivaroxaban, edoxaban) non-inferior to LMWH for most solid tumors.

— LMWH preferred for luminal GI/GU malignancies (higher bleeding risk with DOACs).

— Andexanet alfa for apixaban/rivaroxaban major bleeding.

— Idarucizumab for dabigatran.

— 4-factor PCC for warfarin (plus IV vitamin K).

Direct oral anticoagulants (DOACs) — first-line for most patients:

Low-molecular-weight heparin (LMWH):

Unfractionated heparin (UFH):

Warfarin:

Cancer-associated thrombosis (CAT):

Bleeding risk assessment: Consider HAS-BLED, RIETE score; address modifiable factors (BP control, NSAID cessation, PPI for high GI risk).

Reversal agents:

Board pearl: Apixaban and rivaroxaban can be started without parenteral lead-in. Dabigatran and edoxaban CANNOT — they require 5–10 days of LMWH/UFH first.

Procedures — Thrombolysis, Embolectomy, and IVC Filters

— Alteplase (tPA) 100 mg IV over 2 hours is the standard regimen.

— Alternative: 0.6 mg/kg (max 50 mg) IV bolus over 15 min in cardiac arrest.

— Reduces mortality and recurrent PE in shock; NNT ≈ 20 in massive PE.

— Absolute contraindications: prior intracranial hemorrhage, ischemic stroke <3 months, known intracranial neoplasm/AVM, active bleeding, suspected aortic dissection, recent head/spine trauma or surgery <3 weeks.

— Relative contraindications: age >75, anticoagulation, pregnancy, recent major surgery <3 weeks, traumatic CPR, uncontrolled HTN (>180/110), recent GI bleeding.

— Routine thrombolysis NOT recommended (PEITHO trial: reduced hemodynamic decompensation but increased major bleeding and intracranial hemorrhage, especially in age >75).

— Reserve for rescue therapy if hemodynamic deterioration occurs.

— Catheter-directed thrombolysis (low-dose tPA, ~20–24 mg over 12–24 h) ± ultrasound assistance (EKOS).

— Mechanical/aspiration thrombectomy (FlowTriever, Indigo) — increasingly used; no thrombolytic drug, useful when lytics contraindicated.

— Indicated in high-risk PE with thrombolysis contraindication, or intermediate-high-risk PE with deterioration.

— Reserved for high-risk PE with contraindication to lytics AND failed/unavailable CDT, or large clot-in-transit/right heart thrombus.

— Requires cardiothoracic surgery and cardiopulmonary bypass.

— Bridge in refractory shock or cardiac arrest from massive PE while definitive therapy arranged.

— Indication: acute VTE with absolute contraindication to anticoagulation, or recurrent PE despite therapeutic anticoagulation.

— Use retrievable filters and remove once anticoagulation can be safely started.

— NOT indicated routinely in PE patients receiving anticoagulation (PREPIC-2 trial).

— Multidisciplinary team activation for intermediate-high and high-risk PE — improves time to therapy and outcomes.

Systemic thrombolysis — indication: high-risk (massive) PE:

Intermediate-high-risk PE:

Catheter-directed therapy (CDT):

Surgical embolectomy:

Extracorporeal life support (VA-ECMO):

IVC filters:

PERT (Pulmonary Embolism Response Team):

CCS pearl: For massive PE with shock, order: alteplase, ICU admission, vasopressors (norepinephrine first-line), continuous monitoring, fluids cautiously (avoid RV overload — small boluses ≤500 mL only).

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher baseline PE mortality, higher bleeding risk, higher prevalence of CKD.

— Apixaban is preferred DOAC due to favorable bleeding profile (especially GI bleeding vs rivaroxaban).

— Apixaban dose reduction (2.5 mg BID) if ≥2 of: age ≥80, weight ≤60 kg, creatinine ≥1.5 — but for VTE treatment, use full 5 mg BID regardless (dose reduction criteria apply to AFib, not VTE).

— Age-adjusted D-dimer (age × 10 ng/mL) improves specificity.

— Avoid systemic thrombolysis in age >75 unless massive PE — bleeding risk substantially higher.

— Falls assessment — recurrent falls are NOT an absolute contraindication to anticoagulation (benefit usually outweighs risk).

— CrCl ≥30: all DOACs acceptable; apixaban and rivaroxaban preferred.

— CrCl 15–29: apixaban acceptable with caution; rivaroxaban avoided; warfarin alternative.

— CrCl <15 or dialysis: warfarin (target INR 2–3) or UFH preferred; limited DOAC data, though apixaban is increasingly used off-label.

— Avoid LMWH at CrCl <30 (or dose-reduce with anti-Xa monitoring).

— Adjust dosing as renal function changes — recheck creatinine periodically.

— Child-Pugh A: all DOACs acceptable.

— Child-Pugh B: avoid rivaroxaban (contraindicated); apixaban with caution; dabigatran/edoxaban with caution.

— Child-Pugh C: avoid all DOACs. Use LMWH or warfarin (carefully — coagulopathy makes INR unreliable).

— Baseline coagulopathy does not equal anticoagulation — patients with cirrhosis still develop VTE and benefit from treatment.

— DOACs generally acceptable up to BMI 40 or weight 120 kg; emerging data support use beyond.

— LMWH: weight-based dosing with anti-Xa monitoring (target 0.6–1.0 IU/mL trough).

— Avoid fixed-dose LMWH in extreme obesity.

Elderly (>75 years):

Chronic kidney disease:

Hepatic impairment:

Obesity (BMI >40 or weight >120 kg):

Step 3 management: In a 78-year-old with CrCl 35 mL/min and new PE, start apixaban 10 mg BID × 7 days, then 5 mg BID. Avoid thrombolysis unless hemodynamically unstable.

Board pearl: VTE-treatment apixaban dosing is NOT reduced for age/weight/creatinine — that reduction applies only to atrial fibrillation indications.

Special Populations — Pregnancy and Postpartum

— VTE is a leading cause of maternal mortality in developed countries.

— Risk is elevated throughout pregnancy and highest in the first 6 weeks postpartum (up to 20× baseline).

— Cesarean delivery further increases risk.

— D-dimer is physiologically elevated in pregnancy — less useful, but a low D-dimer in early pregnancy with low pretest probability may still help rule out.

— YEARS-adjusted algorithm validated in pregnancy.

— Lower-extremity compression ultrasound first if DVT signs present — positive result avoids chest imaging.

— If pulmonary imaging needed: V/Q scan has lower maternal breast radiation than CTPA (concerning for breast cancer risk); CTPA has lower fetal radiation. Either is acceptable; choice depends on availability and chest x-ray findings.

— Shield the abdomen; both modalities are below teratogenic thresholds.

— LMWH is the anticoagulant of choice (enoxaparin 1 mg/kg SC q12h).

— Does not cross the placenta; safe for breastfeeding.

— Warfarin contraindicated — teratogenic (warfarin embryopathy in weeks 6–12), CNS abnormalities later; safe postpartum and during breastfeeding.

— DOACs contraindicated in pregnancy and breastfeeding — limited data, cross placenta.

— UFH acceptable, especially near delivery (shorter half-life).

— Transition from LMWH to UFH at 36 weeks or stop LMWH 24 hours before planned delivery/induction.

— Neuraxial anesthesia requires 24 hours since last therapeutic LMWH dose, 12 hours since prophylactic dose.

— Resume anticoagulation 6–12 hours after vaginal delivery, 12–24 hours after C-section.

— Continue for minimum 6 weeks postpartum AND total ≥3 months.

— Systemic thrombolysis is NOT absolutely contraindicated — use when life-threatening; alteplase does not cross placenta significantly.

— Catheter-directed therapy preferred when possible.

Epidemiology:

Diagnostic approach in pregnancy:

Treatment:

Peripartum management:

Massive PE in pregnancy:

Pediatrics (rare): Most pediatric PE is provoked (central lines, malignancy, congenital heart disease). LMWH first-line; pediatric DOAC data emerging (rivaroxaban, dabigatran approved).

Board pearl: A postpartum woman with dyspnea — start empiric LMWH while awaiting imaging. Never use warfarin or DOACs in pregnancy.

Complications and Adverse Outcomes

— Obstructive shock and cardiac arrest: RV failure from acute pressure overload; PEA is the most common arrest rhythm — consider PE in any unexplained PEA arrest.

— Pulmonary infarction: ~10% of PE, more common with peripheral emboli; presents with pleuritic pain, hemoptysis, fever.

— Refractory hypoxemia: V/Q mismatch, intrapulmonary shunting, possible right-to-left shunt through PFO.

— Paradoxical embolism: clot crosses PFO → systemic embolization (stroke); screen with echo if cryptogenic stroke + PE.

— Recurrent PE during anticoagulation: ~2% in first 6 months; investigate adherence, drug interactions, malignancy (consider workup if recurrent unprovoked).

— Major bleeding: ~2–3%/year on chronic anticoagulation. GI most common with rivaroxaban; intracranial hemorrhage less common with DOACs vs warfarin.

— Heparin-induced thrombocytopenia (HIT): platelet drop >50% or to <150 between days 4–14 after heparin exposure. Stop ALL heparin (including flushes), start non-heparin anticoagulant (argatroban, bivalirudin, fondaparinux). Do NOT give platelet transfusion (paradoxical thrombosis).

— Skin necrosis with warfarin (protein C deficiency, early warfarin without bridging).

— Chronic thromboembolic pulmonary hypertension (CTEPH): develops in 2–4% of PE survivors; presents months to years later with progressive dyspnea, RV failure. Diagnosis: V/Q scan (preferred screening), confirmed by right heart cath + pulmonary angiography. Curative treatment: pulmonary thromboendarterectomy (PTE) at expert center. Riociguat or balloon pulmonary angioplasty for inoperable cases.

— Post-PE syndrome: persistent dyspnea, reduced exercise tolerance, decreased quality of life in 30–50%; not always associated with measurable CTEPH.

— Recurrent VTE: annual risk after stopping anticoagulation: ~10% in first year after unprovoked PE; cumulative 30% at 5 years.

Acute complications:

Anticoagulation-related complications:

Chronic complications:

Step 3 management: Any PE survivor with persistent dyspnea at 3–6 months should be evaluated with echocardiography and V/Q scan to screen for CTEPH — this is a Step 3 favorite missed-diagnosis stem.

Board pearl: Platelet drop on day 5–10 of heparin = HIT until proven otherwise. Stop heparin, start argatroban, send HIT antibody/serotonin release assay, NO platelet transfusion.

When to Escalate Care — ICU, Consults, Inpatient Triage

— Outpatient management: sPESI = 0, HESTIA all negative, reliable follow-up, access to anticoagulation. Discharge from ED on DOAC with 24–72h follow-up.

— General ward admission: sPESI ≥1, hemodynamically stable, no RV dysfunction OR only one biomarker abnormality.

— Step-down/telemetry: intermediate-low risk with isolated troponin or RV strain.

— ICU admission: intermediate-high risk (RV dysfunction + biomarker elevation), high-risk (shock), need for thrombolysis or CDT, refractory hypoxemia.

— Hypotension or vasopressor requirement.

— Worsening hypoxemia (FiO₂ >50% to maintain SpO₂ ≥90%).

— Hemodynamic deterioration despite anticoagulation.

— Post-thrombolysis monitoring (24 hours).

— Cardiac arrest with ROSC.

— Massive PE.

— Submassive PE with RV dysfunction.

— High clot burden, saddle embolus.

— PE in pregnancy or postoperative period requiring intervention.

— Failure of initial anticoagulation.

— Interventional cardiology/radiology: for catheter-directed therapy.

— Cardiothoracic surgery: for surgical embolectomy or ECMO cannulation.

— Hematology: for HIT, recurrent VTE on anticoagulation, hypercoagulability workup, complex cases.

— Maternal-fetal medicine + OB: in pregnant patients.

— Pulmonology: for CTEPH follow-up, complex cases, IVC filter management.

— Fluids: small boluses (≤500 mL) ONLY — excess fluid worsens RV failure by increasing wall stress and septal bowing into LV.

— Vasopressors: norepinephrine first-line (maintains coronary perfusion to RV); dobutamine added for low cardiac output.

— Avoid intubation if possible — positive pressure ventilation reduces preload and can precipitate cardiac arrest. If required, use low tidal volumes, low PEEP, ketamine/etomidate induction.

— Inhaled pulmonary vasodilators (NO, epoprostenol) may improve RV afterload as bridge.

Disposition decision tree:

Indications for ICU transfer:

PERT activation criteria:

Consultants to involve:

Hemodynamic support priorities in massive PE:

CCS pearl: In an unstable PE case, order parallel actions: anticoagulation + ICU + cardiology consult + thrombolysis evaluation + echocardiogram — sequential ordering wastes simulated time.

Board pearl: Intubation of a massive PE patient is a high-risk maneuver — anticipate cardiac arrest and have vasopressors and ECMO team ready.

Key Differentials — Other Causes of Acute Dyspnea/Chest Pain

— Substernal pressure radiating to arm/jaw, diaphoresis, ECG ST changes, troponin elevation.

— Overlap: PE can cause troponin elevation and T-wave inversions in V1–V4 (RV strain) — distinguish by clinical context, lack of regional wall motion abnormalities (except RV in PE), CTPA.

— Sudden severe "tearing" chest/back pain, pulse/BP differential between arms, widened mediastinum on CXR, neurologic deficits.

— CTPA protocol may miss aortic dissection — request CT angiogram with aortic protocol if suspected. Anticoagulation in undiagnosed dissection is catastrophic.

— Pleuritic pain improved sitting forward, friction rub, diffuse ST elevation with PR depression; tamponade with pulsus paradoxus, JVD, muffled heart sounds.

— Echo distinguishes.

— Orthopnea, PND, bilateral crackles, peripheral edema, elevated BNP (but BNP also elevated in PE), CXR with pulmonary edema/cephalization.

— Key distinction: PE has clear lung fields typically; CHF has wet lungs.

— Beck triad (hypotension, JVD, muffled heart sounds), pulsus paradoxus. Echo diagnostic.

— Can cause dyspnea and tachycardia; but new AF can be a manifestation of PE — investigate for PE if new AF with hypoxia or pleuritic pain.

— Severely elevated BP, pulmonary edema, often LV dysfunction.

— PE can present with syncope (5–10%); distinguish by associated dyspnea, hypoxia, tachycardia at rest.

— Diagnosis of exclusion. Never label dyspnea as anxiety without ruling out PE in any patient with VTE risk factors — a Step 3 trap.

Acute coronary syndrome (ACS):

Aortic dissection:

Pericarditis/pericardial tamponade:

Heart failure (decompensated):

Cardiac tamponade:

Arrhythmia (new AF with RVR, SVT):

Hypertensive emergency with flash pulmonary edema:

Vasovagal/orthostatic syncope:

Anxiety/panic attack:

Key distinction: Clear lungs + hypoxia + tachycardia + risk factor = PE until proven otherwise. Wet lungs point to CHF; consolidation points to pneumonia; absent breath sounds with deviation point to pneumothorax.

Board pearl: A patient with new-onset AF and unexplained hypoxia — order CTPA. New AF is an underrecognized PE presentation.

Key Differentials — Pulmonary and Other-Category Causes

— Productive cough, fever, focal consolidation on CXR, leukocytosis, procalcitonin elevation.

— Overlap: pulmonary infarction from PE can mimic pneumonia (pleuritic pain, fever, infiltrate). Hampton hump suggests infarction.

— When uncertain, CTPA evaluates both.

— Sudden pleuritic pain, dyspnea, decreased breath sounds, hyperresonance, tracheal deviation (tension).

— CXR diagnostic — order before CTPA if exam suggests.

— Dullness, decreased breath sounds, decreased fremitus. Can be parapneumonic, malignant, or from PE-associated infarction.

— Wheezing, prolonged expiration, prior history. However: PE occurs in up to 25% of COPD exacerbations — maintain suspicion if no clear trigger.

— Diffuse bilateral infiltrates, hypoxia, elevated BNP (cardiogenic).

— PE is a noncardiogenic cause of hypoxia but lungs are usually clear.

— Urticaria, angioedema, hypotension, bronchospasm after exposure. Tryptase elevated.

— Fever, source of infection, lactate elevation, distributive shock pattern (warm extremities, low SVR) vs PE's obstructive shock (cold extremities, elevated CVP/JVD, RV dilation).

— Reproducible with palpation, no hypoxia, no tachycardia, normal vitals.

— Burning, related to meals/position, response to PPI or antacid.

— Group 1 (PAH), Group 2 (left heart), Group 3 (lung disease), Group 5. Chronic dyspnea, RV failure signs. Distinguish from acute PE by chronicity and absence of acute clot.

— Triad of hypoxia, neurologic dysfunction, petechial rash 24–72 hours after long-bone fracture or orthopedic surgery.

— Peripartum sudden cardiovascular collapse, DIC, hypoxia. Clinical diagnosis.

Pneumonia:

Pneumothorax:

Pleural effusion:

Acute exacerbation of COPD or asthma:

Pulmonary edema (cardiogenic and noncardiogenic/ARDS):

Anaphylaxis:

Sepsis:

Musculoskeletal chest pain/costochondritis:

GERD/esophageal spasm:

Pulmonary hypertension (non-CTEPH):

Fat embolism syndrome:

Amniotic fluid embolism:

Step 3 management: In a COPD patient with exacerbation NOT responding to bronchodilators/steroids, consider CTPA — concomitant PE changes therapy entirely.

Board pearl: Hemoptysis + pleuritic pain has a wide differential — PE infarction, pneumonia, TB, malignancy, vasculitis (GPA), bronchiectasis. Risk factors and chronicity sort them out.

Secondary Prevention and Long-Term Anticoagulation

— Provoked by transient major risk factor (surgery <90 days, trauma, hospitalization with immobility): 3 months total, then stop.

— Provoked by transient minor risk factor (OCP use, travel, minor surgery, pregnancy): 3 months, then reassess.

— Unprovoked PE: minimum 3 months, then consider indefinite anticoagulation if bleeding risk acceptable.

— Recurrent unprovoked VTE: indefinite anticoagulation.

— Active cancer-associated VTE: anticoagulation until cancer resolved/cured AND minimum 3 months.

— Antiphospholipid syndrome: indefinite warfarin (INR 2–3) — DOACs inferior in triple-positive APS (TRAPS trial).

— Apixaban 2.5 mg BID or rivaroxaban 10 mg daily — equally effective as full-dose for preventing recurrence with less bleeding (AMPLIFY-EXT, EINSTEIN-CHOICE).

— Indicated for unprovoked PE patients continuing beyond initial treatment phase.

— HERDOO2 (women only): hyperpigmentation/edema/redness, D-dimer ≥250 on anticoagulation, BMI ≥30, age ≥65 — score ≥2 = continue; ≤1 = can consider stopping.

— DASH score and Vienna prediction model for recurrence risk.

— Less effective than DOAC for VTE prevention but reduces recurrence ~30% vs placebo; consider when anticoagulation discontinued but residual risk persists.

— Lifestyle: weight reduction, smoking cessation, regular activity, hydration during travel.

— Compression stockings: NOT routinely recommended to prevent post-thrombotic syndrome (SOX trial neutral); use for symptomatic relief of leg swelling.

— Estrogen-containing contraceptives: discontinue and replace with progestin-only or non-hormonal alternatives.

— Discuss travel prophylaxis (LMWH for long flights in high-risk patients with prior VTE).

Duration of anticoagulation — guided by provoked vs unprovoked status:

Reduced-dose extended-phase therapy (after initial 6 months):

Risk stratification tools for stopping anticoagulation:

Aspirin alternative:

Secondary prevention beyond anticoagulation:

Vaccinations: influenza, pneumococcal, COVID-19 — reduce infection-triggered VTE risk.

Step 3 management: A 45-year-old woman with first unprovoked PE — after 3 months full-dose apixaban, transition to apixaban 2.5 mg BID indefinitely if bleeding risk low. Counsel on estrogen avoidance.

Board pearl: Triple-positive APS = warfarin only. DOACs failed in TRAPS trial.

Follow-Up, Monitoring, and Counseling

— Confirm anticoagulant prescription filled and patient understands dosing.

— Provide written instructions in patient's language; teach-back method to confirm understanding.

— Schedule follow-up within 1–2 weeks of discharge.

— Document bleeding precautions and warning signs.

— Address transportation, pharmacy access, ability to afford medication.

— 2 weeks: assess symptoms, adherence, side effects, address questions.

— 1 month: reassess clinical status, repeat CBC and creatinine.

— 3 months: decision point — continue, change to extended low-dose, or stop. Echocardiogram if persistent dyspnea (screen for CTEPH).

— 6 months: if persistent symptoms, V/Q scan + echo for CTEPH workup.

— Annual: comprehensive review of bleeding risk, recurrence risk, renal/hepatic function.

— DOACs: no routine coagulation monitoring; annual CBC, creatinine, LFTs (more often if changing renal function).

— Warfarin: INR every 4 weeks once stable, more often during initiation or dose change.

— LMWH: anti-Xa monitoring in pregnancy, severe obesity, renal impairment, extremes of weight; otherwise not routine.

— Drug interactions — DOACs interact with strong CYP3A4/P-gp inhibitors/inducers (avoid concurrent rifampin, carbamazepine, phenytoin, St. John's wort, certain antifungals/antibiotics).

— Procedure planning — hold DOACs 24–48 hours before low-risk procedures, 48–72 hours before high-risk; longer in renal impairment.

— Travel — adequate hydration, ambulation, prescription refills.

— Pregnancy planning — transition off DOACs preconception; use LMWH if anticoagulation needed.

— Activity — early ambulation reduces post-thrombotic syndrome; no contact sports while anticoagulated.

— Recurrent dyspnea, chest pain, hemoptysis, leg swelling.

— Major bleeding (hematuria, melena, hematochezia, severe epistaxis, intracranial symptoms).

— Falls with head trauma.

— Refer if persistent dyspnea or deconditioning at 3 months.

— Improves exercise capacity and quality of life in post-PE syndrome.

Discharge planning checklist:

Follow-up cadence:

Monitoring parameters:

Counseling points:

Patient warning signs requiring urgent evaluation:

Pulmonary rehab:

CCS pearl: Always order follow-up appointment as a discrete CCS order — Step 3 grades transitions of care, not just acute management.

Board pearl: Persistent dyspnea at 3 months post-PE → echo + V/Q scan for CTEPH. Don't dismiss as deconditioning.

Ethical, Legal, and Patient Safety Considerations

— High-risk procedure with ~2–3% intracranial hemorrhage risk; in unstable patients, two-physician emergency consent or surrogate consent acceptable when patient lacks capacity.

— Document discussion of alternatives (catheter-directed therapy, surgical embolectomy, anticoagulation alone) and contraindications reviewed.

— Choice of DOAC vs warfarin: consider patient preference, cost (warfarin cheaper, requires monitoring), adherence likelihood, food/drug interactions.

— Duration of anticoagulation in unprovoked PE: explicit risk-benefit conversation about lifelong therapy and bleeding.

— Outpatient management eligibility: ensure patient understands risks of home management and warning signs.

— Medication reconciliation at discharge is high-risk; anticoagulants are among the most common medications in adverse drug events.

— Ensure patient receives a scheduled follow-up before discharge, not a "call to schedule" instruction — a Step 3 favorite quality measure.

— Use standardized handoff (e.g., I-PASS) between inpatient and outpatient providers.

— Confirm anticoagulant filled at pharmacy — DOAC cost can be prohibitive without insurance/manufacturer assistance.

— VTE is a CMS hospital-acquired condition when not present on admission and not properly prophylaxed — affects reimbursement.

— DVT/PE prophylaxis assessment is a core quality measure on every hospital admission.

— Maternal mortality from PE — reportable in many jurisdictions, contributes to maternal mortality review committees.

— Sentinel events — hospital-acquired PE with death triggers root-cause analysis.

— Patients refusing anticoagulation must be assessed for capacity: understanding of diagnosis, risks of nontreatment (mortality, recurrent PE), alternatives, and ability to reason. Document all four elements.

— Black patients have higher VTE incidence and mortality; ensure equitable access to advanced therapies (CDT, PERT).

— Language access — provide interpreted consent and discharge instructions.

Informed consent for thrombolysis:

Shared decision-making at key junctures:

Patient safety — transitions of care:

Quality measures and reporting:

Mandatory reporting:

Capacity assessment for AMA refusal:

Disparities awareness:

Step 3 management: A patient on warfarin presents with INR 8 and no bleeding — hold warfarin, oral vitamin K 2.5 mg, recheck INR daily. No need for hospitalization or PCC unless bleeding. Counseling on dietary vitamin K and adherence is mandatory.

Board pearl: Hospital-acquired PE without documented prophylaxis assessment is a never event with reimbursement implications — Step 3 tests this systems concept.

High-Yield Associations and Rapid-Fire Facts

— Saddle embolus: at bifurcation of main pulmonary artery.

— Dead space ventilation increases (ventilated but not perfused alveoli).

— V/Q mismatch from reflexive bronchoconstriction and surfactant loss.

— RV is thin-walled, poorly tolerates acute afterload — fails quickly.

— Factor V Leiden — most common inherited thrombophilia (~5% of Caucasians); activated protein C resistance.

— Prothrombin G20210A — second most common.

— Antithrombin deficiency — heparin resistance (heparin works via antithrombin).

— Protein C deficiency + warfarin → warfarin-induced skin necrosis.

— Antiphospholipid syndrome — arterial + venous thrombosis, recurrent fetal loss, thrombocytopenia, false-positive RPR; need warfarin.

— Trousseau syndrome — migratory superficial thrombophlebitis with adenocarcinoma (pancreas classic).

— Nephrotic syndrome — loss of antithrombin in urine; renal vein thrombosis classic.

— OCPs + smoking — synergistic risk.

— HIT — type II is immune (PF4 antibodies), causes thrombosis paradoxically despite low platelets.

— Westermark sign — oligemia.

— Hampton hump — wedge-shaped infarction.

— Fleischner sign — enlarged central PA.

— McConnell sign — RV free wall hypokinesis with apical sparing (echo).

— "D-sign" — septal flattening from RV pressure overload.

— S1Q3T3.

— T-wave inversions V1–V4.

— Sinus tachycardia (most common).

— New RBBB.

— Wells >4 = PE likely.

— sPESI ≥1 = not low risk.

— PESI Class I–II = outpatient candidate.

— Geneva score (alternative to Wells) — purely objective.

— Apixaban/rivaroxaban: no parenteral lead-in.

— Dabigatran/edoxaban: 5–10 day lead-in required.

— Idarucizumab reverses dabigatran.

— Andexanet alfa reverses apixaban/rivaroxaban.

— Protamine reverses UFH; partially reverses LMWH (~60%).

— PEITHO: tenecteplase in intermediate-risk PE — reduced decompensation, increased bleeding/ICH.

— PREPIC-2: no benefit of IVC filter added to anticoagulation.

— AMPLIFY-EXT: reduced-dose apixaban for extended therapy.

— HOKUSAI-VTE Cancer/CARAVAGGIO: DOACs non-inferior to LMWH in cancer-associated VTE.

Anatomy/physiology:

Classic associations:

Imaging buzzwords:

ECG buzzwords:

Score thresholds:

Pharmacology pearls:

Trials to remember:

Board pearl: PE in a patient with migratory thrombophlebitis = Trousseau syndrome → occult adenocarcinoma, classically pancreatic. Initiate cancer workup.

Board Question Stem Patterns

— 28-year-old on OCPs, recent transcontinental flight, sudden pleuritic chest pain and dyspnea, HR 118, SpO₂ 94%, clear lungs.

— Best next step: CTPA (Wells likely >4 due to tachycardia + PE most likely).

— Trap: ordering D-dimer first → wrong; high pretest probability.

— Postoperative day 3, sudden hypotension, BP 78/40, HR 130, JVD, clear lungs, echo with RV dilation and McConnell sign.

— Best next step: systemic thrombolysis (alteplase 100 mg IV over 2 hours) — bedside echo + clinical picture suffices when too unstable for CTPA.

— Day 7 of UFH after orthopedic surgery; platelets fell from 250 → 110; new DVT on duplex.

— Best next step: stop ALL heparin (including flushes), start argatroban, send HIT antibody/SRA. NO platelet transfusion.

— 32-year-old, 28 weeks pregnant, unilateral leg swelling and dyspnea.

— Best next step: lower extremity ultrasound first; if negative and PE still suspected, V/Q scan or CTPA. Treat with LMWH (not warfarin, not DOAC).

— Patient 8 months after PE with progressive dyspnea on exertion, RV strain on echo.

— Best next step: V/Q scan to screen for CTEPH; if positive, refer for right heart catheterization and pulmonary thromboendarterectomy evaluation.

— Stable PE patient, sPESI = 0, normal troponin, no RV strain, lives 10 min from hospital with family.

— Best next step: discharge on apixaban with 24–72 hour follow-up.

— Patient finishing 3 months of anticoagulation after unprovoked PE.

— Best next step: continue anticoagulation indefinitely (or reduced-dose apixaban/rivaroxaban) if bleeding risk acceptable.

— Contrast: provoked by recent surgery → stop at 3 months.

— Patient with metastatic lung cancer develops PE.

— Best next step: apixaban, rivaroxaban, edoxaban, OR LMWH; avoid DOAC if GI/GU luminal cancer.

— Recurrent VTE + recurrent miscarriages + thrombocytopenia.

— Best next step: lupus anticoagulant + anti–β2-GP I + anticardiolipin × 2 (12 weeks apart); treat with warfarin (INR 2–3), NOT a DOAC.

Stem pattern 1 — The classic young woman:

Stem pattern 2 — The unstable patient:

Stem pattern 3 — The HIT patient:

Stem pattern 4 — The pregnant patient:

Stem pattern 5 — The chronic dyspnea after PE:

Stem pattern 6 — Outpatient eligibility:

Stem pattern 7 — Duration of therapy:

Stem pattern 8 — Cancer-associated VTE:

Stem pattern 9 — APS:

Board pearl: When you see "started on heparin 5 days ago, platelets dropped" — HIT is the answer, argatroban is the drug, no platelet transfusion.

One-Line Recap

Pulmonary embolism management is risk-stratification-driven: confirm with CTPA (or V/Q scan), classify by hemodynamic stability + PESI/sPESI + RV function + biomarkers, and match therapy intensity — outpatient DOAC for low-risk, inpatient anticoagulation for intermediate, thrombolysis or catheter-directed therapy for high-risk — while individualizing duration based on whether the PE was provoked, unprovoked, or cancer/APS-associated.

— Wells score → if PE likely (>4): CTPA. If unlikely (≤4): age-adjusted D-dimer first, then CTPA if positive.

— High pretest probability: skip D-dimer, go straight to CTPA, consider empiric anticoagulation.

— Pregnancy: lower extremity ultrasound first, then V/Q scan or CTPA.

— Hemodynamics (BP, perfusion) + PESI/sPESI score + RV function (echo/CT) and biomarkers (troponin, BNP).

— High-risk = thrombolysis. Intermediate-high = monitor in ICU, rescue lytic if deterioration. Low-risk = consider outpatient.

— First-line: apixaban or rivaroxaban (no lead-in) — preferred in most patients.

— Pregnancy: LMWH only. APS (triple-positive): warfarin only. Severe renal failure: warfarin or UFH.

— Duration: 3 months (provoked) vs indefinite reduced-dose (unprovoked/recurrent) vs while cancer active.

— HIT on day 5–14 of heparin → argatroban, no platelet transfusion.

— Persistent dyspnea at 3–6 months → screen for CTEPH with V/Q scan.

— Unprovoked PE in young patient or migratory thrombophlebitis → consider thrombophilia or occult malignancy workup.

Diagnosis cascade:

Risk stratification triad:

Anticoagulation algorithm:

Don't miss:

Board pearl: CTPA confirms, PESI/sPESI prognosticates, hemodynamics dictate intensity, and provocation status sets duration — master these four axes and PE on Step 3 is a controlled disease.