What is the recommended first‑line anticoagulation regimen and duration for an adult with an acute deep‑vein thrombosis who has no absolute contraindications to anticoagulation?

First-Line Anticoagulation for Acute Deep Vein Thrombosis

For an adult with acute DVT and no contraindications to anticoagulation, initiate a direct oral anticoagulant (DOAC)—specifically apixaban or rivaroxaban—as first-line therapy, and continue anticoagulation for a minimum of 3 months, with the decision to extend indefinitely based on whether the DVT was provoked or unprovoked. 1, 2

Preferred Anticoagulation Regimen

First-Line: Direct Oral Anticoagulants (DOACs)

• Apixaban or rivaroxaban are the preferred agents because they can be started immediately without requiring initial parenteral anticoagulation (no "bridge" therapy needed), have equivalent or superior efficacy to warfarin, lower bleeding risk, and greater convenience. 1, 2

• 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 thereafter. 2, 3

• Edoxaban and dabigatran are acceptable alternatives but require 5–10 days of parenteral anticoagulation (LMWH, fondaparinux, or unfractionated heparin) before switching to the oral agent, making them less convenient. 1, 2, 3

Alternative: Parenteral Anticoagulation Bridged to Warfarin

• If DOACs are contraindicated (severe renal impairment with CrCl <30 mL/min, pregnancy, antiphospholipid syndrome, or patient preference), use low-molecular-weight heparin (LMWH) as the preferred parenteral agent. 1, 2

• LMWH dosing: Enoxaparin 1 mg/kg subcutaneously twice daily OR 1.5 mg/kg once daily. 1, 2

• Fondaparinux dosing (weight-based): 5 mg if <50 kg, 7.5 mg if 50–100 kg, 10 mg if >100 kg, all given subcutaneously once daily. 1, 2

• Unfractionated heparin dosing: 80 U/kg IV bolus followed by 18 U/kg/hour continuous infusion, adjusted to maintain aPTT 1.5–2.5 times control. 1, 2

• Warfarin should be started on day 1 simultaneously with parenteral therapy, continued for a minimum of 5 days and until INR ≥2.0 for at least 24 hours, with a target therapeutic INR of 2.0–3.0 (optimal target 2.5). 1, 4, 5, 2

Duration of Anticoagulation

Provoked DVT (Major Transient Risk Factor)

• Treat for exactly 3 months, then stop anticoagulation. 1, 2

• This applies when DVT occurred in the setting of major surgery, major trauma, or other clearly identifiable temporary risk factors; extending therapy beyond 3 months provides no additional benefit. 1, 2

Provoked DVT (Minor Transient Risk Factor)

• Treat for 3 months, then stop anticoagulation. 1

Unprovoked DVT or DVT with Persistent Risk Factor

• Provide a minimum of 3 months of initial therapy, then extend anticoagulation indefinitely (no scheduled stop date) for patients with low-to-moderate bleeding risk. 1, 2

• After the initial 3 months, reassess the risk-benefit balance at least annually; trial data support extended treatment durations of 2–4 years. 1, 2

• The decision to extend indefinitely is strengthened if the patient is male, the index event was PE rather than isolated DVT, and/or D-dimer testing is positive 1 month after stopping anticoagulation. 6

Cancer-Associated DVT

• Oral factor Xa inhibitors (apixaban, edoxaban, or rivaroxaban) are now preferred over LMWH for cancer-associated DVT. 1, 2

• In patients with luminal gastrointestinal malignancies, apixaban or LMWH should be used instead of edoxaban or rivaroxaban due to higher GI bleeding risk with the latter agents. 2, 7

• Anticoagulation should be continued for at least 3–6 months and extended indefinitely (no scheduled stop date) as long as the malignancy or chemotherapy remains active. 1, 4, 5, 2

Recurrent Unprovoked DVT

• Indefinite anticoagulation is recommended. 5, 2

Treatment Setting and Mobilization

• Most patients with uncomplicated DVT should be treated at home rather than hospitalized, provided home circumstances are adequate (stable living conditions, support, phone access) and the patient can return quickly if deterioration occurs. 1, 2

• Encourage early ambulation immediately after anticoagulation initiation; mobilization does not increase pulmonary embolism risk and may improve outcomes. 1, 2

• Apply 30–40 mm Hg knee-high compression stockings during early mobilization to reduce acute symptoms and prevent post-thrombotic syndrome; continue for at least 2 years after the DVT event. 4, 2

Special Populations

Antiphospholipid Syndrome

• Adjusted-dose warfarin (target INR 2.0–3.0, optimal 2.5) is preferred over DOACs, with overlapping parenteral anticoagulation during warfarin initiation. 1, 2

Heparin-Induced Thrombocytopenia

• Treat with intravenous direct thrombin inhibitors (argatroban or lepirudin). 5, 2

Renal Impairment

• Avoid or dose-adjust LMWH in patients with CrCl <30 mL/min; unfractionated heparin is the preferred alternative. 5

Interventions to Avoid in Routine DVT Management

• Do not use catheter-directed thrombolysis, pharmacomechanical thrombectomy, systemic thrombolysis, or surgical venous thrombectomy for routine DVT; anticoagulation alone is sufficient. 1, 2

• Reserve thrombolysis only for limb-threatening circulatory compromise (phlegmasia cerulea dolens) or selected young patients with acute iliofemoral DVT who have severe symptoms, low bleeding risk, and access to catheter-directed therapy. 1, 2

• Do not place an inferior vena cava (IVC) filter in addition to anticoagulation for routine DVT; IVC filters are reserved exclusively for patients with absolute contraindications to anticoagulation. 1, 2

Management of Isolated Distal (Calf) DVT

• When the distal DVT is uncomplicated (no severe symptoms or extension risk factors), perform serial duplex imaging for 2 weeks instead of immediate anticoagulation. 2

• If the thrombus does not extend, anticoagulation can be omitted; if it extends but remains distal, consider anticoagulation; if it extends proximally, manage as a proximal DVT with full anticoagulation. 2

• If the distal DVT is associated with severe symptoms or risk factors for extension, initiate anticoagulation immediately using the same regimen as for proximal DVT. 2

Monitoring Requirements

• Warfarin therapy requires regular INR measurements aiming for a therapeutic range of 2.0–3.0. 1, 4, 5, 2

• DOAC therapy does not require routine laboratory monitoring. 5, 2

Common Pitfalls to Avoid

• Do not enforce bed rest based on outdated concerns about embolization; early ambulation is safe and beneficial. 2

• Do not hospitalize patients unnecessarily; home treatment is safe and preferred when circumstances allow. 2

• Do not use warfarin as first-line therapy when DOACs are available and not contraindicated. 2

• Do not stop anticoagulation prematurely in unprovoked DVT; these patients typically require extended therapy. 2

• Do not fail to bridge with LMWH when INR falls below therapeutic range in a patient with recent DVT. 4