Venous Thromboembolism (VTE) — DVT / PE

Symptoms / Associated Sx

  • DVT: Unilateral leg swelling, erythema, warmth, tenderness (calf or thigh); Homan's sign (unreliable)

  • PE: Dyspnea (most common), pleuritic chest pain, tachycardia, hypoxia, cough, hemoptysis

  • Massive PE: Syncope, hypotension, cardiac arrest (obstructive shock)

  • Low-grade fever; elevated JVP, right heart strain signs (massive/submassive PE)

Denies

  • Bilateral leg swelling (rules out DVT as primary — raises heart failure, hypoalbuminemia, bilateral compression)

  • Fever + purulent wound (rules out cellulitis as primary cause of leg erythema/swelling)

  • Pleuritic pain with productive cough + fever + infiltrate (rules out pneumonia as primary)

  • Prior similar episode with negative workup (reduces VTE likelihood)

Social History (SHx)

Recent surgery (especially orthopedic, pelvic, abdominal), immobility, malignancy, prior VTE, oral contraceptives/HRT, pregnancy/postpartum, long-distance travel, hereditary thrombophilia (Factor V Leiden, prothrombin mutation, protein C/S deficiency, antithrombin deficiency), obesity, smoking.

Main Etiology

  • Virchow's triad: stasis (immobility, heart failure) + hypercoagulability (malignancy, thrombophilia, OCP/HRT, pregnancy) + endothelial injury (surgery, trauma, IV catheter)

  • Provoked VTE: surgery, trauma, immobility, malignancy, OCP/HRT, pregnancy

  • Unprovoked VTE: idiopathic or undiagnosed underlying hypercoagulable state or occult malignancy

Most Common DDx

  • Cellulitis (leg erythema + warmth; fever; WBC elevated; bilateral less common; no Doppler thrombus; responds to antibiotics — can coexist with DVT)

  • Musculoskeletal injury — Baker's cyst rupture (posterior knee swelling; US shows cyst rupture not DVT; no anticoagulation needed)

  • Heart failure (bilateral leg edema; elevated BNP; JVD; pulmonary edema on CXR; improves with diuresis)

  • Pneumonia (PE mimic — dyspnea + pleuritic pain; fever + productive cough; consolidation on CXR; no filling defect on CTA; responds to antibiotics)

  • Acute coronary syndrome (PE and ACS both cause chest pain + dyspnea; EKG changes; troponin; echo may help differentiate right heart strain vs. LV dysfunction)

  • Aortic dissection (sudden severe tearing chest/back pain; pulse differential; CT aortography; D-dimer markedly elevated — does not help distinguish from PE)

  • COPD exacerbation / reactive airway disease (dyspnea + hypoxia; wheeze; responds to bronchodilators; CTA may be needed to exclude PE if pre-test probability intermediate-high)

DATA

  • Pre-test probability scoring: Wells score for DVT and PE; PERC rule (if all 8 criteria met → PE excluded without further testing)

  • D-dimer (high sensitivity, low specificity; if low pre-test probability + negative D-dimer → VTE excluded; do not use D-dimer in high pre-test probability — go straight to imaging)

  • Compression ultrasound (CUS) — first-line for DVT; sensitivity ~95% for proximal DVT; lower for distal

  • CT pulmonary angiography (CTPA) — gold standard for PE; first-line if intermediate-high probability or PERC positive

  • V/Q scan — alternative to CTPA if renal insufficiency or contrast allergy; less useful with baseline pulmonary disease

  • EKG (sinus tachycardia most common; S1Q3T3 pattern, new RBBB, T-wave inversions V1–V4 — right heart strain in massive/submassive PE)

  • Troponin + BNP/NT-proBNP (right ventricular injury markers — elevated = submassive/massive PE; prognostic)

  • Echo (RV dilation, RV hypokinesis, D-sign, McConnell's sign — right heart strain in massive PE; valuable for hemodynamically unstable patients)

  • CBC, BMP, coagulation panel (pre-anticoagulation baseline)

  • Thrombophilia workup: factor V Leiden, prothrombin gene mutation, protein C/S, antithrombin III, antiphospholipid antibodies (do NOT test while anticoagulated or acutely — affects results)

  • Age-appropriate malignancy screening if unprovoked VTE (CT chest/abd/pelvis, PSA, mammogram, Pap)

Home Meds

  • Prior anticoagulation (assess compliance and type — therapeutic vs. prophylactic failure)

  • OCP/HRT (hold — thrombogenic; switch contraception)

  • Aspirin / antiplatelets (note — do not rely on aspirin for VTE prevention)

  • Hormone therapy or selective estrogen receptor modulators (tamoxifen, raloxifene — VTE risk)

Plan

  • PE risk stratification:

    • Massive PE (hemodynamic instability — SBP <90 or vasopressors required) → systemic thrombolysis or catheter-directed therapy

    • Submassive PE (hemodynamically stable + RV dysfunction on echo or troponin/BNP elevated) → anticoagulation ± escalation; ICU/step-down monitoring

    • Low-risk PE (PESI class I–II, no RV dysfunction, normal troponin/BNP) → consider outpatient anticoagulation

  • Anticoagulation (first-line for most DVT and non-massive PE):

    • Apixaban (Eliquis) 10 mg PO BID × 7 days → 5 mg PO BID (preferred DOAC — lowest bleeding risk; AMPLIFY trial)

    • Rivaroxaban (Xarelto) 15 mg PO BID × 21 days → 20 mg PO daily with evening meal

    • Dabigatran (Pradaxa) 150 mg PO BID after 5–10 days parenteral anticoagulation

    • Warfarin: bridge with LMWH × 5–7 days until INR 2–3 × 24h; target INR 2–3; less preferred for initial therapy

    • Enoxaparin (LMWH): 1 mg/kg SQ q12h or 1.5 mg/kg SQ daily — use in cancer-associated VTE (preferred over DOACs for most malignancy) or renal failure monitoring situations

    • UFH IV: for massive PE or high bleeding risk requiring rapid reversal; weight-based protocol

  • Massive PE — thrombolysis:

    • Alteplase (tPA) 100 mg IV over 2h (systemic) — if SBP <90 refractory to fluids; high bleeding risk (recent surgery, stroke <3 months = absolute contraindication)

    • Catheter-directed thrombolysis (CDT) or EKOS ultrasound-assisted: submassive or massive PE with contraindications to systemic tPA; IR consult

    • Surgical embolectomy: if tPA contraindicated or failed; cardiac surgery consult

  • Duration of anticoagulation:

    • Provoked (reversible risk factor — surgery/immobility): 3 months

    • Unprovoked first episode: ≥3 months; individualize extended therapy (low bleeding risk → extended anticoagulation reduces recurrence)

    • Cancer-associated VTE: indefinite or until cancer resolved; LMWH or DOACs (apixaban/rivaroxaban preferred for most solid tumor cancers)

    • Recurrent unprovoked VTE: indefinite anticoagulation

    • Antiphospholipid syndrome: indefinite warfarin (INR 2–3); DOACs inferior in APS

  • IVC filter: only if absolute contraindication to anticoagulation AND active bleeding; retrieve when anticoagulation resumes (not permanent unless truly lifelong contraindication)

  • Pulmonary Embolism Response Team (PERT) activation if massive or submassive PE — multidisciplinary

  • Oxygen supplementation; analgesics for pleuritic pain; IV fluids (cautious — RV preload-dependent)

  • Hold OCP/HRT; counsel on VTE prevention strategies

  • Trend CBC, BMP, troponin, BNP; daily if submassive/massive

  • Hematology consult for thrombophilia workup and extended anticoagulation decisions

  • PT/OT; compression stockings for DVT

  • Discharge: DOAC or warfarin with clear duration plan; INR goal and monitoring schedule if warfarin; hold OCP/HRT; malignancy workup if unprovoked; thrombophilia testing 3 months after stopping anticoagulation; hematology follow-up; compression stockings for DVT for symptom management

Red Flags

  • Massive PE (SBP <90, HR >100, syncope, O2 sat <90%) → ICU; systemic tPA vs. CDT vs. surgical embolectomy urgently

  • Cardiac arrest from massive PE → thrombolysis during CPR; extended resuscitation (60–90 min) if tPA given

  • Phlegmasia cerulea dolens (massive DVT with limb ischemia — blue, swollen, painful leg) → systemic tPA or CDT emergently; limb viability threatened

  • PE in pregnancy → LMWH only (DOACs and warfarin contraindicated); CTPA preferred over V/Q if CXR abnormal; IR/MFM consult

  • Heparin-induced thrombocytopenia (HIT) with new DVT/PE → stop all heparin; start argatroban or bivalirudin immediately (see HIT section)

Senior IM Resident Pearls

  • PERC rule: If ALL 8 criteria met (age <50, HR <100, SpO2 ≥95%, no leg swelling, no hemoptysis, no recent surgery/trauma, no prior VTE, no OCP/HRT/estrogen) → PE ruled out without D-dimer in low pre-test probability; do not use if moderate/high pre-test probability

  • Wells PE score: <2 = low probability; 2–6 = moderate; >6 = high — use with D-dimer and CTPA to guide workup

  • S1Q3T3 on EKG is classic but only present in ~10–20% of PE — sinus tachycardia + T-wave inversions V1–V4 is more common and more specific for right heart strain

  • McConnell's sign on echo: RV free wall hypokinesis with preserved RV apex — highly specific for acute PE (but low sensitivity)

  • DOACs are preferred over warfarin for most VTE — no bridging needed, fixed dosing, predictable pharmacokinetics; exception: APS (DOACs inferior — warfarin preferred), pregnancy (LMWH only), mechanical heart valves

  • Common mistake: Ordering D-dimer in a patient with high pre-test probability — D-dimer is a rule-out tool only in low-intermediate probability; in high probability patients, go directly to CTPA regardless of D-dimer result

  • Common mistake: Using systemic tPA for submassive PE routinely — increased bleeding risk; reserve for hemodynamic deterioration; monitor and escalate if RV function worsens

Labs

Admission

  • CBC with diff

  • BMP

  • CMP

  • PT/INR

  • PTT

  • Troponin

  • BNP or NT-proBNP

  • Type & Screen (if high-risk PE)

Additional

  • D-dimer (ONLY if low/intermediate pre-test probability)

  • ABG/VBG (severe hypoxia)

  • Lactate (shock/massive PE)

Trending

  • CBC daily

  • BMP daily

  • Troponin q6–8h (submassive/massive PE)

  • BNP daily (submassive/massive PE)

Imaging

DVT

Venous Duplex Ultrasound

Evaluate:

  • Proximal DVT

  • Distal DVT

  • Clot burden

PE

CT Pulmonary Angiography (CTPA)

First-line diagnostic test

V/Q Scan

If:

  • Contrast allergy

  • Severe CKD

  • Pregnancy consideration

RV Strain Assessment

Echocardiogram

Evaluate:

  • RV dilation

  • RV dysfunction

  • McConnell sign

  • Pulmonary pressures

Additional

EKG

Evaluate:

  • Sinus tachycardia

  • S1Q3T3

  • RV strain

  • New RBBB

CXR

Exclude:

  • Pneumonia

  • CHF

  • Pneumothorax

Procedures

Massive PE

Systemic Thrombolysis

  • Alteplase (tPA) 100 mg IV over 2 hr

Catheter-Directed Thrombolysis (EKOS)

  • IR consult

Surgical Embolectomy

  • Cardiac surgery consult

IVC Filter

Only if:

  • Active VTE

  • Absolute contraindication to anticoagulation

Medications

Anticoagulation (Preferred)

Apixaban

  • 10 mg PO BID x7 days

  • Then 5 mg PO BID

Rivaroxaban

  • 15 mg PO BID x21 days

  • Then 20 mg PO daily

Dabigatran

  • 150 mg PO BID

  • After 5–10 days of heparin

LMWH

Enoxaparin

  • 1 mg/kg SQ q12h

OR

  • 1.5 mg/kg SQ daily

Preferred:

  • Cancer-associated VTE

  • Pregnancy

  • Some CKD patients

Unfractionated Heparin

Heparin Drip

Weight-based protocol

Preferred:

  • Massive PE

  • High bleeding risk

  • Potential procedures

  • Need rapid reversal

Massive PE

Alteplase

  • 100 mg IV over 2 hr

If:

  • SBP <90

  • Obstructive shock

Oxygen

  • Supplemental O2

  • Goal SpO₂ >92%

Pain Control

Acetaminophen

  • 650 mg PO q6h PRN

Oxycodone

  • 2.5–5 mg PO q4–6h PRN

Avoid excessive IV fluids in RV failure.

Hold

  • OCPs

  • HRT

  • Estrogen-containing medications

  • Tamoxifen if possible

Consults

Hematology

  • Unprovoked VTE

  • Recurrent VTE

  • Thrombophilia evaluation

Pulmonology

  • Large PE

  • RV strain

PERT Team

  • Submassive PE

  • Massive PE

Interventional Radiology

  • CDT/EKOS

  • IVC filter

Cardiac Surgery

  • Surgical embolectomy candidate

PT/OT

  • Mobility

  • Deconditioning

Nursing

  • Telemetry

  • Continuous pulse oximetry

  • Fall precautions

  • Ambulation as tolerated

  • Compression stockings (symptom relief)

Notify physician:

  • Hypotension

  • New hypoxia

  • Chest pain

  • Syncope

  • Hemoptysis

Follow-Up

  • CBC daily

  • BMP daily

  • Troponin/BNP trend

  • Monitor oxygen requirements

  • Monitor bleeding

  • Review imaging results

Escalation

Massive PE

Signs:

  • SBP <90

  • Vasopressor requirement

  • Syncope

  • Cardiac arrest

→ ICU
→ tPA
→ PERT
→ IR/Cardiac Surgery

Submassive PE

Signs:

  • Normal BP

  • RV dysfunction

  • Elevated troponin/BNP

→ Stepdown/ICU
→ Echo
→ PERT evaluation

Phlegmasia Cerulea Dolens

Signs:

  • Massive swollen blue leg

  • Limb ischemia

→ Vascular Surgery
→ IR
→ Emergent thrombolysis/thrombectomy

HIT Concern

Signs:

  • Platelets ↓ >50%

  • New thrombosis

→ Stop all heparin

Argatroban

OR

Bivalirudin

Discharge

Anticoagulation Duration

Provoked VTE

  • 3 months

Unprovoked VTE

  • ≥3 months

  • Consider indefinite therapy

Cancer-Associated

  • Indefinite while active cancer

APS

  • Warfarin lifelong

  • INR goal 2–3

Follow-Up

  • Hematology

  • PCP

  • Pulmonology if large PE

Counseling

  • Avoid estrogen-containing medications

  • Early ambulation

  • Compression stockings for DVT symptoms