Cardiovascular · PANCE / PANRE

Deep Vein Thrombosis (DVT)

Thrombus in the deep venous system, most often lower extremity — risk-stratify with Wells, confirm with duplex US, treat with anticoagulation.

Also known as: DVT, deep vein thrombosis, venous thromboembolism, VTE, lower extremity thrombosis

Overview

Formation of thrombus within the deep venous system, most commonly involving lower extremity veins (popliteal, femoral, iliac). Proximal DVT (popliteal or above) carries the highest risk of pulmonary embolism; distal (calf) DVT is generally lower risk.

Epidemiology

Annual incidence of venous thromboembolism ~1-2 per 1000. Together with PE, VTE is the third most common cardiovascular cause of death. Up to half are provoked by identifiable risk factors; the remainder unprovoked.

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Risk factors

  • Virchow triad: venous stasis, endothelial injury, hypercoagulability
  • Surgery (especially orthopedic — hip, knee, pelvic; total joint replacement carries highest risk)
  • Trauma, immobilization (hospitalization, casting, long-haul travel)
  • Active malignancy (especially pancreatic, gastric, ovarian, brain — Trousseau syndrome)
  • Pregnancy and 6-week postpartum period
  • Oral contraceptives, hormone replacement therapy, tamoxifen
  • Inherited thrombophilia: Factor V Leiden, prothrombin G20210A, protein C/S/antithrombin deficiency
  • Antiphospholipid antibody syndrome
  • Obesity, age >60, smoking
  • Prior VTE (strongest single risk factor for recurrence)
  • Central venous catheter, indwelling hardware

Pathophysiology

Stasis in venous valve cusps combined with hypercoagulable state initiates thrombus formation. The thrombus may extend proximally or embolize to the pulmonary circulation. Chronic venous outflow obstruction and valvular damage lead to post-thrombotic syndrome.

Clinical presentation

Symptoms

  • Unilateral leg swelling and pain (most common)
  • Calf or thigh discomfort, often worse with walking
  • Warmth, erythema
  • Asymptomatic in many cases — first manifestation may be pulmonary embolism
  • Phlegmasia cerulea dolens (rare, limb-threatening): severe swelling, cyanosis, pain from massive iliofemoral thrombus

Signs / physical exam

  • Unilateral leg swelling >3 cm calf circumference difference (measured 10 cm below tibial tuberosity)
  • Pitting edema, palpable cord
  • Erythema, warmth
  • Homan sign (calf pain with dorsiflexion) — historical, low sensitivity/specificity
  • Tachycardia, hypoxia if concurrent PE

Differential diagnosis

  • Cellulitis — Erythema with sharp borders, fever, leukocytosis; warmth without palpable cord; negative duplex
  • Ruptured Baker cyst — Sudden calf pain with cyst rupture; ultrasound shows fluid tracking down calf without venous thrombus
  • Muscle strain or hematoma — Trauma history, localized tenderness; negative duplex
  • Chronic venous insufficiency / superficial thrombophlebitis — Palpable cord along superficial vein; tender erythematous track; treated with NSAIDs ± anticoagulation if extensive
  • Lymphedema — Chronic non-pitting edema with skin changes; bilateral or asymmetric without acute pain
  • Compartment syndrome — Pain out of proportion, paresthesia, post-trauma or post-exercise; emergent surgical consult
  • Heart failure — Bilateral pitting edema with dyspnea, elevated JVP, pulmonary congestion

Diagnostic workup

Diagnostic criteria

Wells DVT score: each +1 for active cancer, paralysis/immobilization, recent surgery, localized tenderness along deep veins, entire leg swelling, calf >3 cm difference, pitting edema, collateral superficial veins, prior DVT; subtract 2 if alternative diagnosis as likely. Score ≥2 = likely; <2 = unlikely. Unlikely + negative D-dimer rules out; likely or positive D-dimer warrants duplex.

Labs

  • D-dimer — sensitive but nonspecific; useful in low-pretest-probability patients to exclude DVT
  • CBC, BMP, coagulation studies, hepatic function (drug dosing)
  • Pregnancy test in women of childbearing age
  • Selective thrombophilia workup (Factor V Leiden, prothrombin G20210A, protein C/S, antithrombin, antiphospholipid antibodies) — in young unprovoked DVT, recurrent VTE, or strong family history; defer testing until off anticoagulation when possible
  • Age-appropriate cancer screening for unprovoked VTE — no aggressive occult malignancy workup unless symptoms or signs

Imaging

  • Compression duplex ultrasound — first-line; sensitivity and specificity >95% for proximal DVT
  • CT or MR venography for proximal pelvic veins or IVC when duplex limited
  • Echocardiography and CTPA if PE suspected concurrently
  • Wells criteria for clinical pretest probability — drives D-dimer vs imaging decision

Diagnostic algorithm

flowchart TD
  A[Suspected DVT] --> B[Wells DVT score]
  B --> C{Score}
  C -->|Unlikely <2| D[D-dimer]
  D --> E{D-dimer<br/>elevated?}
  E -->|No| F[DVT excluded]
  E -->|Yes| G[Compression duplex US]
  C -->|Likely ≥2| G
  G --> H{Thrombus<br/>identified?}
  H -->|No| I[Consider alternate dx<br/>or repeat US in 5-7 days<br/>if high suspicion]
  H -->|Yes| J[Anticoagulate: DOAC preferred<br/>LMWH for pregnancy/cancer<br/>Warfarin if specific indication]
  J --> K{Provoked vs<br/>unprovoked?}
  K -->|Provoked| L[3 months therapy]
  K -->|Unprovoked / recurrent /<br/>persistent risk| M[Consider indefinite therapy<br/>based on bleeding risk]
Diagnostic and treatment algorithm for suspected lower extremity DVT.

Treatment

First-line

  • Anticoagulation — direct oral anticoagulants (DOACs) preferred for most acute VTE in absence of contraindications:
  • • Apixaban 10 mg PO BID × 7 days then 5 mg BID
  • • Rivaroxaban 15 mg PO BID × 21 days then 20 mg daily with food
  • • Edoxaban — requires 5-10 day bridge with parenteral anticoagulation first
  • • Dabigatran — requires 5-10 day bridge with parenteral anticoagulation first
  • Low-molecular-weight heparin (enoxaparin 1 mg/kg SC q12h) — preferred in pregnancy, active cancer (especially GI malignancy where DOACs have higher bleeding), severe renal impairment may use IV unfractionated heparin
  • Warfarin with parenteral bridging (target INR 2-3) — for patients on warfarin already, mechanical heart valves, certain APS, or DOAC intolerance
  • Duration: 3 months minimum for provoked DVT; indefinite for unprovoked proximal DVT or PE with low bleeding risk, recurrent VTE, or persistent risk factor

Second-line / adjunct

  • IVC filter — only for acute VTE with absolute contraindication to anticoagulation, or recurrent VTE despite therapeutic anticoagulation; retrievable filters preferred and should be removed when anticoagulation can resume
  • Catheter-directed thrombolysis or thrombectomy — for limb-threatening iliofemoral DVT (phlegmasia) or selected young patients with extensive proximal DVT to reduce post-thrombotic syndrome
  • Compression stockings (20-30 mmHg) for symptomatic relief; routine use no longer recommended solely to prevent post-thrombotic syndrome (SOX trial)
  • Address modifiable risk factors: stop estrogen-containing contraceptives, treat malignancy, weight management
  • Hospitalize if extensive DVT, suspected concurrent PE, hemodynamic compromise, high bleeding risk, or limited social support

Complications

  • Pulmonary embolism (the dreaded complication; can be fatal)
  • Post-thrombotic syndrome — chronic pain, edema, hyperpigmentation, venous ulceration
  • Chronic thromboembolic pulmonary hypertension
  • Recurrent VTE
  • Anticoagulation-related bleeding (intracranial, GI)
  • Phlegmasia cerulea dolens with limb loss

PANCE pearls

  • Wells score with negative D-dimer reliably rules out DVT in low-risk outpatients — saves imaging.
  • DOACs are first-line for most VTE; LMWH still preferred in pregnancy and many GI malignancies.
  • Unprovoked proximal DVT or PE → consider indefinite anticoagulation given high recurrence risk.
  • Stop estrogen-containing contraceptives in any patient diagnosed with VTE on hormonal therapy.
  • IVC filters are reserved for those who CANNOT be anticoagulated — they do not replace anticoagulation when it can be given.

References

  • CHEST 2021 VTE — Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report (Stevens et al., Chest 2021)
  • ASH 2020 VTE — American Society of Hematology 2020 Guidelines for Management of Venous Thromboembolism (Ortel et al., Blood Adv 2020)
  • AMPLIFY — Oral Apixaban for the Treatment of Acute Venous Thromboembolism (Agnelli et al., NEJM 2013)
  • EINSTEIN-DVT — Oral Rivaroxaban for Symptomatic Venous Thromboembolism (EINSTEIN Investigators, NEJM 2010)
  • SOX Trial — Compression Stockings to Prevent Post-Thrombotic Syndrome (Kahn et al., Lancet 2014)

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