282.1 🎓 醫學生版

282.1.0.1 📌 一頁重點

282.1.0.1.1 Epidemiology

• VTE incidence ~ 1-2 per 1,000 person-years
• DVT 2x more common than PE
• ~ 30% of VTE develops PE; ~ 10-30% of PE fatal
• 1-month mortality 6-12%; 3-month ~ 15%
• Recurrence risk: 30% over 10 years if unprovoked

282.1.0.1.2 Virchow’s Triad

282.1.0.1.2.1 Stasis (Slow Flow)

• Immobility (bed rest, long flights/drives)
• HF, recent surgery
• Pregnancy / postpartum
• Obesity, advanced age

282.1.0.1.2.2 Hypercoagulability

• Inherited:
  • Factor V Leiden (most common, 5% Caucasians) — APC resistance
  • Prothrombin G20210A
  • Protein C, S, antithrombin deficiency
• Acquired:
  • Antiphospholipid syndrome (APS) — lupus anticoagulant, anticardiolipin, anti-β2-GPI
  • Malignancy (paraneoplastic, TF expression)
  • Pregnancy / OCP / HRT (estrogen)
  • Heparin-induced thrombocytopenia (HIT)
  • Nephrotic syndrome (loss of antithrombin)
  • PNH (paroxysmal nocturnal hemoglobinuria)
  • JAK2-positive MPNs

282.1.0.1.2.3 Endothelial Injury

• Surgery, trauma
• Indwelling catheters
• Vasculitis, infection
• Atherosclerosis

282.1.0.1.3 Clinical Presentation

282.1.0.1.3.1 DVT

• Proximal DVT (popliteal/femoral/iliac):
  • Unilateral leg swelling, warmth, redness, tenderness
  • Calf circumference > 3 cm asymmetry
  • Phlegmasia cerulea dolens: massive iliofemoral, cyanotic + cold (limb-threatening)
  • Phlegmasia alba dolens: pale variant
• Distal DVT (calf):
  • Often asymptomatic
  • Less likely to embolize (but can extend)

282.1.0.1.3.2 PE

• Symptoms: dyspnea, pleuritic chest pain, hemoptysis, syncope, palpitations, cough
• Signs: tachypnea, tachycardia, hypoxia, hypotension (massive), JVD, R-sided S3
• Massive PE: hemodynamic instability (SBP < 90 or pressors)
• Submassive (intermediate-high): RV dysfunction + cardiac biomarkers
• Low-risk: no instability, no RV dysfunction

282.1.0.1.4 Diagnostic Pathways

282.1.0.1.4.1 Wells Score for DVT

• Active cancer (1)
• Paralysis, paresis (1)
• Recently bedridden ≥ 3 days or major surgery in 4 wk (1)
• Localized tenderness along deep veins (1)
• Entire leg swollen (1)
• Calf > 3 cm than other (1)
• Pitting edema (1)
• Collateral superficial veins (1)
• Previous documented DVT (1)
• Alternative dx as likely or more (-2)
• Score: ≤ 0 low; 1-2 moderate; ≥ 3 high

282.1.0.1.4.2 Wells Score for PE

• Clinical DVT signs (3)
• PE more likely than alternative (3)
• HR > 100 (1.5)
• Immobilization or surgery in last 4 wk (1.5)
• Previous DVT/PE (1.5)
• Hemoptysis (1)
• Malignancy (1)
• Score: < 2 low; 2-6 moderate; > 6 high
• Two-level: ≤ 4 unlikely; > 4 likely

282.1.0.1.4.3 D-dimer

• High NPV; useful for low pretest probability
• Age-adjusted: age × 10 in μg/L (FDP)
• High false positive: surgery, cancer, pregnancy, infection, inflammation
• YEARS algorithm: combines Wells items + D-dimer for PE

282.1.0.1.4.4 Imaging

• DVT: compression duplex ultrasound (gold standard)
• PE:
  • CTPA: gold standard, fast
  • V/Q scan: alternative if contrast contraindicated, pregnancy
  • MR pulmonary angiography: emerging
  • TTE: for hemodynamic instability or risk stratification
• Pelvic / IVC / upper extremity DVT: CT or MR venography

282.1.0.1.5 Risk Stratification of PE (ESC 2019/2024)

282.1.0.1.5.1 High-Risk (Massive)

• Hemodynamic instability (SBP < 90 / pressors / shock / cardiac arrest)
• Treatment: systemic thrombolysis or catheter-directed therapy

282.1.0.1.5.2 Intermediate-High (Submassive)

• Hemodynamic stable but with RV dysfunction (echo or CTPA) AND elevated cardiac biomarkers (troponin or BNP)
• Risk of deterioration
• Consider catheter-directed therapy or rescue thrombolysis if worsening

282.1.0.1.5.3 Intermediate-Low (Submassive)

• Either RV dysfunction OR biomarker elevation (not both)
• Anticoagulation; close monitoring

282.1.0.1.5.4 Low-Risk

• No instability, no RV dysfunction, no biomarker elevation
• PESI / sPESI for risk score
• Anticoagulation; outpatient consideration

282.1.0.1.5.5 sPESI (simplified PESI)

• Age > 80 (1)
• Cancer (1)
• Chronic cardiopulmonary disease (1)
• HR ≥ 110 (1)
• SBP < 100 (1)
• O₂ sat < 90% (1)
• Score 0 = low-risk; ≥ 1 = higher risk

282.1.0.1.6 Treatment

282.1.0.1.6.1 Anticoagulation Choices

DOAC (Direct Oral Anticoagulants) — first-line for most - Apixaban 10 mg BID × 7d → 5 mg BID (AMPLIFY) — no parenteral lead-in - Rivaroxaban 15 mg BID × 21d → 20 mg daily (EINSTEIN) — no parenteral lead-in - Edoxaban 60 mg daily after 5-10 d parenteral lead-in - Dabigatran 150 mg BID after 5-10 d parenteral lead-in - DOACs ≈ warfarin for efficacy, ↓ bleeding (especially ICH) - Renal dose adjustments - Avoid in: CrCl < 15-30 (depends on agent), severe liver disease, mechanical valve, pregnancy, antiphospholipid syndrome (controversial — caution)

Warfarin - Bridge with parenteral (UFH/LMWH/fondaparinux) until INR 2-3 for 2 days - Indications: mechanical valve, APS (esp triple positive), severe renal disease - Drug interactions abundant

LMWH (Enoxaparin) - 1 mg/kg SC BID or 1.5 mg/kg SC daily - First-line in cancer-associated VTE historically (CLOT 2003) - DOAC now alternative (Hokusai-Cancer, SELECT-D, Caravaggio)

Fondaparinux - 7.5 mg SC daily - Alternative parenteral - Useful in HIT

UFH (IV) - Bolus + infusion, target aPTT 60-80 or anti-Xa 0.3-0.7 - For hemodynamic instability, renal failure, periprocedural

282.1.0.1.6.2 Duration of Anticoagulation

Provoked (Transient Risk Factor): - 3 months (e.g., surgery, immobilization)

Cancer-Associated: - Lifelong while active cancer - DOAC (Caravaggio, Hokusai-Cancer, SELECT-D) or LMWH

Unprovoked: - 3 months minimum; consider indefinite - HERDOO2 / DASH / Vienna scores to risk-stratify recurrence - DOAC at reduced dose (rivaroxaban 10 mg or apixaban 2.5 mg BID) after initial treatment (AMPLIFY-EXT, EINSTEIN-CHOICE)

Recurrent: - Indefinite

Antiphospholipid Syndrome (APS): - Warfarin (INR 2-3) - Higher INR (2.5-3.5) for arterial events or recurrence - DOAC not preferred (TRAPS, RAPS — increased recurrence)

282.1.0.1.6.3 Massive (High-Risk) PE Treatment

Systemic Thrombolysis: - Alteplase 100 mg IV over 2h OR - Tenecteplase weight-based bolus - Indications: shock, hemodynamic instability - ICH risk ~ 2%, major bleeding 10-15% - MOPETT (half-dose tPA for moderate PE — small trial)

Catheter-Directed Therapy: - Catheter-directed thrombolysis (CDT): lower dose tPA at clot site - Ultrasound-assisted CDT (EkoSonic): SEATTLE II, ULTIMA - Mechanical thrombectomy: - FlowTriever (Inari) — large-bore aspiration; FLARE study - Indigo (Penumbra) — small bore aspiration; EXTRACT-PE - Increasingly favored over systemic lysis (less bleeding) - 2024 ESC: Class IIa with PERT consultation

Surgical Embolectomy: - Rarely; failed lysis or contraindications - Cardiopulmonary bypass

IVC Filter: - Indications: contraindication to anticoagulation; recurrent PE despite therapeutic AC - Retrievable preferred; remove when AC can be initiated - Not for routine adjunct to anticoagulation

282.1.0.1.6.4 ECMO / VA-ECMO

• Bridge for massive PE with refractory shock
• Allows time for thrombolysis or surgery to take effect

282.1.0.1.6.5 PERT (Pulmonary Embolism Response Team)

• Multidisciplinary: cardiology, pulmonology, vascular, interventional radiology, ICU, surgery
• Coordinates complex PE management
• 2024 ESC Class I for severe PE

282.1.0.1.7 Special Populations

282.1.0.1.7.1 Pregnancy

• LMWH preferred (does not cross placenta)
• Switch to UFH around delivery (last 24-48h)
• Continue 6 weeks postpartum minimum
• DOACs not used in pregnancy (cross placenta, fetal effects)

282.1.0.1.7.2 Cancer

• DOAC (apixaban / edoxaban / rivaroxaban) for most
• LMWH for GI/GU cancers (higher bleeding with rivaroxaban/edoxaban)
• Indefinite while cancer active
• Caravaggio, Hokusai-Cancer trials guide

282.1.0.1.7.3 Renal Disease

• Dose-adjust apixaban (5 mg BID if CrCl > 15-25), avoid dabigatran < 30
• UFH for ESRD
• Warfarin OK

282.1.0.1.7.4 HIT (Heparin-Induced Thrombocytopenia)

• IgG against PF4-heparin complex
• 4-T score
• Stop heparin → non-heparin AC (argatroban, bivalirudin, fondaparinux)
• DOAC after platelet recovery

282.1.0.1.8 Chronic Venous Disease (CEAP Classification)

282.1.0.1.8.1 CEAP — Clinical, Etiology, Anatomy, Pathophysiology

Clinical (C): - C0: No signs - C1: Telangiectasias, reticular veins - C2: Varicose veins - C3: Edema - C4a: Pigmentation, eczema - C4b: Lipodermatosclerosis, atrophie blanche - C5: Healed venous ulcer - C6: Active venous ulcer

282.1.0.1.8.2 Pathophysiology

• Venous reflux (incompetent valves) > obstruction
• Venous HTN → leakage → tissue injury
• Long-standing → ulcer formation

282.1.0.1.8.3 Treatment

• Compression therapy (cornerstone): 20-30 mmHg for C2-3; 30-40 for C4-6
• Lifestyle: leg elevation, weight loss, exercise
• Venoactive drugs: micronized purified flavonoid fraction (Daflon), horse chestnut, hesperidin/diosmin
• Sclerotherapy for spider/reticular
• Endovenous thermal ablation (laser, radiofrequency) — gold standard for great saphenous reflux
• Surgical stripping — historical; rarely now
• Wound care for ulcers (compression + dressings, debridement)
• Iliac vein stenting for May-Thurner syndrome or chronic post-thrombotic obstruction

282.1.0.1.9 Post-Thrombotic Syndrome (PTS)

• Chronic venous insufficiency post-DVT
• 30-50% of proximal DVT
• Pain, swelling, hyperpigmentation, ulcers
• Compression stockings + venous interventions
• ATTRACT trial 2017: catheter-directed thrombolysis for acute DVT did NOT prevent PTS overall (but moderate-severe PTS reduced)

282.1.0.2 🩺 床邊速查

• Wells score + D-dimer for DVT and PE
• DVT: compression duplex US
• PE: CTPA (V/Q if contrast CI)
• Massive PE: systemic thrombolysis (alteplase 100 mg or half-dose) or CDT/FlowTriever
• DOAC first-line: apixaban, rivaroxaban (no parenteral lead-in)
• Cancer-VTE: DOAC OK (Caravaggio); LMWH for GI/GU
• APS: warfarin INR 2-3; DOAC NOT preferred (TRAPS)
• Provoked 3 mo, unprovoked ≥ 3 mo + consider indefinite, cancer indefinite

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