What is the recommended treatment for an acute deep‑vein thrombosis in an adult without contraindications?

Treatment of Acute Deep Vein Thrombosis

First-Line Anticoagulation Strategy

Start a direct oral anticoagulant (DOAC)—specifically apixaban or rivaroxaban—immediately upon diagnostic confirmation; these agents are strongly preferred over warfarin because they require no parenteral bridging, demonstrate superior safety, and provide at least equivalent efficacy. 1

• Apixaban dosing: 10 mg orally twice daily for 7 days, then 5 mg twice daily for the remainder of treatment. 2
• Rivaroxaban dosing: 15 mg orally twice daily with food for 21 days, then 20 mg once daily with food. 1
• Apixaban and rivaroxaban eliminate the need for initial heparin or LMWH, enabling immediate outpatient management and simplifying care. 1
• Edoxaban requires 5–10 days of parenteral anticoagulation (LMWH, fondaparinux, or unfractionated heparin) before starting 60 mg once daily (or 30 mg daily if creatinine clearance 30–50 mL/min or weight <60 kg). 2
• Dabigatran requires at least 5 days of parenteral anticoagulation before starting 150 mg orally twice daily. 2, 3

When DOACs Cannot Be Used

If a DOAC is contraindicated (severe renal impairment with CrCl <30 mL/min, confirmed antiphospholipid syndrome, pregnancy, or mechanical heart valves), initiate low-molecular-weight heparin or fondaparinux immediately and overlap with warfarin starting on day 1. 1

• LMWH dosing: Enoxaparin 1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg once daily; Dalteparin 200 units/kg subcutaneously once daily. 2
• Fondaparinux dosing (weight-based): 5 mg if <50 kg, 7.5 mg if 50–100 kg, 10 mg if >100 kg, administered subcutaneously once daily. 2
• Unfractionated heparin dosing: 80 units/kg IV bolus followed by 18 units/kg/hour continuous infusion, adjusted to maintain aPTT 1.5–2.5 times control. 2
• Warfarin initiation: Start 2.5–5 mg daily on day 1 concurrently with parenteral therapy; continue the parenteral agent for at least 5 days and until the INR is ≥2.0 for a minimum of 24 hours. 2, 1
• Target INR: 2.5 (therapeutic range 2.0–3.0) for the entire treatment course. 2, 1

Minimum Treatment Duration

All patients with acute DVT require at least 3 months of therapeutic anticoagulation regardless of provocation status; stopping earlier markedly increases recurrence and extension risk. 1, 4

Duration Decision Algorithm at 3 Months

Stop Anticoagulation at 3 Months

• Provoked DVT with a major transient risk factor (recent major surgery, major trauma, hospitalization, prolonged immobilization): annual recurrence risk after stopping is <1%; discontinue anticoagulation exactly at 3 months because extending therapy provides no additional benefit. 1, 4
• Provoked DVT with a minor transient risk factor (estrogen therapy, prolonged travel >8 hours, minor injury, minor surgery): annual recurrence risk 3–5%; stop at 3 months in most patients, extending only if bleeding risk is exceptionally low. 1

Continue Indefinitely (No Scheduled Stop Date)

• Unprovoked DVT with low-to-moderate bleeding risk: annual recurrence risk exceeds 5–10%; offer indefinite extended-phase anticoagulation with a DOAC because the benefit of preventing recurrence outweighs bleeding risk. 1, 4
• Persistent risk factors (active cancer, chronic immobility, antiphospholipid syndrome, inherited thrombophilia): indefinite anticoagulation is mandatory as long as the risk factor persists. 1
• Second unprovoked DVT: lifelong anticoagulation is required irrespective of bleeding risk. 1
• Reassess the risk-benefit balance at least annually and after any major change in health status (new cancer diagnosis, major bleeding event, falls, cognitive decline). 1, 4

Special Populations

Cancer-Associated DVT

• Oral factor Xa inhibitors (apixaban, rivaroxaban, or edoxaban) are preferred over LMWH for cancer-associated DVT based on moderate-certainty evidence showing equivalent efficacy with improved convenience. 2, 1
• Avoid edoxaban or rivaroxaban in patients with luminal gastrointestinal malignancies (esophageal, gastric, colorectal) due to higher GI bleeding risk; use apixaban or LMWH instead. 2, 1
• Anticoagulation should be continued for at least 3–6 months and extended indefinitely as long as the malignancy or chemotherapy remains active. 1

Antiphospholipid Syndrome

• Use adjusted-dose warfarin (target INR 2.5) instead of DOACs because DOACs increase the risk of recurrent thrombosis in confirmed antiphospholipid syndrome. 2, 1
• Overlap warfarin with parenteral anticoagulation during initiation. 1

Severe Renal Impairment (CrCl <30 mL/min)

• Unfractionated heparin is the preferred initial anticoagulant because it is cleared hepatically, has a short half-life, and can be reversed with protamine sulfate. 1
• LMWH and fondaparinux must be avoided because renal elimination leads to drug accumulation and markedly increased bleeding risk. 1
• Warfarin is the preferred long-term anticoagulant for this population; DOACs are contraindicated or should be avoided. 1

Isolated Distal (Calf) DVT

• In patients without severe symptoms or high-risk features (no active cancer, prior VTE, or extensive clot burden), perform serial duplex ultrasound every 2 weeks for 2 weeks instead of immediate anticoagulation. 1, 4
• If repeat imaging shows proximal extension, anticoagulation becomes mandatory. 1
• If only distal extension is seen, initiate anticoagulation. 1
• Patients with severe symptoms or high-risk features (active cancer, prior VTE, extensive clot burden) should receive immediate anticoagulation. 1
• When anticoagulation is started for distal DVT, treat for 3 months—the same duration as for proximal DVT. 1, 4

Treatment Setting and Mobilization

• Manage most patients with uncomplicated DVT at home rather than hospitalizing them, provided they have stable living conditions, adequate support, and rapid access to care if deterioration occurs. 1, 4
• Encourage early ambulation immediately after anticoagulation initiation; prolonged bed rest does not reduce pulmonary embolism risk and may worsen outcomes by increasing thrombotic complications. 1, 4
• Apply 30–40 mm Hg knee-high compression stockings during mobilization to reduce acute symptoms and prevent post-thrombotic syndrome; continue for at least 2 years. 4

Interventions to Avoid

• Do not use catheter-directed thrombolysis, systemic thrombolysis, or operative venous thrombectomy for routine DVT; anticoagulation alone is sufficient. 1, 4
• Reserve thrombolytic therapy only for limb-threatening circulatory compromise (phlegmasia cerulea dolens) or selected young patients with acute iliofemoral DVT who have severe symptoms and low bleeding risk. 1
• Do not place an IVC filter in addition to anticoagulation for routine DVT management; filters are indicated exclusively for patients with absolute contraindications to anticoagulation (active major bleeding, recent neurosurgery, unrecoverable bleeding risk). 1, 4
• If a temporary filter is placed, restart anticoagulation as soon as the bleeding risk resolves and arrange prompt filter removal. 1

Critical Pitfalls to Avoid

• Never discontinue anticoagulation before completing 3 months for any acute DVT; early cessation markedly raises recurrence and extension risk. 1, 4
• Never prescribe DOACs in confirmed antiphospholipid syndrome; use adjusted-dose warfarin (target INR 2.5) instead. 2, 1
• Never place IVC filters routinely; they do not reduce mortality, increase long-term DVT risk, and are indicated only when anticoagulation cannot be administered. 1, 4
• Never enforce prolonged bed rest based on outdated concerns about embolization; early ambulation is safe and beneficial. 1, 4
• Never stop parenteral anticoagulation before achieving a therapeutic INR (≥2.0 for ≥24 hours) when transitioning to warfarin. 2, 1
• Never use LMWH or fondaparinux in patients with severe renal impairment (CrCl <30 mL/min) because of drug accumulation and major bleeding risk. 1
• Never use warfarin as first-line therapy when DOACs are available and not contraindicated; DOACs have superior safety and equivalent efficacy. 1, 4

Monitoring Requirements

• Warfarin therapy: Check INR within 1–2 weeks after any dose adjustment and maintain the target range 2.0–3.0; once stable, monitor every 2–4 weeks. 1
• DOAC therapy: Routine laboratory monitoring is not required. 1
• Unfractionated heparin: Check aPTT every 6 hours initially to maintain therapeutic range 1.5–2.5 times control. 1