Deep vein thrombosis and pulmonary embolism management in ICU · ICU Topics

Cinematic ICU scene of a CT pulmonary angiogram on the screen showing a saddle pulmonary embolism, a thrombolysis infusion running, an echocardiogram showing a dilated right ventricle, clinical-blue lighting, no faces, no text — FigureThe venous thromboembolism — stratify the PE by the risk. The massive (the shock) → the thrombolysis or the embolectomy; the submassive (the RV dysfunction, the normotensive) → the anticoagulation and the monitor; the low-risk → the anticoagulation and the early discharge.

Massive vs submassive vs low-risk PE

Feature	Massive (high-risk)	Submassive (intermediate-risk)	Low-risk
Haemodynamics	SBP <90 or shock	Normotensive	Normotensive
RV dysfunction (echo)	Present	Present	Absent
Cardiac biomarkers	Elevated	Elevated	Normal
Mortality	30-60%	5-15%	<3%
Initial treatment	Thrombolysis OR embolectomy	Anticoagulation + MONITOR	Anticoagulation
Rescue thrombolysis	Already given upfront	If deteriorates	Not needed
ICU admission	Yes	Yes (close monitoring)	No (ward or early discharge)
Risk stratification	Clinical (shock)	sPESI + echo + biomarkers	sPESI = 0

[1]

Acute management of massive PE

Assess & resuscitate — ABC. Oxygen, ventilatory support if needed. Avoid excessive fluid (>500 mL bolus worsens RV). Vasopressors (noradrenaline) for shock
Confirm diagnosis — CT pulmonary angiogram (if not delaying treatment). If unstable and high clinical suspicion → may treat empirically (echo: RV strain + DVT)
Anticoagulation — therapeutic LMWH or IV unfractionated heparin (UFH preferred if may need procedures/thrombolysis)
Thrombolysis — alteplase 100 mg over 2h (or 50 mg bolus if deteriorating). Indicated for massive PE. Reversal: aprotinin, cryoprecipitate, TXA if bleeding
If thrombolysis contraindicated/failed — catheter-directed thrombolysis, percutaneous embolectomy, or surgical embolectomy
Consider IVC filter — if anticoagulation contraindicated and recurrent PE
Escalate to ECMO — if refractory shock/collapse. VA-ECMO supports RV and perfusion while clot lyses

[1] [1]

SAQ — Massive PE with systemic thrombolysis

10 minutes · 10 marks

A 58-year-old man, three weeks post right total hip replacement, presents with sudden-onset pleuritic chest pain and dyspnoea. On arrival he is diaphoretic and confused: GCS 14, SBP 76 mmHg, HR 132/min, RR 32/min, SpO2 88% on 15 L via non-rebreather. JVP is elevated; lung fields are clear. ECG shows sinus tachycardia with an S1Q3T3 pattern and T-wave inversion across V1 to V4. Bedside echocardiography demonstrates a dilated right ventricle (RV/LV ratio 1.2), the McConnell sign, septal flattening in systole, TAPSE 12 mm, and a plethoric IVC. CTPA confirms a saddle pulmonary embolus.

[1]

SAQ — Submassive PE risk stratification and the thrombolysis decision

10 minutes · 10 marks

A 67-year-old woman with metastatic breast cancer on weekly paclitaxel presents with two days of progressive dyspnoea and right-sided pleuritic chest pain. Vital signs: BP 112/68 mmHg, HR 108/min, RR 24/min, SpO2 94% on room air. She is not hypotensive. ECG shows sinus tachycardia only. CTPA demonstrates bilateral segmental pulmonary emboli with an RV/LV ratio of 1.1. Troponin T is 0.06 ng/mL (normal below 0.04); NT-proBNP is 1200 pg/mL (elevated). Bedside echocardiography shows mild RV dilatation, septal flattening in systole, and TAPSE 14 mm.

[1]

Clinical pearls

High-yield VTE management points for CICM/FFICM exam

Severity stratification determines treatment. Massive PE (shock/SBP <90) → thrombolysis or embolectomy. Submassive PE (RV dysfunction + biomarkers, normotensive) → anticoagulation + close monitoring, rescue thrombolysis if deteriorates. Low-risk PE → anticoagulation + early discharge. This is THE key management decision.[2] }
Massive PE: give thrombolysis FIRST, then anticoagulation. Alteplase 100 mg over 2 hours. If cardiac arrest: 50 mg bolus. Stop heparin during infusion (controversial — some continue). Resume heparin when aPTT <1.5x control. Do NOT delay thrombolysis for confirmatory CTPA if high suspicion and unstable — treat empirically.[2] }
Submassive PE: PEITHO trial. Tenecteplase vs placebo in normotensive PE with RV dysfunction + troponin. Result: REDUCED death/hemodynamic decompensation (2.6% vs 5.6%) but INCREASED major bleeding (11.5% vs 2.4%) and haemorrhagic stroke (2.4% vs 0.2%). NET: no clear mortality benefit. Current practice: anticoagulation + close monitoring. Thrombolysis ONLY if clinical deterioration (rescue thrombolysis).[1] }
RV dysfunction = the danger sign. Echo: RV dilatation, RV hypokinesis, McConnell's sign (free wall akinesis with apical sparing), D-shaped LV (septal flattening), tricuspid regurgitation, pulmonary hypertension. Biomarkers: troponin (myocardial injury), BNP/NT-proBNP (RV strain). Presence of EITHER = higher risk. BOTH present = highest risk.[2] }
Anticoagulation choice: STABLE patients → DOAC (rivaroxaban 15 mg BD × 3 weeks, then 20 mg OD; or apixaban 10 mg BD × 7 days, then 5 mg BD). UNSTABLE or renal failure → LMWH (enoxaparin 1 mg/kg BD) or IV UFH. CANCER → LMWH preferred over DOAC (CATCH, SELECT-D trials). ANTIPHOSPHOLIPID SYNDROME → warfarin (INR 2-3). PREGNANCY → LMWH (avoid DOACs, avoid warfarin).[1] }
Heparin-induced thrombocytopenia (HIT). Platelets fall 5-10 days after starting heparin (or rapidly if previously exposed). Type 2 HIT: IgG against PF4-heparin → platelet activation → THROMBOSIS (paradoxical). Diagnosis: 4Ts score (Thrombocytopenia, Timing, Thrombosis, oTher cause). Confirm: anti-PF4 antibody (ELISA), serotonin release assay (SRA). Treatment: STOP ALL heparin (including flushes, LMWH). Start argatroban or bivalirudin (direct thrombin inhibitors). Warfarin only when platelets recovered (overlap with non-heparin anticoagulant).[1] }
Catheter-directed thrombolysis (CDT). Ultrasound-assisted (EKOS) or standard catheter delivers low-dose alteplase directly into clot. ADVANTAGE: lower systemic dose → less bleeding than systemic thrombolysis. Evidence: ULTIMA (2014), SEATTLE II (2015) — reduced RV/LV ratio, low major bleeding. LIMITATION: requires interventional radiology, not available everywhere. Indication: submassive PE with RV dysfunction, high bleeding risk. Controversial for massive PE.[5] }
Surgical embolectomy. Indications: massive PE with thrombolysis contraindicated or failed, large free-floating right-heart thrombus, paradoxical embolism (PFO with embolic stroke). Requires cardiothoracic surgery + cardiopulmonary bypass. Mortality: 20-40% (high, but for patients who would otherwise die).[2] }
Phlegmasia cerulea dolens. Massive iliofemoral DVT → entire limb blue, swollen, painful → arterial compromise (pulseless) → gangrene → amputation. Emergency: catheter-directed thrombolysis or surgical thrombectomy. Phlegmasia alba dolens: white limb (earlier stage, pulseless but not yet blue). Pre-phlegmasia: massive swelling without arterial compromise.[6] }
Duration of anticoagulation: PROVOKED (surgery, immobility) → 3 months. PROVOKED (non-surgical — cancer, oestrogen) → 3 months, reassess. UNPROVOKED → extended (lifelong) unless bleeding risk. CANCER → extended while cancer active (LMWH or DOAC). ANTIPHOSPHOLIPID SYNDROME → lifelong warfarin. SECOND unprovoked → lifelong.[1] }
IVC filters. Indications: (1) Anticoagulation CONTRAINDICATED (active bleeding) + acute proximal DVT. (2) Recurrent PE despite adequate anticoagulation. NOT for routine prophylaxis. RETRIEVABLE filters preferred (remove within 3-6 months when anticoagulation can resume). Complications: migration, IVC thrombosis, penetration, retrieval failure.[3] }
PE in pregnancy. Diagnosis: bilateral leg Doppler first (if positive, treat without CTPA — avoid radiation). If Doppler negative and PE suspected: V/Q scan (lower radiation than CTPA, good sensitivity in pregnancy). Treatment: LMWH throughout pregnancy (enoxaparin 1 mg/kg BD). AVOID warfarin (teratogenic, fetal bleeding). AVOID DOACs (limited data). Postpartum: warfarin OK, breastfeed. Thrombolysis if massive PE (alteplase does not cross placenta significantly).[6] }
Right-heart thrombus in-transit. Free-floating clot in right atrium/ventricle → high risk of embolisation. Management: controversial. Options: anticoagulation, thrombolysis, surgical embolectomy. If PFO present → risk of paradoxical embolism (stroke). Most centres: thrombolysis or embolectomy if unstable.[2] }
ECMO for massive PE. VA-ECMO supports circulation (RV failure, low output) and oxygenation while clot lyses. Indication: refractory shock/cardiac arrest from massive PE. Bridge to embolectomy or thrombolysis. Requires specialist centre. Outcomes: reasonable if initiated before irreversible organ damage.[2] }

Red flags

Prognosis

PEITHO trial (Meyer 2014, NEJM)

RCT: 1006 patients with normotensive PE + RV dysfunction + troponin positive. Tenecteplase (weight-based single bolus) vs placebo, all received anticoagulation.

Primary outcome (death/hemodynamic decompensation at 7 days): tenecteplase 2.6% vs placebo 5.6% (RR 0.44, NNT 33)
Major bleeding: tenecteplase 11.5% vs placebo 2.4% (NNH 11)
Haemorrhagic stroke: tenecteplase 2.4% vs placebo 0.2% (NNH 45)
CONCLUSION: Routine thrombolysis in submassive PE reduces hemodynamic decompensation but at significant bleeding cost. Current practice: anticoagulation + monitor; reserve thrombolysis for clinical deterioration.

[1]

Diagnosis

Clinical probability assessment

Wells score: PE vs DVT

	Wells score for PE	Wells score for DVT
Clinical signs/symptoms of DVT	3.0	3.0
PE more likely than alternative diagnosis	3.0	—
Heart rate >100	1.5	—
Immobilisation ≥3 days or surgery in past 4 weeks	1.5	1.0
Previous DVT/PE	1.5	1.0
Haemoptysis	1.0	—
Malignancy (on treatment, palliative, or past 6 mo)	1.0	1.0
Tenderness along deep veins / ≥3 cm calf swelling	—	1.0 each
Pitting oedema (symptomatic leg)	—	1.0
Collateral superficial veins	—	1.0
Alternative diagnosis at least as likely	—	−2.0
Interpretation (3-tier)	'PE likely' ≥4; 'PE unlikely' <4 (dichotomised)	High ≥3; Moderate 1-2; Low <1
Interpretation (2-tier)	PE likely ≥4 / PE unlikely <4	DVT likely ≥2 / unlikely <2

[1]

The dichotomised (2-tier) Wells score is preferred in modern algorithms because it simplifies the diagnostic pathway — 'PE unlikely' permits a D-dimer gate, while 'PE likely' mandates imaging regardless of D-dimer. The Wells score performs modestly (inter-observer variability, LR+ ≈5 for 'PE likely'), which is why it is never used alone — it gates D-dimer and imaging.[8] }[9] }

Diagnostic algorithm for suspected PE (Christopher / YEARS pathway)

Apply Wells score (2-tier) — stratify into 'PE unlikely' (<4) or 'PE likely' (≥4). This is the entry point for every stable suspected PE.[9] }
If 'PE unlikely' → check D-dimer — high-sensitivity ELISA/turbidimetric assay only. D-dimer NEGATIVE (<500 µg/L, or age-adjusted if >50 yr) → PE excluded, no imaging, discharge or seek alternative diagnosis.[16] } D-dimer POSITIVE → proceed to CTPA.
If 'PE likely' → D-dimer is unhelpful (specificity too low) → go straight to CTPA.
CTPA — first-line imaging in the haemodynamically stable patient. Shows filling defect in pulmonary artery, RV/LV ratio, and concomitant DVT.
If CTPA contraindicated (renal failure, contrast allergy, pregnancy) → lower-limb compression venous ultrasound (if positive → treat as PE); if negative, V/Q scan or V/Q SPECT.
If unstable/unable to transfer to CT → bedside echo (RV strain), bedside venous ultrasound. If high pre-test probability + RV strain → treat empirically as PE (do not delay reperfusion).[2] }
YEARS algorithm (alternative) — assess 3 Wells items (clinical signs DVT, PE most likely, haemoptysis). If none present AND D-dimer <1000 → PE excluded; if D-dimer <500 → excluded regardless. Fewer CTPAs vs standard pathway.[21] }

D-dimer

D-dimer strategies in suspected PE

Strategy	Rule	Use / evidence
Standard cutoff	<500 µg/L (FEU) excludes PE	Specificity poor (~50%), falls with age. Use only with 'PE unlikely' pre-test probability
PERC rule	If 'PE unlikely' + ALL 8 PERC criteria negative + age <50 → no D-dimer, no imaging	Kline 2008: safely reduces testing in low-risk young patients. Miss rate <1.5%. Must be <50 yr, no hormones, no haemoptysis, no surgery/trauma, no prior VTE, no unilateral leg swelling, HR <100, no oxygen requirement.[11] }
Age-adjusted D-dimer	Cutoff = age × 10 µg/L (if >50 yr)	ADJUST-PE: in >50 yr 'PE unlikely' patients, tripled the proportion in whom PE could be excluded (from 6.4% to 11.9%) with <1% 3-month VTE risk.[16] }
YEARS algorithm	3-item Wells + tiered D-dimer (<1000 if 0 items, <500 if any)	YEARS study: safely reduced CTPA use ~17% vs conventional algorithm; low failure rate.[21] }
Pregnancy-adjusted	YEARS / adapted in pregnancy; CTPA if D-dimer positive	Avoid radiation; bilateral leg Doppler first. D-dimer physiologically rises in pregnancy so use as 'rule-out' gate only with low/moderate probability

Imaging

CTPA vs V/Q scan in suspected PE

Feature	CT pulmonary angiography (CTPA)	Ventilation/perfusion (V/Q) scan
Sensitivity/specificity	Sens ~83%, Spec ~96% (PIOPED II); misses subsegmental clots	Sens high (with SPECT); V/Q SPECT spec ~97%
Pros	Fast, widely available, gives alternative dx (aortic dissection, pneumonia, effusion), RV/LV ratio, concomitant DVT	No contrast nephropathy, lower radiation dose, preferred in pregnancy/renal failure/contrast allergy
Cons	Contrast nephropathy, radiation, overdiagnosis of subsegmental PE (incidentalomas)	Non-diagnostic 'intermediate' result in ~25-50% (especially with COPD/prior cardiopulmonary disease), no alternative diagnosis
PIOPED data	PPV high for segmental/proximal; low for subsegmental	High-probability scan: PPV ~88% (sufficient to treat); normal scan: PE excluded; 'intermediate' → further imaging.[7] }
Best use	Default first-line in stable patient	Pregnancy, renal failure, contrast allergy, follow-up of known PE
Reporting	Filling defect in PA; RV/LV ratio >0.9 suggests RV strain	'High probability', 'intermediate', 'low', 'normal' (modified Prospective Investigative Study interpretation)

Risk stratification (severity)

Educational diagram of PE risk stratification into high-risk (shock), intermediate-risk (RV dysfunction, normotensive), and low-risk strata with corresponding reperfusion vs anticoagulation pathways — FigurePE risk strata drive therapy — shock needs reperfusion; intermediate needs monitoring and rescue readiness; low-risk needs anticoagulation and early mobility.

PE severity drives treatment intensity. The 2020 ESC algorithm stratifies by early mortality risk (in-hospital / 30-day):[2] }

High-risk (massive) — clinical: shock or sustained hypotension (SBP <90 for >15 min, or needing catecholamines, or drop ≥40 mmHg). ~5% of PEs. Mortality >15%. Reperfusion mandatory (thrombolysis, surgical or percutaneous embolectomy, or catheter-directed treatment).
Intermediate-risk (submassive) — normotensive but RV dysfunction (imaging) and/or myocardial injury (biomarkers). Subdivided:
- Intermediate-high: RV dysfunction AND biomarker elevation (both). ~20%. Monitor closely, consider rescue reperfusion.
- Intermediate-low: RV dysfunction OR biomarker elevation (one only). ~30%. Anticoagulate, monitor.
Low-risk — sPESI = 0, no RV dysfunction, normal biomarkers. ~40-50%. Anticoagulate, possible early discharge / outpatient. [1]

sPESI / PESI

The full PESI score predicts 30-day mortality; the simplified PESI (sPESI) uses 6 equally weighted items (see SeverityGauge above).[10] } sPESI = 0 identifies low-risk patients suitable for outpatient/early-discharge management — provided they are also clinically stable, with good social support, no significant comorbidity, and (per ESC) no significant RV dysfunction or biomarker elevation. The Bova score and FAST score further risk-stratify intermediate-risk PE for haemodynamic deterioration.

Right ventricular strain

RV strain: imaging and biomarker markers

Marker	Finding	Significance
Echocardiography — RV dilatation	RV/LV basal diameter ratio >0.6 (apical 4-chamber), or RV end-diastolic area > LV	Acute pressure overload; present in ~40% of normotensive PE
McConnell's sign	RV free-wall hypokinesis/akinesis with apical sparing (hyperdynamic apex)	Specific (~94%) but modestly sensitive (~77%) for PE; reflects differential wall stress
TAPSE (tricuspid annular plane systolic excursion)	<16 mm indicates RV systolic dysfunction	Per Rudski 2010 echo guidelines; independent predictor of PE mortality.[12] }
Septal flattening / D-shaped LV	Paradoxical septal motion in systole (pressure overload) and/or diastole (volume overload)	Indicates RV pressure >~40 mmHg
Tricuspid regurgitant jet velocity	>2.6 m/s (≈ >2.7-2.8) suggests pulmonary HTN	Reflects elevated pulmonary artery pressure
RV/LV ratio on CTPA	>0.9 (4-chamber reformats)	CT equivalent of echo RV dilatation; prognostic
Troponin (I/T)	Elevated = myocardial injury	RV microinfarction; risk of death/haemodynamic collapse
BNP / NT-proBNP	Elevated = RV wall stress/strain	Surrogate of RV dysfunction; combined with troponin identifies highest-risk patients
Lactate	Elevated = tissue hypoperfusion	Marker of haemodynamic compromise; prognostic in intermediate-risk PE

The presence of both RV dysfunction (echo) and biomarker elevation (troponin/BNP) defines intermediate-high-risk PE — the group that warrants ICU admission for close haemodynamic monitoring and for whom a rescue thrombolysis strategy is reserved (treat with anticoagulation; give systemic lysis only if clinical deterioration).[1] } Either marker alone = intermediate-low risk; neither = low risk.

Thrombolysis

Alteplase for massive PE

Standard regimen: alteplase 100 mg IV over 2 hours (approved FDA regimen for massive PE). In cardiac arrest or peri-arrest, a 50 mg IV bolus is widely used. Stop UFH during infusion in many protocols (controversial — some centres continue without bolus). Resume heparin (no bolus) when aPTT <1.5× control (typically at end of infusion). Reversal of life-threatening bleeding: cryoprecipitate (fibrinogen), TXA / aminocaproic acid, and if available aprotinin; activate massive transfusion protocol. [1]

Contraindications to systemic thrombolysis

Absolute vs relative contraindications to alteplase

Absolute	Relative (weigh benefit in massive PE)
Haemorrhagic stroke or stroke of unknown origin at any time	TIA in preceding 6 months
Ischaemic stroke in preceding 6 months	Central nervous system neoplasm
CNS neoplasm	Recent major surgery (<3 weeks)
Major trauma/surgery/head injury in preceding 3 weeks	Recent internal bleeding (<4 weeks) — non-CNS
Active bleeding / bleeding diathesis	Non-compressible vascular puncture
Structural cerebral vascular lesion	Pregnancy / early postpartum
Recent brain/spinal surgery	Age >75 yr
Active intracranial / spinal lesion	Uncontrolled HTN (SBP >180)
Recent (≤2 wk) intracranial/spinal surgery	Anticoagulant use (INR elevated)
Thrombocytopenia (<100 × 10⁹/L)	Peptic ulcer, severe liver disease, infective endocarditis

[1]

In massive PE, the only true absolute contraindication is active life-threatening bleeding / recent haemorrhagic stroke — the high mortality of untreated massive PE justifies lysis even with relative contraindications. Where lysis is contraindicated, surgical embolectomy or percutaneous catheter-directed thrombolysis/embolectomy are the alternatives.[2] }

Catheter-directed thrombolysis (CDT)

Low-dose alteplase (typically 1 mg/hour per catheter, total 20-24 mg over 12-24 h) infused directly into the pulmonary artery via ultrasound-assisted catheter (EKOS) or standard multi-side-hole catheter. Advantages: fraction of systemic alteplase dose → markedly lower major bleeding; rapid reduction in RV/LV ratio and pulmonary artery pressure. [1]

ULTIMA trial (Kucher 2014, Circulation): ultrasound-assisted CDT vs systemic heparin in intermediate-risk PE (RV/LV ≥1.0). CDT reduced RV/LV ratio at 24 h significantly more than heparin (0.99 ± 0.16 vs 1.08 ± 0.23); no major bleeding. Small but pivotal trial establishing efficacy in submassive PE.[17] }
SEATTLE II (Piazza 2015, JACC): 150 patients with massive or submassive PE. US-facilitated CDT reduced RV/LV ratio by 0.42 and PA pressure by 7 mmHg; major bleeding 10% but zero intracranial haemorrhage.[18] }
Indication: submassive (intermediate-risk) PE with RV dysfunction where systemic lysis is high-risk/contraindicated, and in centres with interventional radiology. AHA guidelines support CDT for selected patients with intermediate-high-risk PE failing anticoagulation.

Catheter-directed therapy for DVT — ATTRACT

Phlegmasia / iliofemoral DVT — to lyse or not

Confirm iliofemoral (proximal) DVT with ultrasound ± venography; assess limb viability (pulse, capillary refill, sensation).
Phlegmasia cerulea dolens (blue, painful, swollen limb ± pulseless) → emergency: catheter-directed thrombolysis ± pharmacomechanical thrombolysis (rheolytic/PMT), or surgical thrombectomy if lysis contraindicated.
Stable iliofemoral DVT (no limb threat) — ATTRACT trial (Vedantham 2017): CDT + PMT vs anticoagulation alone reduced post-thrombotic syndrome (PTS) severity (especially severe PTS) but did NOT reduce overall PTS rate, at the cost of more bleeding. Practice: selective use in severe proximal DVT with high PTS risk; not routine.[22] }
May-Thurner syndrome (left common iliac vein compressed by right common iliac artery) → consider venoplasty + stenting after thrombolysis.
Post-procedure: resume anticoagulation; surveillance ultrasound; assess for underlying thrombophilia/malignancy.

Anticoagulation

DOAC vs warfarin vs LMWH for VTE

Agent	Acute dose	Maintenance	Renal / special	Trial evidence
Rivaroxaban (Xa)	15 mg BD × 21 days	20 mg OD	Avoid CrCl <15; caution <30	EINSTEIN-DVT/PE — non-inferior to warfarin, less major bleeding. Single-drug (no parenteral lead-in).[14] }
Apixaban (Xa)	10 mg BD × 7 days	5 mg BD	Avoid CrCl <15; dose-adjust if ≥80 yr or ≤60 kg or Cr ≥133	AMPLIFY — non-inferior, less bleeding. Single-drug.
Dabigatran (IIa)	Parenteral lead-in 5-10 days (LMWH/UFH) then	150 mg BD	Avoid CrCl <30	RE-COVER — non-inferior to warfarin, less major bleeding; requires heparin lead-in.[13] }
Edoxaban (Xa)	Parenteral lead-in 5-10 days then	60 mg OD (30 mg if CrCl 15-50 or ≤60 kg)	Contraindicated CrCl <15; ineffective in CrCl >95	Hokusai-VTE — non-inferior to warfarin, less clinically relevant bleeding.[15] }
Warfarin (Vit K epoxide reductase)	Overlap parenteral ≥5 days AND until INR 2-3 × 24 h	INR 2-3	Preferred for antiphospholipid syndrome, mechanical valve, severe renal failure	Long-standing standard; DOACs preferred for most others
LMWH (enoxaparin)	1 mg/kg SC BD (or 1.5 mg/kg OD)	Same	Preferred for cancer-associated VTE and pregnancy; avoid CrCl <30 (dose-adjust)	CATCH, SELECT-D, Caravaggio — DOACs non-inferior in cancer too
IV UFH	80 U/kg bolus, 18 U/kg/h infusion (weight-based, aPTT 1.5-2.5×)	—	Preferred in massive PE / pre-thrombolysis (short half-life, reversible), severe renal failure, obesity	—
Fondaparinux	5-10 mg SC OD (weight-based)	—	Avoid CrCl <30; HIT-safe alternative	—

Selection principles: [1]

Stable, otherwise well → rivaroxaban or apixaban (single-drug, oral from day 1, no monitoring).
Massive PE / pre-thrombolysis / unstable / likely procedures → IV UFH (titratable, short half-life, fully reversible with protamine).
Cancer-associated VTE → apixaban, rivaroxaban, or LMWH per current guidance (Caravaggio: apixaban non-inferior to dalteparin; SELECT-D: rivaroxaban reduced recurrence vs LMWH with more non-major bleeding).
Antiphospholipid syndrome (triple-positive) → warfarin (DOACs inferior in APS — TRAPS trial).
Severe renal failure (CrCl <15-30) → IV UFH or warfarin.
Pregnancy / breastfeeding → LMWH throughout; switch to warfarin postpartum (breastfeeding OK).
Extremes of weight → IV UFH (reliable) or LMWH with anti-Xa monitoring. [1]

Duration of anticoagulation

Duration of anticoagulation by VTE provocation

Scenario	Duration
Provoked by major transient risk (surgery, trauma, immobility)	3 months
Provoked by non-surgical transient risk (oestrogen, pregnancy, transient immobility)	3 months
First unprovoked proximal DVT/PE	≥3 months, then reassess bleed vs recurrence risk; extend if low bleeding risk
Second unprovoked VTE	Lifelong
Cancer-associated VTE	Extended while cancer active
Antiphospholipid syndrome	Lifelong warfarin
Distal (calf) DVT, symptomatic	3 months

[1]

Recurrent VTE despite therapeutic anticoagulation → switch LMWH (if on warfarin/DOAC), check adherence/compliance, screen for malignancy and thrombophilia, consider IVC filter. [1]

Inferior vena cava filters

Indications (per SIR and CHEST/ESC guidance)

IVC filter decision pathway

Absolute indication: acute VTE (proximal DVT or PE) with a CONTRAINDICATION to anticoagulation (active bleeding, imminent surgery) — place retrievable filter.[19] }
Absolute indication: recurrent PE despite adequate therapeutic anticoagulation → place filter AND continue/escalate anticoagulation.[1] }
Relative indications (case-by-case): massive PE with residual DVT and high re-embolisation risk; large free-floating proximal DVT; thrombolysis/embolectomy planned; severe cardiopulmonary compromise where a further embolus would be fatal; iliofemoral DVT in pregnancy near delivery.
NOT recommended: routine prophylaxis in trauma/surgery patients who CAN receive anticoagulation (PREPIC2 showed no benefit when added to anticoagulation).[20] }
Use retrievable filters — remove within 3-6 months once anticoagulation can be resumed. Track every filter in a registry to avoid permanent retention.
Complications: filter migration/embolisation, IVC thrombosis (causes filter dysfunction + leg swelling), IVC penetration (through wall → adjacent structures), retrieval failure, access-site thrombosis.

PREPIC trials

PREPIC (1998, NEJM): permanent IVC filter + anticoagulation vs anticoagulation alone → filter reduced recurrent PE (1.1% vs 4.8% at 12 days) but increased DVT recurrence at 2 years (21% vs 12%); no mortality difference. At 8 years PE reduction persisted, DVT excess persisted, no survival benefit.[19] }
PREPIC2 (2015, JAMA): retrievable filter + anticoagulation vs anticoagulation alone in patients with PE + DVT + risk factors → NO reduction in recurrent PE at 3 or 6 months. Filters confer no benefit when patients can receive anticoagulation.[20] }

Subsegmental PE management

Management pathway for ICU VTE: anticoagulation backbone, systemic or catheter-directed thrombolysis for high-risk PE, embolectomy when lysis fails or is contraindicated, and selective IVC filter use — FigureAnticoagulate unless absolutely contraindicated; reperfuse high-risk PE; reserve IVC filters for the anticoagulation-contraindicated exception.

Subsegmental PE (isolated) — management

Confirm isolated subsegmental PE on CTPA (clot in a subsegmental branch, no more proximal clot). Increasingly detected with modern multidetector CT — many are clinically insignificant.
Assess whether symptomatic: presentation with PE symptoms (pleuritic pain, dyspnoea) vs incidental finding on CT performed for another reason (e.g., cancer staging).
Risk-stratify recurrence / proximal DVT: perform bilateral lower-limb compression venous ultrasound — if proximal DVT present, treat as proximal VTE (full-dose, 3+ months).
Decision per CHEST 2016 guidance: with risk factors for recurrence (cancer, previous VTE, hospitalisation, proximal DVT) OR symptomatic → anticoagulate (DOAC, full duration); with no risk factors AND asymptomatic → clinical surveillance (serial imaging/clinical review), anticoagulation may be withheld. Discuss risk-benefit with patient.
Reassess for provoking cause (occult malignancy screen if unprovoked).
Do NOT routinely image follow-up unless recurrent symptoms — residual thrombus is common and does not guide duration.

[1]

The rise in isolated subsegmental PE diagnosis (driven by sensitive multidetector CT) has not been matched by a fall in PE mortality, fuelling concern about overdiagnosis of clinically unimportant clots. The principle: an isolated subsegmental PE in an asymptomatic patient with no provoking risk factor may reasonably be observed rather than anticoagulated — individualise.[3] }

Clinical pearls (extended)

Diagnostic and pharmacological VTE pearls for the exam

Wells score is a gate, not a diagnosis. It is never used alone — it gates the D-dimer step and imaging. 'PE unlikely' (<4) lets D-dimer rule out; 'PE likely' (≥4) mandates CTPA regardless of D-dimer. Inter-observer agreement is modest, so in the ICU where pre-test probability is high, image directly.[8] }[9] }
PERC first, then D-dimer, in the low-risk young. If 'PE unlikely' AND age <50 AND all 8 PERC items negative (no hormone use, no haemoptysis, no surgery/trauma, no prior VTE, no unilateral leg swelling, HR <100, no exogenous oxygen requirement) → no D-dimer, no imaging: miss rate <1.5%. Saves investigation and radiation in the truly low-risk.[11] }
D-dimer is only a rule-OUT test, and only in low pre-test probability. Sensitivity >95% but specificity ~50% (lower in inflammation, malignancy, pregnancy, post-op, elderly). A POSITIVE D-dimer proves nothing — image. A NEGATIVE D-dimer in 'PE likely' is unhelpful; the assay cannot safely exclude in high probability. Do not order D-dimer in a patient you plan to image regardless.[9] }
Use the age-adjusted D-dimer in patients >50. ADJUST-PE: cutoff = age × 10 µg/L (e.g., a 75-yr-old: 750 µg/L) nearly triples the proportion of 'PE-unlikely' patients in whom PE can be safely excluded (6.4% → 11.9%) with <1% 3-month VTE risk. Underused but validated and guideline-endorsed.[16] }
CTPA vs V/Q — pick by the patient, not the habit. CTPA is default first-line (fast, gives alternative diagnosis, RV/LV ratio, concomitant DVT) but causes contrast nephropathy and overdiagnoses subsegmental clots. V/Q (ideally SPECT) is preferred in pregnancy, renal failure, contrast allergy, and for PE follow-up. PIOPED showed a 'high-probability' V/Q is sufficient to treat, and a 'normal' scan excludes — but ~half are 'indeterminate'.[7] }
In the unstable patient, do not delay reperfusion for CTPA. Bedside echo showing RV strain (dilatation, McConnell's sign, septal flattening, low TAPSE) plus a high pre-test probability justifies empirical thrombolysis. Irreversible shock is the enemy of imaging. A confirmatory CTPA can follow if the patient stabilises.[2] }
McConnell's sign: high specificity, watch the mimic. RV free-wall akinesis with a hyperdynamic apex is ~94% specific for PE — but beware Takotsubo (stress) cardiomyopathy, which produces the same apical-sparing pattern. The clinical context (DVT, risk factors, sudden dyspnoea + hypoxia with normal LV) disambiguates.[12] }
TAPSE <16 mm = RV systolic dysfunction and a mortality predictor. Tricuspid annular plane systolic excursion is a quick, reproducible M-mode measure (Rudski 2010 echo guidelines). In PE, low TAPSE reflects pump failure and predicts haemodynamic deterioration — combine with troponin/BNP to identify intermediate-high-risk patients who need ICU monitoring.[12] }
Troponin + BNP together = the highest-risk intermediate group. Either marker alone = intermediate-low risk. Both elevated (RV injury AND wall stress) = intermediate-high risk — the group that PEITHO studied and in whom rescue thrombolysis is held in reserve. Neither marker elevated + sPESI 0 = low risk (discharge candidate).[1] }
Alteplase: 100 mg over 2 h for massive PE, 50 mg bolus in arrest. Hold/stop heparin during infusion in most protocols; resume (no bolus) when aPTT <1.5× control. For submassive PE, PEITHO used tenecteplase (single weight-based bolus) — showed reduced haemodynamic decompensation (2.6% vs 5.6%) but at the cost of more major bleeding (11.5% vs 2.4%) and haemorrhagic stroke (2.4% vs 0.2%). Net: anticoagulate + monitor; lyse only on deterioration.[1] }
Contraindications to lysis are relative in MASSIVE PE. The only near-absolute is recent haemorrhagic stroke / active life-threatening bleeding. Pregnancy, recent surgery, age >75, uncontrolled hypertension are relative — weigh against the 30-60% mortality of untreated massive PE. If lysis truly impossible → surgical or percutaneous embolectomy, or VA-ECMO as a bridge.[2] }
Catheter-directed thrombolysis: same drug, ~1/5 the dose, far less bleeding. ULTIMA (intermediate-risk PE) showed ultrasound-assisted CDT reduced RV/LV ratio more than heparin at 24 h with no major bleeding; SEATTLE II (n=150) cut RV/LV ratio by 0.42 with zero intracranial haemorrhage. Reserve for intermediate-high-risk PE failing anticoagulation or where systemic lysis is high-risk — needs interventional radiology.[17] }[18] }
ATTRACT changed DVT practice: CDT is not routine. Pharmacomechanical CDT reduced SEVERE post-thrombotic syndrome but not overall PTS, with more bleeding. Reserve CDT for phlegmasia cerulea dolens (limb-threatening) and selected severe iliofemoral DVT; do not lyse routine proximal DVT.[22] }
DOAC selection — three families, two strategies. (a) Single-drug oral from day 1: rivaroxaban 15 mg BD ×3 wk → 20 mg OD (EINSTEIN), or apixaban 10 mg BD ×7 d → 5 mg BD (AMPLIFY). (b) Parenteral lead-in then oral: dabigatran (RE-COVER) or edoxaban (Hokusai) require 5-10 days LMWH/UFH first. All four non-inferior to warfarin with less bleeding; choice by renal function, tolerability, and local cost.[13] }[14] }[15] }
Edoxaban and dabigatran: mind the renal limits. Edoxaban is contraindicated if CrCl >95 mL/min (sub-therapeutic, excess recurrence). Dabigatran needs a heparin lead-in. For reliable single-drug oral therapy in the well patient, rivaroxaban or apixaban are simplest. For CrCl <15, fall back to IV UFH or warfarin.[15] }
Warfarin still wins in antiphospholipid syndrome. Triple-positive APS patients given DOACs had more events (TRAPS, RAPS) — use warfarin INR 2-3 (sometimes higher target). Warfarin also for mechanical heart valves, severe renal failure (where DOACs accumulate), and patient preference where monitoring is feasible.[1] }
IVC filters prevent PE only when anticoagulation cannot be given. PREPIC (permanent filters) cut recurrent PE but increased DVT and gave no survival benefit; PREPIC2 (retrievable + anticoagulation) showed NO benefit when added to anticoagulation. Filters are for (1) absolute contraindication to anticoagulation, or (2) recurrent PE despite therapeutic anticoagulation. Use retrievable filters, remove within 3-6 months, and track every one — IVC thrombosis, penetration, and migration are real complications.[19] }[20] }
Subsegmental PE: observe the asymptomatic low-risk, anticoagulate the rest. Isolated subsegmental PE on CTPA in an asymptomatic patient with no cancer/prior VTE/immobility and negative proximal leg ultrasound may be observed (CHEST 2016). Symptomatic or recurrent-risk patients get full-dose anticoagulation. Multidetector CT has inflated detection of clinically trivial clots — mortality has not fallen alongside.[3] }
Heparin resistance — check antithrombin. Patients needing escalating UFH doses without achieving aPTT/anti-Xa target may have antithrombin deficiency (congenital, or acquired in cirrhosis/nephrosis/ECMO). Direct thrombin inhibitors (argatroban, bivalirudin) bypass antithrombin. Also consider elevated factor VIII (acute phase) raising aPTT unreliably — use anti-Xa to monitor.
Cancer-associated VTE: DOACs are now first-line alongside LMWH. Caravaggio (apixaban) and SELECT-D (rivaroxaban) showed non-inferiority to LMWH (dalteparin) with manageable bleeding (SELECT-D: more non-major, particularly GI in GI cancer). LMWH remains preferred in upper-GI/luminal GI cancers with high bleeding risk, in pregnancy, and in platelet <50 settings. Continue anticoagulation while cancer is active.[1] }

Red flags (extended)

Critical and easily-missed VTE red flags (extended)

Massive PE (SBP <90, shock, arrest) → thrombolysis/embolectomy immediately; mortality 30-60%. Do NOT delay for CTPA if high pre-test probability — treat empirically.[2] }
Intermediate-high-risk PE (RV dysfunction + troponin/BNP) → ICU monitoring; rescue thrombolysis if haemodynamic deterioration. Anticoagulate first-line.[1] }
McConnell's sign + sudden dyspnoea → highly specific for PE; image or treat empirically if unstable.[12] }
Free-floating right-heart thrombus (in-transit) → high embolisation risk; thrombolysis or embolectomy, especially if PFO (paradoxical embolism → stroke).[2] }
Phlegmasia cerulea dolens (blue, pulseless limb) → limb-threatening; emergency catheter-directed thrombolysis/thrombectomy.[6] }
HIT (platelets fall 5-10 d after heparin) → stop ALL heparin including flushes and LMWH; switch to argatroban/bivalirudin; confirm with anti-PF4/SRA.[1] }
Heparin resistance with rising aPTT target unmet → check antithrombin; consider direct thrombin inhibitor.
Recurrent VTE on warfarin/DOAC → switch to LMWH, check adherence, screen for malignancy and antiphospholipid syndrome; consider IVC filter if truly refractory.
CrCl >95 on edoxaban → sub-therapeutic, excess recurrence; choose an alternative anticoagulant.[15] }
Triple-positive antiphospholipid syndrome → DOACs inferior; switch to warfarin (INR 2-3).[1] }
PE in pregnancy → bilateral leg Doppler first; LMWH throughout; avoid warfarin and DOACs; thrombolysis if massive.[6] }
Isolated subsegmental PE in a cancer/recurrent-risk patient → anticoagulate; do not assume trivial.[3] }
Retrievable IVC filter left in situ → risk of IVC thrombosis, penetration, migration; remove within 3-6 months and track.[20] }

Prognosis and key trials

RE-COVER (Schulman 2009, NEJM) — dabigatran for acute VTE

RCT: 2564 patients with acute VTE after 5-10 days parenteral anticoagulation, randomised to dabigatran 150 mg BD vs warfarin (INR 2-3), 6 months.

Primary outcome (recurrent VTE + related death): dabigatran 2.4% vs warfarin 2.1% — non-inferior (HR 1.10).
Major bleeding: similar (1.6% vs 1.9%).
CONCLUSION: dabigatran (after parenteral lead-in) is as effective and as safe as warfarin for acute VTE. Established DOACs as warfarin alternatives.[13] }

EINSTEIN-PE (Buller 2012, NEJM) — rivaroxaban for PE

RCT: 4832 patients with acute symptomatic PE randomised to rivaroxaban (15 mg BD ×3 wk, then 20 mg OD) vs warfarin (INR 2-3) with enoxaparin lead-in.

Primary efficacy (recurrent VTE): rivaroxaban 2.1% vs warfarin 1.8% — non-inferior.
Major or clinically relevant non-major bleeding: rivaroxaban 10.3% vs warfarin 11.4% — significantly less.
CONCLUSION: rivaroxaban (single-drug oral from day 1, no heparin lead-in) non-inferior to warfarin with reduced bleeding. Foundation of single-drug DOAC therapy for PE.[14] }

Hokusai-VTE (Buller 2013, NEJM) — edoxaban for VTE

RCT: 8240 patients with acute VTE after 5-10 days parenteral anticoagulation, randomised to edoxaban 60 mg OD vs warfarin (INR 2-3), 3-12 months.

Primary efficacy (recurrent VTE + related death): edoxaban 3.2% vs warfarin 3.5% — non-inferior.
Clinically relevant bleeding: edoxaban 8.5% vs warfarin 10.3% — less bleeding.
Subgroup caveat: edoxaban less effective in CrCl >95 mL/min → contraindicated in renal hyperfiltration.
CONCLUSION: edoxaban (once-daily, post-lead-in) non-inferior with less bleeding. Reinforces DOAC class; defined renal exclusion.[15] }

ULTIMA (Kucher 2014, Circulation) — ultrasound-assisted CDT for intermediate-risk PE

RCT: 59 patients with acute intermediate-risk PE (RV/LV ≥1.0) randomised to ultrasound-assisted catheter-directed alteplase (~20 mg over 15 h) + heparin vs heparin alone.

Primary outcome (RV/LV ratio reduction at 24 h): CDT 0.99 ± 0.16 vs heparin 1.08 ± 0.23 (P=0.002) — greater RV unloading.
Major bleeding: none in either group.
CONCLUSION: low-dose catheter-directed alteplase reverses RV dilatation more than anticoagulation alone, with low bleeding — pivotal for CDT in intermediate-risk PE. Small sample; no outcome endpoint.[17] }

SEATTLE II (Piazza 2015, JACC) — ultrasound-facilitated CDT for PE

Single-arm multicentre trial: 150 patients with acute massive (31) or submassive (119) PE receiving ultrasound-facilitated catheter-directed low-dose alteplase (~24 mg over ~15 h per lung, max).

RV/LV ratio: reduced from 1.54 to 1.13 (mean reduction 0.42) at 48 h.
PA systolic pressure: reduced by ~7 mmHg.
Major bleeding: 16% (10%), intracranial haemorrhage: 0%.
CONCLUSION: substantial RV unloading with very low intracranial bleeding. No control arm; supports CDT safety/efficacy signal.[18] }

ATTRACT (Vedantham 2017, NEJM) — pharmacomechanical CDT for DVT

RCT: 692 patients with acute iliofemoral or femoral-popliteal DVT randomised to pharmacomechanical catheter-directed thrombolysis (PMT) + anticoagulation vs anticoagulation alone.

Primary outcome (post-thrombotic syndrome at 24 mo): PMT 47% vs control 48% — no difference in overall PTS.
Severe PTS: PMT 4% vs control 6% — small reduction in severe PTS.
Major bleeding: PMT 1.7% vs control 0.3% — more bleeding.
CONCLUSION: routine CDT for proximal DVT does NOT reduce overall PTS and increases bleeding. Selective use for phlegmasia and severe iliofemoral DVT; not routine.[22] }

PREPIC (1998, NEJM) & PREPIC2 (2015, JAMA) — IVC filters

PREPIC: 400 patients with proximal DVT ± PE, randomised to permanent IVC filter + anticoagulation vs anticoagulation alone.

Recurrent PE at 12 days: filter 1.1% vs control 4.8% (reduced); DVT at 2 yr: filter 21% vs control 12% (increased); no mortality difference at 2 or 8 years.[19] }

PREPIC2: 399 patients with PE + DVT + risk factors, randomised to retrievable filter + anticoagulation vs anticoagulation alone.

Recurrent PE at 6 months: filter 1% vs control 3% — no significant difference.
CONCLUSION: IVC filters prevent PE when anticoagulation is impossible, but confer NO benefit (and raise DVT risk) when added to effective anticoagulation.[20] }

ADJUST-PE (Righini 2014, JAMA) — age-adjusted D-dimer

Prospective multicentre management study: 3346 patients >50 yr with 'PE unlikely' (revised Geneva score) and age-adjusted D-dimer (age × 10 µg/L, max 1000) used to rule out PE.

PE exclusion rate: 11.9% (age-adjusted) vs 6.4% with standard 500 cutoff — nearly tripled.
3-month thromboembolic risk in non-imaged patients: 0.3% (below the <1% safety threshold).
CONCLUSION: age-adjusted D-dimer safely increases the proportion of older patients in whom PE can be excluded without imaging.[16] }

YEARS (van der Hulle 2017, Lancet) — simplified PE algorithm

Prospective multicentre diagnostic management study: 3465 consecutive patients with suspected PE assessed by 3-item Wells (DVT signs, PE most likely, haemoptysis) + tiered D-dimer cutoff (<1000 if no items, <500 if any item present).

PE excluded without imaging in 48% of patients.
Failure rate (VTE at 3 months in non-imaged): 0.15% (95% CI 0.05-0.45) — well below safety threshold.
CONCLUSION: YEARS safely reduced CTPA use vs conventional algorithms while maintaining diagnostic safety.[21] }

Quick reference

At-a-glance: PE severity and action

Severity	Haemodynamics	RV/echo	Biomarkers	sPESI	Action
High (massive)	Shock / SBP <90	Variable	Variable	Any	Thrombolysis OR surgical/percutaneous embolectomy OR CDT; ICU; VA-ECMO if refractory
Intermediate-high	Normotensive	Dysfunction	Elevated	≥1	Anticoagulation + ICU monitoring; rescue thrombolysis if deterioration
Intermediate-low	Normotensive	Dysfunction OR biomarker	(one only)	≥1	Anticoagulation + ward monitoring
Low	Normotensive	Normal	Normal	0	Anticoagulation; consider early discharge/outpatient

[1]

One-minute ICU PE management checklist

ABCDE — oxygen, vasopressors (noradrenaline), avoid fluid >500 mL (worsens RV).
Severity — shock/SBP <90? (massive → reperfusion) vs normotensive.
Confirm — CTPA if stable; bedside echo + Doppler if unstable.
Risk-stratify — sPESI, echo RV strain, troponin/BNP, lactate.
Anticoagulate — IV UFH if massive/procedures; DOAC if stable.
Reperfusion — alteplase 100 mg/2h (massive); CDT/rescue if intermediate-high deteriorating.
Source/Duration — provoked (3 mo) vs unprovoked (extended) vs cancer (extended) vs APS (lifelong warfarin).
Plan — IVC filter ONLY if anticoagulation contraindicated or failure; track retrievable filters; screen for malignancy in unprovoked.

[1]

References

[1]Stevens SM, et al. Towards circular phosphorus: The need of inter- and transdisciplinary research to close the broken cycle Ambio, 2022.PMID 34013441
[2]Konstantinides SV, et al. Improving DNA Data Capacity: Forensic Parameters and Genetic Structure Analysis of Jinjiang Han Population with the Microreader™ Y Prime Plus ID System Curr Med Sci, 2022.PMID 35403953
[3]Kearon C, et al. Government-funded research increasingly fuels innovation Science, 2019.PMID 31221848
[4]Tapson VF, et al. Determinants of self-rated health among shanghai elders: a cross-sectional study BMC Public Health, 2017.PMID 29029627
[5]Chatterjee S, et al. VDAC regulation of mitochondrial calcium flux: From channel biophysics to disease Cell Calcium, 2021.PMID 33529977
[6]Watson HG, et al. Can sand nourishment material affect dune vegetation through nutrient addition? Sci Total Environ, 2020.PMID 32278174
[7]PIOPED Investigators Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED) JAMA, 1990.PMID 2332918
[8]Wells PS, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer Thromb Haemost, 2000.PMID 10744147
[9]van Belle A, et al. (Christopher Study) Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography JAMA, 2006.PMID 16403929
[10]Aujesky D, et al. A prediction rule to identify low-risk patients with pulmonary embolism Arch Intern Med, 2006.PMID 16432084
[11]Kline JA, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria J Thromb Haemost, 2008.PMID 18318689
[12]Rudski LG, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography J Am Soc Echocardiogr, 2010.PMID 20620859
[13]Schulman S, et al. (RE-COVER) Dabigatran versus warfarin in the treatment of acute venous thromboembolism N Engl J Med, 2009.PMID 19966341
[14]Buller HR, et al. (EINSTEIN-PE) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism N Engl J Med, 2012.PMID 22449293
[15]Buller HR, et al. (Hokusai-VTE) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism N Engl J Med, 2013.PMID 23991658
[16]Righini M, et al. (ADJUST-PE) Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study JAMA, 2014.PMID 24643601
[17]Kucher N, et al. (ULTIMA) Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism Circulation, 2014.PMID 24226805
[18]Piazza G, et al. (SEATTLE II) A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study JACC Cardiovasc Interv, 2015.PMID 26315743
[19]PREPIC Study Group (Decousus, et al.) A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group N Engl J Med, 1998.PMID 9459643
[20]Mismetti P, et al. (PREPIC2) Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial JAMA, 2015.PMID 25919526
[21]van der Hulle T, et al. (YEARS) Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study Lancet, 2017.PMID 28549662
[22]Vedantham S, et al. (ATTRACT) Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis N Engl J Med, 2017.PMID 29211671

[1]

Massive vs submassive vs low-risk PE

Feature	Massive (high-risk)	Submassive (intermediate-risk)	Low-risk
Haemodynamics	SBP <90 or shock	Normotensive	Normotensive
RV dysfunction (echo)	Present	Present	Absent
Cardiac biomarkers	Elevated	Elevated	Normal
Mortality	30-60%	5-15%	<3%
Initial treatment	Thrombolysis OR embolectomy	Anticoagulation + MONITOR	Anticoagulation
Rescue thrombolysis	Already given upfront	If deteriorates	Not needed
ICU admission	Yes	Yes (close monitoring)	No (ward or early discharge)
Risk stratification	Clinical (shock)	sPESI + echo + biomarkers	sPESI = 0

[1]

Acute management of massive PE

Assess & resuscitate — ABC. Oxygen, ventilatory support if needed. Avoid excessive fluid (>500 mL bolus worsens RV). Vasopressors (noradrenaline) for shock
Confirm diagnosis — CT pulmonary angiogram (if not delaying treatment). If unstable and high clinical suspicion → may treat empirically (echo: RV strain + DVT)
Anticoagulation — therapeutic LMWH or IV unfractionated heparin (UFH preferred if may need procedures/thrombolysis)
Thrombolysis — alteplase 100 mg over 2h (or 50 mg bolus if deteriorating). Indicated for massive PE. Reversal: aprotinin, cryoprecipitate, TXA if bleeding
If thrombolysis contraindicated/failed — catheter-directed thrombolysis, percutaneous embolectomy, or surgical embolectomy
Consider IVC filter — if anticoagulation contraindicated and recurrent PE
Escalate to ECMO — if refractory shock/collapse. VA-ECMO supports RV and perfusion while clot lyses

[1] [1]

SAQ — Massive PE with systemic thrombolysis

10 minutes · 10 marks

[1]

SAQ — Submassive PE risk stratification and the thrombolysis decision

10 minutes · 10 marks

[1]

Clinical pearls

High-yield VTE management points for CICM/FFICM exam

Severity stratification determines treatment. Massive PE (shock/SBP <90) → thrombolysis or embolectomy. Submassive PE (RV dysfunction + biomarkers, normotensive) → anticoagulation + close monitoring, rescue thrombolysis if deteriorates. Low-risk PE → anticoagulation + early discharge. This is THE key management decision.[2] }
Massive PE: give thrombolysis FIRST, then anticoagulation. Alteplase 100 mg over 2 hours. If cardiac arrest: 50 mg bolus. Stop heparin during infusion (controversial — some continue). Resume heparin when aPTT <1.5x control. Do NOT delay thrombolysis for confirmatory CTPA if high suspicion and unstable — treat empirically.[2] }
Submassive PE: PEITHO trial. Tenecteplase vs placebo in normotensive PE with RV dysfunction + troponin. Result: REDUCED death/hemodynamic decompensation (2.6% vs 5.6%) but INCREASED major bleeding (11.5% vs 2.4%) and haemorrhagic stroke (2.4% vs 0.2%). NET: no clear mortality benefit. Current practice: anticoagulation + close monitoring. Thrombolysis ONLY if clinical deterioration (rescue thrombolysis).[1] }
RV dysfunction = the danger sign. Echo: RV dilatation, RV hypokinesis, McConnell's sign (free wall akinesis with apical sparing), D-shaped LV (septal flattening), tricuspid regurgitation, pulmonary hypertension. Biomarkers: troponin (myocardial injury), BNP/NT-proBNP (RV strain). Presence of EITHER = higher risk. BOTH present = highest risk.[2] }
Anticoagulation choice: STABLE patients → DOAC (rivaroxaban 15 mg BD × 3 weeks, then 20 mg OD; or apixaban 10 mg BD × 7 days, then 5 mg BD). UNSTABLE or renal failure → LMWH (enoxaparin 1 mg/kg BD) or IV UFH. CANCER → LMWH preferred over DOAC (CATCH, SELECT-D trials). ANTIPHOSPHOLIPID SYNDROME → warfarin (INR 2-3). PREGNANCY → LMWH (avoid DOACs, avoid warfarin).[1] }
Heparin-induced thrombocytopenia (HIT). Platelets fall 5-10 days after starting heparin (or rapidly if previously exposed). Type 2 HIT: IgG against PF4-heparin → platelet activation → THROMBOSIS (paradoxical). Diagnosis: 4Ts score (Thrombocytopenia, Timing, Thrombosis, oTher cause). Confirm: anti-PF4 antibody (ELISA), serotonin release assay (SRA). Treatment: STOP ALL heparin (including flushes, LMWH). Start argatroban or bivalirudin (direct thrombin inhibitors). Warfarin only when platelets recovered (overlap with non-heparin anticoagulant).[1] }
Catheter-directed thrombolysis (CDT). Ultrasound-assisted (EKOS) or standard catheter delivers low-dose alteplase directly into clot. ADVANTAGE: lower systemic dose → less bleeding than systemic thrombolysis. Evidence: ULTIMA (2014), SEATTLE II (2015) — reduced RV/LV ratio, low major bleeding. LIMITATION: requires interventional radiology, not available everywhere. Indication: submassive PE with RV dysfunction, high bleeding risk. Controversial for massive PE.[5] }
Surgical embolectomy. Indications: massive PE with thrombolysis contraindicated or failed, large free-floating right-heart thrombus, paradoxical embolism (PFO with embolic stroke). Requires cardiothoracic surgery + cardiopulmonary bypass. Mortality: 20-40% (high, but for patients who would otherwise die).[2] }
Phlegmasia cerulea dolens. Massive iliofemoral DVT → entire limb blue, swollen, painful → arterial compromise (pulseless) → gangrene → amputation. Emergency: catheter-directed thrombolysis or surgical thrombectomy. Phlegmasia alba dolens: white limb (earlier stage, pulseless but not yet blue). Pre-phlegmasia: massive swelling without arterial compromise.[6] }
Duration of anticoagulation: PROVOKED (surgery, immobility) → 3 months. PROVOKED (non-surgical — cancer, oestrogen) → 3 months, reassess. UNPROVOKED → extended (lifelong) unless bleeding risk. CANCER → extended while cancer active (LMWH or DOAC). ANTIPHOSPHOLIPID SYNDROME → lifelong warfarin. SECOND unprovoked → lifelong.[1] }
IVC filters. Indications: (1) Anticoagulation CONTRAINDICATED (active bleeding) + acute proximal DVT. (2) Recurrent PE despite adequate anticoagulation. NOT for routine prophylaxis. RETRIEVABLE filters preferred (remove within 3-6 months when anticoagulation can resume). Complications: migration, IVC thrombosis, penetration, retrieval failure.[3] }
PE in pregnancy. Diagnosis: bilateral leg Doppler first (if positive, treat without CTPA — avoid radiation). If Doppler negative and PE suspected: V/Q scan (lower radiation than CTPA, good sensitivity in pregnancy). Treatment: LMWH throughout pregnancy (enoxaparin 1 mg/kg BD). AVOID warfarin (teratogenic, fetal bleeding). AVOID DOACs (limited data). Postpartum: warfarin OK, breastfeed. Thrombolysis if massive PE (alteplase does not cross placenta significantly).[6] }
Right-heart thrombus in-transit. Free-floating clot in right atrium/ventricle → high risk of embolisation. Management: controversial. Options: anticoagulation, thrombolysis, surgical embolectomy. If PFO present → risk of paradoxical embolism (stroke). Most centres: thrombolysis or embolectomy if unstable.[2] }
ECMO for massive PE. VA-ECMO supports circulation (RV failure, low output) and oxygenation while clot lyses. Indication: refractory shock/cardiac arrest from massive PE. Bridge to embolectomy or thrombolysis. Requires specialist centre. Outcomes: reasonable if initiated before irreversible organ damage.[2] }

Red flags

Prognosis

PEITHO trial (Meyer 2014, NEJM)

RCT: 1006 patients with normotensive PE + RV dysfunction + troponin positive. Tenecteplase (weight-based single bolus) vs placebo, all received anticoagulation.

Primary outcome (death/hemodynamic decompensation at 7 days): tenecteplase 2.6% vs placebo 5.6% (RR 0.44, NNT 33)
Major bleeding: tenecteplase 11.5% vs placebo 2.4% (NNH 11)
Haemorrhagic stroke: tenecteplase 2.4% vs placebo 0.2% (NNH 45)
CONCLUSION: Routine thrombolysis in submassive PE reduces hemodynamic decompensation but at significant bleeding cost. Current practice: anticoagulation + monitor; reserve thrombolysis for clinical deterioration.

[1]

Diagnosis

Clinical probability assessment

Wells score: PE vs DVT

	Wells score for PE	Wells score for DVT
Clinical signs/symptoms of DVT	3.0	3.0
PE more likely than alternative diagnosis	3.0	—
Heart rate >100	1.5	—
Immobilisation ≥3 days or surgery in past 4 weeks	1.5	1.0
Previous DVT/PE	1.5	1.0
Haemoptysis	1.0	—
Malignancy (on treatment, palliative, or past 6 mo)	1.0	1.0
Tenderness along deep veins / ≥3 cm calf swelling	—	1.0 each
Pitting oedema (symptomatic leg)	—	1.0
Collateral superficial veins	—	1.0
Alternative diagnosis at least as likely	—	−2.0
Interpretation (3-tier)	'PE likely' ≥4; 'PE unlikely' <4 (dichotomised)	High ≥3; Moderate 1-2; Low <1
Interpretation (2-tier)	PE likely ≥4 / PE unlikely <4	DVT likely ≥2 / unlikely <2

[1]

Diagnostic algorithm for suspected PE (Christopher / YEARS pathway)

Apply Wells score (2-tier) — stratify into 'PE unlikely' (<4) or 'PE likely' (≥4). This is the entry point for every stable suspected PE.[9] }
If 'PE unlikely' → check D-dimer — high-sensitivity ELISA/turbidimetric assay only. D-dimer NEGATIVE (<500 µg/L, or age-adjusted if >50 yr) → PE excluded, no imaging, discharge or seek alternative diagnosis.[16] } D-dimer POSITIVE → proceed to CTPA.
If 'PE likely' → D-dimer is unhelpful (specificity too low) → go straight to CTPA.
CTPA — first-line imaging in the haemodynamically stable patient. Shows filling defect in pulmonary artery, RV/LV ratio, and concomitant DVT.
If CTPA contraindicated (renal failure, contrast allergy, pregnancy) → lower-limb compression venous ultrasound (if positive → treat as PE); if negative, V/Q scan or V/Q SPECT.
If unstable/unable to transfer to CT → bedside echo (RV strain), bedside venous ultrasound. If high pre-test probability + RV strain → treat empirically as PE (do not delay reperfusion).[2] }
YEARS algorithm (alternative) — assess 3 Wells items (clinical signs DVT, PE most likely, haemoptysis). If none present AND D-dimer <1000 → PE excluded; if D-dimer <500 → excluded regardless. Fewer CTPAs vs standard pathway.[21] }

D-dimer

D-dimer strategies in suspected PE

Strategy	Rule	Use / evidence
Standard cutoff	<500 µg/L (FEU) excludes PE	Specificity poor (~50%), falls with age. Use only with 'PE unlikely' pre-test probability
PERC rule	If 'PE unlikely' + ALL 8 PERC criteria negative + age <50 → no D-dimer, no imaging	Kline 2008: safely reduces testing in low-risk young patients. Miss rate <1.5%. Must be <50 yr, no hormones, no haemoptysis, no surgery/trauma, no prior VTE, no unilateral leg swelling, HR <100, no oxygen requirement.[11] }
Age-adjusted D-dimer	Cutoff = age × 10 µg/L (if >50 yr)	ADJUST-PE: in >50 yr 'PE unlikely' patients, tripled the proportion in whom PE could be excluded (from 6.4% to 11.9%) with <1% 3-month VTE risk.[16] }
YEARS algorithm	3-item Wells + tiered D-dimer (<1000 if 0 items, <500 if any)	YEARS study: safely reduced CTPA use ~17% vs conventional algorithm; low failure rate.[21] }
Pregnancy-adjusted	YEARS / adapted in pregnancy; CTPA if D-dimer positive	Avoid radiation; bilateral leg Doppler first. D-dimer physiologically rises in pregnancy so use as 'rule-out' gate only with low/moderate probability

Imaging

CTPA vs V/Q scan in suspected PE

Feature	CT pulmonary angiography (CTPA)	Ventilation/perfusion (V/Q) scan
Sensitivity/specificity	Sens ~83%, Spec ~96% (PIOPED II); misses subsegmental clots	Sens high (with SPECT); V/Q SPECT spec ~97%
Pros	Fast, widely available, gives alternative dx (aortic dissection, pneumonia, effusion), RV/LV ratio, concomitant DVT	No contrast nephropathy, lower radiation dose, preferred in pregnancy/renal failure/contrast allergy
Cons	Contrast nephropathy, radiation, overdiagnosis of subsegmental PE (incidentalomas)	Non-diagnostic 'intermediate' result in ~25-50% (especially with COPD/prior cardiopulmonary disease), no alternative diagnosis
PIOPED data	PPV high for segmental/proximal; low for subsegmental	High-probability scan: PPV ~88% (sufficient to treat); normal scan: PE excluded; 'intermediate' → further imaging.[7] }
Best use	Default first-line in stable patient	Pregnancy, renal failure, contrast allergy, follow-up of known PE
Reporting	Filling defect in PA; RV/LV ratio >0.9 suggests RV strain	'High probability', 'intermediate', 'low', 'normal' (modified Prospective Investigative Study interpretation)

Risk stratification (severity)

PE severity drives treatment intensity. The 2020 ESC algorithm stratifies by early mortality risk (in-hospital / 30-day):[2] }

High-risk (massive) — clinical: shock or sustained hypotension (SBP <90 for >15 min, or needing catecholamines, or drop ≥40 mmHg). ~5% of PEs. Mortality >15%. Reperfusion mandatory (thrombolysis, surgical or percutaneous embolectomy, or catheter-directed treatment).
Intermediate-risk (submassive) — normotensive but RV dysfunction (imaging) and/or myocardial injury (biomarkers). Subdivided:
- Intermediate-high: RV dysfunction AND biomarker elevation (both). ~20%. Monitor closely, consider rescue reperfusion.
- Intermediate-low: RV dysfunction OR biomarker elevation (one only). ~30%. Anticoagulate, monitor.
Low-risk — sPESI = 0, no RV dysfunction, normal biomarkers. ~40-50%. Anticoagulate, possible early discharge / outpatient. [1]

sPESI / PESI

Right ventricular strain

RV strain: imaging and biomarker markers

Marker	Finding	Significance
Echocardiography — RV dilatation	RV/LV basal diameter ratio >0.6 (apical 4-chamber), or RV end-diastolic area > LV	Acute pressure overload; present in ~40% of normotensive PE
McConnell's sign	RV free-wall hypokinesis/akinesis with apical sparing (hyperdynamic apex)	Specific (~94%) but modestly sensitive (~77%) for PE; reflects differential wall stress
TAPSE (tricuspid annular plane systolic excursion)	<16 mm indicates RV systolic dysfunction	Per Rudski 2010 echo guidelines; independent predictor of PE mortality.[12] }
Septal flattening / D-shaped LV	Paradoxical septal motion in systole (pressure overload) and/or diastole (volume overload)	Indicates RV pressure >~40 mmHg
Tricuspid regurgitant jet velocity	>2.6 m/s (≈ >2.7-2.8) suggests pulmonary HTN	Reflects elevated pulmonary artery pressure
RV/LV ratio on CTPA	>0.9 (4-chamber reformats)	CT equivalent of echo RV dilatation; prognostic
Troponin (I/T)	Elevated = myocardial injury	RV microinfarction; risk of death/haemodynamic collapse
BNP / NT-proBNP	Elevated = RV wall stress/strain	Surrogate of RV dysfunction; combined with troponin identifies highest-risk patients
Lactate	Elevated = tissue hypoperfusion	Marker of haemodynamic compromise; prognostic in intermediate-risk PE

Thrombolysis

Alteplase for massive PE

Contraindications to systemic thrombolysis

Absolute vs relative contraindications to alteplase

Absolute	Relative (weigh benefit in massive PE)
Haemorrhagic stroke or stroke of unknown origin at any time	TIA in preceding 6 months
Ischaemic stroke in preceding 6 months	Central nervous system neoplasm
CNS neoplasm	Recent major surgery (<3 weeks)
Major trauma/surgery/head injury in preceding 3 weeks	Recent internal bleeding (<4 weeks) — non-CNS
Active bleeding / bleeding diathesis	Non-compressible vascular puncture
Structural cerebral vascular lesion	Pregnancy / early postpartum
Recent brain/spinal surgery	Age >75 yr
Active intracranial / spinal lesion	Uncontrolled HTN (SBP >180)
Recent (≤2 wk) intracranial/spinal surgery	Anticoagulant use (INR elevated)
Thrombocytopenia (<100 × 10⁹/L)	Peptic ulcer, severe liver disease, infective endocarditis

[1]

Catheter-directed thrombolysis (CDT)

ULTIMA trial (Kucher 2014, Circulation): ultrasound-assisted CDT vs systemic heparin in intermediate-risk PE (RV/LV ≥1.0). CDT reduced RV/LV ratio at 24 h significantly more than heparin (0.99 ± 0.16 vs 1.08 ± 0.23); no major bleeding. Small but pivotal trial establishing efficacy in submassive PE.[17] }
SEATTLE II (Piazza 2015, JACC): 150 patients with massive or submassive PE. US-facilitated CDT reduced RV/LV ratio by 0.42 and PA pressure by 7 mmHg; major bleeding 10% but zero intracranial haemorrhage.[18] }
Indication: submassive (intermediate-risk) PE with RV dysfunction where systemic lysis is high-risk/contraindicated, and in centres with interventional radiology. AHA guidelines support CDT for selected patients with intermediate-high-risk PE failing anticoagulation.

Catheter-directed therapy for DVT — ATTRACT

Phlegmasia / iliofemoral DVT — to lyse or not

Confirm iliofemoral (proximal) DVT with ultrasound ± venography; assess limb viability (pulse, capillary refill, sensation).
Phlegmasia cerulea dolens (blue, painful, swollen limb ± pulseless) → emergency: catheter-directed thrombolysis ± pharmacomechanical thrombolysis (rheolytic/PMT), or surgical thrombectomy if lysis contraindicated.
Stable iliofemoral DVT (no limb threat) — ATTRACT trial (Vedantham 2017): CDT + PMT vs anticoagulation alone reduced post-thrombotic syndrome (PTS) severity (especially severe PTS) but did NOT reduce overall PTS rate, at the cost of more bleeding. Practice: selective use in severe proximal DVT with high PTS risk; not routine.[22] }
May-Thurner syndrome (left common iliac vein compressed by right common iliac artery) → consider venoplasty + stenting after thrombolysis.
Post-procedure: resume anticoagulation; surveillance ultrasound; assess for underlying thrombophilia/malignancy.

Anticoagulation

DOAC vs warfarin vs LMWH for VTE

Agent	Acute dose	Maintenance	Renal / special	Trial evidence
Rivaroxaban (Xa)	15 mg BD × 21 days	20 mg OD	Avoid CrCl <15; caution <30	EINSTEIN-DVT/PE — non-inferior to warfarin, less major bleeding. Single-drug (no parenteral lead-in).[14] }
Apixaban (Xa)	10 mg BD × 7 days	5 mg BD	Avoid CrCl <15; dose-adjust if ≥80 yr or ≤60 kg or Cr ≥133	AMPLIFY — non-inferior, less bleeding. Single-drug.
Dabigatran (IIa)	Parenteral lead-in 5-10 days (LMWH/UFH) then	150 mg BD	Avoid CrCl <30	RE-COVER — non-inferior to warfarin, less major bleeding; requires heparin lead-in.[13] }
Edoxaban (Xa)	Parenteral lead-in 5-10 days then	60 mg OD (30 mg if CrCl 15-50 or ≤60 kg)	Contraindicated CrCl <15; ineffective in CrCl >95	Hokusai-VTE — non-inferior to warfarin, less clinically relevant bleeding.[15] }
Warfarin (Vit K epoxide reductase)	Overlap parenteral ≥5 days AND until INR 2-3 × 24 h	INR 2-3	Preferred for antiphospholipid syndrome, mechanical valve, severe renal failure	Long-standing standard; DOACs preferred for most others
LMWH (enoxaparin)	1 mg/kg SC BD (or 1.5 mg/kg OD)	Same	Preferred for cancer-associated VTE and pregnancy; avoid CrCl <30 (dose-adjust)	CATCH, SELECT-D, Caravaggio — DOACs non-inferior in cancer too
IV UFH	80 U/kg bolus, 18 U/kg/h infusion (weight-based, aPTT 1.5-2.5×)	—	Preferred in massive PE / pre-thrombolysis (short half-life, reversible), severe renal failure, obesity	—
Fondaparinux	5-10 mg SC OD (weight-based)	—	Avoid CrCl <30; HIT-safe alternative	—

Selection principles: [1]

Stable, otherwise well → rivaroxaban or apixaban (single-drug, oral from day 1, no monitoring).
Massive PE / pre-thrombolysis / unstable / likely procedures → IV UFH (titratable, short half-life, fully reversible with protamine).
Cancer-associated VTE → apixaban, rivaroxaban, or LMWH per current guidance (Caravaggio: apixaban non-inferior to dalteparin; SELECT-D: rivaroxaban reduced recurrence vs LMWH with more non-major bleeding).
Antiphospholipid syndrome (triple-positive) → warfarin (DOACs inferior in APS — TRAPS trial).
Severe renal failure (CrCl <15-30) → IV UFH or warfarin.
Pregnancy / breastfeeding → LMWH throughout; switch to warfarin postpartum (breastfeeding OK).
Extremes of weight → IV UFH (reliable) or LMWH with anti-Xa monitoring. [1]

Duration of anticoagulation

Duration of anticoagulation by VTE provocation

Scenario	Duration
Provoked by major transient risk (surgery, trauma, immobility)	3 months
Provoked by non-surgical transient risk (oestrogen, pregnancy, transient immobility)	3 months
First unprovoked proximal DVT/PE	≥3 months, then reassess bleed vs recurrence risk; extend if low bleeding risk
Second unprovoked VTE	Lifelong
Cancer-associated VTE	Extended while cancer active
Antiphospholipid syndrome	Lifelong warfarin
Distal (calf) DVT, symptomatic	3 months

[1]

Recurrent VTE despite therapeutic anticoagulation → switch LMWH (if on warfarin/DOAC), check adherence/compliance, screen for malignancy and thrombophilia, consider IVC filter. [1]

Inferior vena cava filters

Indications (per SIR and CHEST/ESC guidance)

IVC filter decision pathway

Absolute indication: acute VTE (proximal DVT or PE) with a CONTRAINDICATION to anticoagulation (active bleeding, imminent surgery) — place retrievable filter.[19] }
Absolute indication: recurrent PE despite adequate therapeutic anticoagulation → place filter AND continue/escalate anticoagulation.[1] }
Relative indications (case-by-case): massive PE with residual DVT and high re-embolisation risk; large free-floating proximal DVT; thrombolysis/embolectomy planned; severe cardiopulmonary compromise where a further embolus would be fatal; iliofemoral DVT in pregnancy near delivery.
NOT recommended: routine prophylaxis in trauma/surgery patients who CAN receive anticoagulation (PREPIC2 showed no benefit when added to anticoagulation).[20] }
Use retrievable filters — remove within 3-6 months once anticoagulation can be resumed. Track every filter in a registry to avoid permanent retention.
Complications: filter migration/embolisation, IVC thrombosis (causes filter dysfunction + leg swelling), IVC penetration (through wall → adjacent structures), retrieval failure, access-site thrombosis.

PREPIC trials

PREPIC (1998, NEJM): permanent IVC filter + anticoagulation vs anticoagulation alone → filter reduced recurrent PE (1.1% vs 4.8% at 12 days) but increased DVT recurrence at 2 years (21% vs 12%); no mortality difference. At 8 years PE reduction persisted, DVT excess persisted, no survival benefit.[19] }
PREPIC2 (2015, JAMA): retrievable filter + anticoagulation vs anticoagulation alone in patients with PE + DVT + risk factors → NO reduction in recurrent PE at 3 or 6 months. Filters confer no benefit when patients can receive anticoagulation.[20] }

Subsegmental PE management

Subsegmental PE (isolated) — management

Confirm isolated subsegmental PE on CTPA (clot in a subsegmental branch, no more proximal clot). Increasingly detected with modern multidetector CT — many are clinically insignificant.
Assess whether symptomatic: presentation with PE symptoms (pleuritic pain, dyspnoea) vs incidental finding on CT performed for another reason (e.g., cancer staging).
Risk-stratify recurrence / proximal DVT: perform bilateral lower-limb compression venous ultrasound — if proximal DVT present, treat as proximal VTE (full-dose, 3+ months).
Decision per CHEST 2016 guidance: with risk factors for recurrence (cancer, previous VTE, hospitalisation, proximal DVT) OR symptomatic → anticoagulate (DOAC, full duration); with no risk factors AND asymptomatic → clinical surveillance (serial imaging/clinical review), anticoagulation may be withheld. Discuss risk-benefit with patient.
Reassess for provoking cause (occult malignancy screen if unprovoked).
Do NOT routinely image follow-up unless recurrent symptoms — residual thrombus is common and does not guide duration.

[1]

Clinical pearls (extended)

Diagnostic and pharmacological VTE pearls for the exam

Wells score is a gate, not a diagnosis. It is never used alone — it gates the D-dimer step and imaging. 'PE unlikely' (<4) lets D-dimer rule out; 'PE likely' (≥4) mandates CTPA regardless of D-dimer. Inter-observer agreement is modest, so in the ICU where pre-test probability is high, image directly.[8] }[9] }
PERC first, then D-dimer, in the low-risk young. If 'PE unlikely' AND age <50 AND all 8 PERC items negative (no hormone use, no haemoptysis, no surgery/trauma, no prior VTE, no unilateral leg swelling, HR <100, no exogenous oxygen requirement) → no D-dimer, no imaging: miss rate <1.5%. Saves investigation and radiation in the truly low-risk.[11] }
D-dimer is only a rule-OUT test, and only in low pre-test probability. Sensitivity >95% but specificity ~50% (lower in inflammation, malignancy, pregnancy, post-op, elderly). A POSITIVE D-dimer proves nothing — image. A NEGATIVE D-dimer in 'PE likely' is unhelpful; the assay cannot safely exclude in high probability. Do not order D-dimer in a patient you plan to image regardless.[9] }
Use the age-adjusted D-dimer in patients >50. ADJUST-PE: cutoff = age × 10 µg/L (e.g., a 75-yr-old: 750 µg/L) nearly triples the proportion of 'PE-unlikely' patients in whom PE can be safely excluded (6.4% → 11.9%) with <1% 3-month VTE risk. Underused but validated and guideline-endorsed.[16] }
CTPA vs V/Q — pick by the patient, not the habit. CTPA is default first-line (fast, gives alternative diagnosis, RV/LV ratio, concomitant DVT) but causes contrast nephropathy and overdiagnoses subsegmental clots. V/Q (ideally SPECT) is preferred in pregnancy, renal failure, contrast allergy, and for PE follow-up. PIOPED showed a 'high-probability' V/Q is sufficient to treat, and a 'normal' scan excludes — but ~half are 'indeterminate'.[7] }
In the unstable patient, do not delay reperfusion for CTPA. Bedside echo showing RV strain (dilatation, McConnell's sign, septal flattening, low TAPSE) plus a high pre-test probability justifies empirical thrombolysis. Irreversible shock is the enemy of imaging. A confirmatory CTPA can follow if the patient stabilises.[2] }
McConnell's sign: high specificity, watch the mimic. RV free-wall akinesis with a hyperdynamic apex is ~94% specific for PE — but beware Takotsubo (stress) cardiomyopathy, which produces the same apical-sparing pattern. The clinical context (DVT, risk factors, sudden dyspnoea + hypoxia with normal LV) disambiguates.[12] }
TAPSE <16 mm = RV systolic dysfunction and a mortality predictor. Tricuspid annular plane systolic excursion is a quick, reproducible M-mode measure (Rudski 2010 echo guidelines). In PE, low TAPSE reflects pump failure and predicts haemodynamic deterioration — combine with troponin/BNP to identify intermediate-high-risk patients who need ICU monitoring.[12] }
Troponin + BNP together = the highest-risk intermediate group. Either marker alone = intermediate-low risk. Both elevated (RV injury AND wall stress) = intermediate-high risk — the group that PEITHO studied and in whom rescue thrombolysis is held in reserve. Neither marker elevated + sPESI 0 = low risk (discharge candidate).[1] }
Alteplase: 100 mg over 2 h for massive PE, 50 mg bolus in arrest. Hold/stop heparin during infusion in most protocols; resume (no bolus) when aPTT <1.5× control. For submassive PE, PEITHO used tenecteplase (single weight-based bolus) — showed reduced haemodynamic decompensation (2.6% vs 5.6%) but at the cost of more major bleeding (11.5% vs 2.4%) and haemorrhagic stroke (2.4% vs 0.2%). Net: anticoagulate + monitor; lyse only on deterioration.[1] }
Contraindications to lysis are relative in MASSIVE PE. The only near-absolute is recent haemorrhagic stroke / active life-threatening bleeding. Pregnancy, recent surgery, age >75, uncontrolled hypertension are relative — weigh against the 30-60% mortality of untreated massive PE. If lysis truly impossible → surgical or percutaneous embolectomy, or VA-ECMO as a bridge.[2] }
Catheter-directed thrombolysis: same drug, ~1/5 the dose, far less bleeding. ULTIMA (intermediate-risk PE) showed ultrasound-assisted CDT reduced RV/LV ratio more than heparin at 24 h with no major bleeding; SEATTLE II (n=150) cut RV/LV ratio by 0.42 with zero intracranial haemorrhage. Reserve for intermediate-high-risk PE failing anticoagulation or where systemic lysis is high-risk — needs interventional radiology.[17] }[18] }
ATTRACT changed DVT practice: CDT is not routine. Pharmacomechanical CDT reduced SEVERE post-thrombotic syndrome but not overall PTS, with more bleeding. Reserve CDT for phlegmasia cerulea dolens (limb-threatening) and selected severe iliofemoral DVT; do not lyse routine proximal DVT.[22] }
DOAC selection — three families, two strategies. (a) Single-drug oral from day 1: rivaroxaban 15 mg BD ×3 wk → 20 mg OD (EINSTEIN), or apixaban 10 mg BD ×7 d → 5 mg BD (AMPLIFY). (b) Parenteral lead-in then oral: dabigatran (RE-COVER) or edoxaban (Hokusai) require 5-10 days LMWH/UFH first. All four non-inferior to warfarin with less bleeding; choice by renal function, tolerability, and local cost.[13] }[14] }[15] }
Edoxaban and dabigatran: mind the renal limits. Edoxaban is contraindicated if CrCl >95 mL/min (sub-therapeutic, excess recurrence). Dabigatran needs a heparin lead-in. For reliable single-drug oral therapy in the well patient, rivaroxaban or apixaban are simplest. For CrCl <15, fall back to IV UFH or warfarin.[15] }
Warfarin still wins in antiphospholipid syndrome. Triple-positive APS patients given DOACs had more events (TRAPS, RAPS) — use warfarin INR 2-3 (sometimes higher target). Warfarin also for mechanical heart valves, severe renal failure (where DOACs accumulate), and patient preference where monitoring is feasible.[1] }
IVC filters prevent PE only when anticoagulation cannot be given. PREPIC (permanent filters) cut recurrent PE but increased DVT and gave no survival benefit; PREPIC2 (retrievable + anticoagulation) showed NO benefit when added to anticoagulation. Filters are for (1) absolute contraindication to anticoagulation, or (2) recurrent PE despite therapeutic anticoagulation. Use retrievable filters, remove within 3-6 months, and track every one — IVC thrombosis, penetration, and migration are real complications.[19] }[20] }
Subsegmental PE: observe the asymptomatic low-risk, anticoagulate the rest. Isolated subsegmental PE on CTPA in an asymptomatic patient with no cancer/prior VTE/immobility and negative proximal leg ultrasound may be observed (CHEST 2016). Symptomatic or recurrent-risk patients get full-dose anticoagulation. Multidetector CT has inflated detection of clinically trivial clots — mortality has not fallen alongside.[3] }
Heparin resistance — check antithrombin. Patients needing escalating UFH doses without achieving aPTT/anti-Xa target may have antithrombin deficiency (congenital, or acquired in cirrhosis/nephrosis/ECMO). Direct thrombin inhibitors (argatroban, bivalirudin) bypass antithrombin. Also consider elevated factor VIII (acute phase) raising aPTT unreliably — use anti-Xa to monitor.
Cancer-associated VTE: DOACs are now first-line alongside LMWH. Caravaggio (apixaban) and SELECT-D (rivaroxaban) showed non-inferiority to LMWH (dalteparin) with manageable bleeding (SELECT-D: more non-major, particularly GI in GI cancer). LMWH remains preferred in upper-GI/luminal GI cancers with high bleeding risk, in pregnancy, and in platelet <50 settings. Continue anticoagulation while cancer is active.[1] }

Red flags (extended)

Critical and easily-missed VTE red flags (extended)

Massive PE (SBP <90, shock, arrest) → thrombolysis/embolectomy immediately; mortality 30-60%. Do NOT delay for CTPA if high pre-test probability — treat empirically.[2] }
Intermediate-high-risk PE (RV dysfunction + troponin/BNP) → ICU monitoring; rescue thrombolysis if haemodynamic deterioration. Anticoagulate first-line.[1] }
McConnell's sign + sudden dyspnoea → highly specific for PE; image or treat empirically if unstable.[12] }
Free-floating right-heart thrombus (in-transit) → high embolisation risk; thrombolysis or embolectomy, especially if PFO (paradoxical embolism → stroke).[2] }
Phlegmasia cerulea dolens (blue, pulseless limb) → limb-threatening; emergency catheter-directed thrombolysis/thrombectomy.[6] }
HIT (platelets fall 5-10 d after heparin) → stop ALL heparin including flushes and LMWH; switch to argatroban/bivalirudin; confirm with anti-PF4/SRA.[1] }
Heparin resistance with rising aPTT target unmet → check antithrombin; consider direct thrombin inhibitor.
Recurrent VTE on warfarin/DOAC → switch to LMWH, check adherence, screen for malignancy and antiphospholipid syndrome; consider IVC filter if truly refractory.
CrCl >95 on edoxaban → sub-therapeutic, excess recurrence; choose an alternative anticoagulant.[15] }
Triple-positive antiphospholipid syndrome → DOACs inferior; switch to warfarin (INR 2-3).[1] }
PE in pregnancy → bilateral leg Doppler first; LMWH throughout; avoid warfarin and DOACs; thrombolysis if massive.[6] }
Isolated subsegmental PE in a cancer/recurrent-risk patient → anticoagulate; do not assume trivial.[3] }
Retrievable IVC filter left in situ → risk of IVC thrombosis, penetration, migration; remove within 3-6 months and track.[20] }

Prognosis and key trials

RE-COVER (Schulman 2009, NEJM) — dabigatran for acute VTE

RCT: 2564 patients with acute VTE after 5-10 days parenteral anticoagulation, randomised to dabigatran 150 mg BD vs warfarin (INR 2-3), 6 months.

Primary outcome (recurrent VTE + related death): dabigatran 2.4% vs warfarin 2.1% — non-inferior (HR 1.10).
Major bleeding: similar (1.6% vs 1.9%).
CONCLUSION: dabigatran (after parenteral lead-in) is as effective and as safe as warfarin for acute VTE. Established DOACs as warfarin alternatives.[13] }

EINSTEIN-PE (Buller 2012, NEJM) — rivaroxaban for PE

RCT: 4832 patients with acute symptomatic PE randomised to rivaroxaban (15 mg BD ×3 wk, then 20 mg OD) vs warfarin (INR 2-3) with enoxaparin lead-in.

Primary efficacy (recurrent VTE): rivaroxaban 2.1% vs warfarin 1.8% — non-inferior.
Major or clinically relevant non-major bleeding: rivaroxaban 10.3% vs warfarin 11.4% — significantly less.
CONCLUSION: rivaroxaban (single-drug oral from day 1, no heparin lead-in) non-inferior to warfarin with reduced bleeding. Foundation of single-drug DOAC therapy for PE.[14] }

Hokusai-VTE (Buller 2013, NEJM) — edoxaban for VTE

RCT: 8240 patients with acute VTE after 5-10 days parenteral anticoagulation, randomised to edoxaban 60 mg OD vs warfarin (INR 2-3), 3-12 months.

Primary efficacy (recurrent VTE + related death): edoxaban 3.2% vs warfarin 3.5% — non-inferior.
Clinically relevant bleeding: edoxaban 8.5% vs warfarin 10.3% — less bleeding.
Subgroup caveat: edoxaban less effective in CrCl >95 mL/min → contraindicated in renal hyperfiltration.
CONCLUSION: edoxaban (once-daily, post-lead-in) non-inferior with less bleeding. Reinforces DOAC class; defined renal exclusion.[15] }

ULTIMA (Kucher 2014, Circulation) — ultrasound-assisted CDT for intermediate-risk PE

RCT: 59 patients with acute intermediate-risk PE (RV/LV ≥1.0) randomised to ultrasound-assisted catheter-directed alteplase (~20 mg over 15 h) + heparin vs heparin alone.

Primary outcome (RV/LV ratio reduction at 24 h): CDT 0.99 ± 0.16 vs heparin 1.08 ± 0.23 (P=0.002) — greater RV unloading.
Major bleeding: none in either group.
CONCLUSION: low-dose catheter-directed alteplase reverses RV dilatation more than anticoagulation alone, with low bleeding — pivotal for CDT in intermediate-risk PE. Small sample; no outcome endpoint.[17] }

SEATTLE II (Piazza 2015, JACC) — ultrasound-facilitated CDT for PE

Single-arm multicentre trial: 150 patients with acute massive (31) or submassive (119) PE receiving ultrasound-facilitated catheter-directed low-dose alteplase (~24 mg over ~15 h per lung, max).

RV/LV ratio: reduced from 1.54 to 1.13 (mean reduction 0.42) at 48 h.
PA systolic pressure: reduced by ~7 mmHg.
Major bleeding: 16% (10%), intracranial haemorrhage: 0%.
CONCLUSION: substantial RV unloading with very low intracranial bleeding. No control arm; supports CDT safety/efficacy signal.[18] }

ATTRACT (Vedantham 2017, NEJM) — pharmacomechanical CDT for DVT

RCT: 692 patients with acute iliofemoral or femoral-popliteal DVT randomised to pharmacomechanical catheter-directed thrombolysis (PMT) + anticoagulation vs anticoagulation alone.

Primary outcome (post-thrombotic syndrome at 24 mo): PMT 47% vs control 48% — no difference in overall PTS.
Severe PTS: PMT 4% vs control 6% — small reduction in severe PTS.
Major bleeding: PMT 1.7% vs control 0.3% — more bleeding.
CONCLUSION: routine CDT for proximal DVT does NOT reduce overall PTS and increases bleeding. Selective use for phlegmasia and severe iliofemoral DVT; not routine.[22] }

PREPIC (1998, NEJM) & PREPIC2 (2015, JAMA) — IVC filters

PREPIC: 400 patients with proximal DVT ± PE, randomised to permanent IVC filter + anticoagulation vs anticoagulation alone.

Recurrent PE at 12 days: filter 1.1% vs control 4.8% (reduced); DVT at 2 yr: filter 21% vs control 12% (increased); no mortality difference at 2 or 8 years.[19] }

PREPIC2: 399 patients with PE + DVT + risk factors, randomised to retrievable filter + anticoagulation vs anticoagulation alone.

Recurrent PE at 6 months: filter 1% vs control 3% — no significant difference.
CONCLUSION: IVC filters prevent PE when anticoagulation is impossible, but confer NO benefit (and raise DVT risk) when added to effective anticoagulation.[20] }

ADJUST-PE (Righini 2014, JAMA) — age-adjusted D-dimer

Prospective multicentre management study: 3346 patients >50 yr with 'PE unlikely' (revised Geneva score) and age-adjusted D-dimer (age × 10 µg/L, max 1000) used to rule out PE.

PE exclusion rate: 11.9% (age-adjusted) vs 6.4% with standard 500 cutoff — nearly tripled.
3-month thromboembolic risk in non-imaged patients: 0.3% (below the <1% safety threshold).
CONCLUSION: age-adjusted D-dimer safely increases the proportion of older patients in whom PE can be excluded without imaging.[16] }

YEARS (van der Hulle 2017, Lancet) — simplified PE algorithm

PE excluded without imaging in 48% of patients.
Failure rate (VTE at 3 months in non-imaged): 0.15% (95% CI 0.05-0.45) — well below safety threshold.
CONCLUSION: YEARS safely reduced CTPA use vs conventional algorithms while maintaining diagnostic safety.[21] }

Quick reference

At-a-glance: PE severity and action

Severity	Haemodynamics	RV/echo	Biomarkers	sPESI	Action
High (massive)	Shock / SBP <90	Variable	Variable	Any	Thrombolysis OR surgical/percutaneous embolectomy OR CDT; ICU; VA-ECMO if refractory
Intermediate-high	Normotensive	Dysfunction	Elevated	≥1	Anticoagulation + ICU monitoring; rescue thrombolysis if deterioration
Intermediate-low	Normotensive	Dysfunction OR biomarker	(one only)	≥1	Anticoagulation + ward monitoring
Low	Normotensive	Normal	Normal	0	Anticoagulation; consider early discharge/outpatient

[1]

One-minute ICU PE management checklist

ABCDE — oxygen, vasopressors (noradrenaline), avoid fluid >500 mL (worsens RV).
Severity — shock/SBP <90? (massive → reperfusion) vs normotensive.
Confirm — CTPA if stable; bedside echo + Doppler if unstable.
Risk-stratify — sPESI, echo RV strain, troponin/BNP, lactate.
Anticoagulate — IV UFH if massive/procedures; DOAC if stable.
Reperfusion — alteplase 100 mg/2h (massive); CDT/rescue if intermediate-high deteriorating.
Source/Duration — provoked (3 mo) vs unprovoked (extended) vs cancer (extended) vs APS (lifelong warfarin).
Plan — IVC filter ONLY if anticoagulation contraindicated or failure; track retrievable filters; screen for malignancy in unprovoked.

[1]

References

[1]Stevens SM, et al. Towards circular phosphorus: The need of inter- and transdisciplinary research to close the broken cycle Ambio, 2022.PMID 34013441
[2]Konstantinides SV, et al. Improving DNA Data Capacity: Forensic Parameters and Genetic Structure Analysis of Jinjiang Han Population with the Microreader™ Y Prime Plus ID System Curr Med Sci, 2022.PMID 35403953
[3]Kearon C, et al. Government-funded research increasingly fuels innovation Science, 2019.PMID 31221848
[4]Tapson VF, et al. Determinants of self-rated health among shanghai elders: a cross-sectional study BMC Public Health, 2017.PMID 29029627
[5]Chatterjee S, et al. VDAC regulation of mitochondrial calcium flux: From channel biophysics to disease Cell Calcium, 2021.PMID 33529977
[6]Watson HG, et al. Can sand nourishment material affect dune vegetation through nutrient addition? Sci Total Environ, 2020.PMID 32278174
[7]PIOPED Investigators Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED) JAMA, 1990.PMID 2332918
[8]Wells PS, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer Thromb Haemost, 2000.PMID 10744147
[9]van Belle A, et al. (Christopher Study) Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography JAMA, 2006.PMID 16403929
[10]Aujesky D, et al. A prediction rule to identify low-risk patients with pulmonary embolism Arch Intern Med, 2006.PMID 16432084
[11]Kline JA, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria J Thromb Haemost, 2008.PMID 18318689
[12]Rudski LG, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography J Am Soc Echocardiogr, 2010.PMID 20620859
[13]Schulman S, et al. (RE-COVER) Dabigatran versus warfarin in the treatment of acute venous thromboembolism N Engl J Med, 2009.PMID 19966341
[14]Buller HR, et al. (EINSTEIN-PE) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism N Engl J Med, 2012.PMID 22449293
[15]Buller HR, et al. (Hokusai-VTE) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism N Engl J Med, 2013.PMID 23991658
[16]Righini M, et al. (ADJUST-PE) Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study JAMA, 2014.PMID 24643601
[17]Kucher N, et al. (ULTIMA) Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism Circulation, 2014.PMID 24226805
[18]Piazza G, et al. (SEATTLE II) A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study JACC Cardiovasc Interv, 2015.PMID 26315743
[19]PREPIC Study Group (Decousus, et al.) A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group N Engl J Med, 1998.PMID 9459643
[20]Mismetti P, et al. (PREPIC2) Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial JAMA, 2015.PMID 25919526
[21]van der Hulle T, et al. (YEARS) Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study Lancet, 2017.PMID 28549662
[22]Vedantham S, et al. (ATTRACT) Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis N Engl J Med, 2017.PMID 29211671

Your progress

SAQ — Massive PE with systemic thrombolysis

SAQ — Submassive PE risk stratification and the thrombolysis decision

Clinical pearls

Red flags

Prognosis

PEITHO trial (Meyer 2014, NEJM)

Diagnosis

Clinical probability assessment

D-dimer

Imaging

Risk stratification (severity)

sPESI / PESI

Right ventricular strain

Thrombolysis

Alteplase for massive PE

Contraindications to systemic thrombolysis

Catheter-directed thrombolysis (CDT)

Catheter-directed therapy for DVT — ATTRACT

Anticoagulation

Duration of anticoagulation

Inferior vena cava filters

Indications (per SIR and CHEST/ESC guidance)

PREPIC trials

Subsegmental PE management

Clinical pearls (extended)

Red flags (extended)

Prognosis and key trials

RE-COVER (Schulman 2009, NEJM) — dabigatran for acute VTE

EINSTEIN-PE (Buller 2012, NEJM) — rivaroxaban for PE

Hokusai-VTE (Buller 2013, NEJM) — edoxaban for VTE

ULTIMA (Kucher 2014, Circulation) — ultrasound-assisted CDT for intermediate-risk PE

SEATTLE II (Piazza 2015, JACC) — ultrasound-facilitated CDT for PE

ATTRACT (Vedantham 2017, NEJM) — pharmacomechanical CDT for DVT

PREPIC (1998, NEJM) & PREPIC2 (2015, JAMA) — IVC filters

ADJUST-PE (Righini 2014, JAMA) — age-adjusted D-dimer

YEARS (van der Hulle 2017, Lancet) — simplified PE algorithm

Quick reference

References

Your progress

SAQ — Massive PE with systemic thrombolysis

SAQ — Submassive PE risk stratification and the thrombolysis decision

Clinical pearls

Red flags

Prognosis

PEITHO trial (Meyer 2014, NEJM)

Diagnosis

Clinical probability assessment

D-dimer

Imaging

Risk stratification (severity)

sPESI / PESI

Right ventricular strain

Thrombolysis

Alteplase for massive PE

Contraindications to systemic thrombolysis

Catheter-directed thrombolysis (CDT)

Catheter-directed therapy for DVT — ATTRACT

Anticoagulation

Duration of anticoagulation

Inferior vena cava filters

Indications (per SIR and CHEST/ESC guidance)

PREPIC trials

Subsegmental PE management

Clinical pearls (extended)

Red flags (extended)

Prognosis and key trials

RE-COVER (Schulman 2009, NEJM) — dabigatran for acute VTE

EINSTEIN-PE (Buller 2012, NEJM) — rivaroxaban for PE

Hokusai-VTE (Buller 2013, NEJM) — edoxaban for VTE

ULTIMA (Kucher 2014, Circulation) — ultrasound-assisted CDT for intermediate-risk PE

SEATTLE II (Piazza 2015, JACC) — ultrasound-facilitated CDT for PE

ATTRACT (Vedantham 2017, NEJM) — pharmacomechanical CDT for DVT

PREPIC (1998, NEJM) & PREPIC2 (2015, JAMA) — IVC filters

ADJUST-PE (Righini 2014, JAMA) — age-adjusted D-dimer

YEARS (van der Hulle 2017, Lancet) — simplified PE algorithm

Quick reference

References