What is the recommended initial treatment for an adult with acute deep‑vein thrombosis?

Acute Deep Vein Thrombosis Treatment

First-Line Anticoagulation

Start a direct oral anticoagulant (DOAC)—specifically apixaban or rivaroxaban—immediately upon diagnosis, as these agents provide equivalent or superior efficacy to warfarin with better safety and require no parenteral lead-in. 1, 2

DOAC Dosing Regimens

• Rivaroxaban: 15 mg orally twice daily with food for 21 days, then 20 mg once daily with food for the remaining treatment duration 1, 3
• Apixaban: Can be initiated without any preceding parenteral anticoagulation 1
• Edoxaban and dabigatran: Require 5–7 days of parenteral anticoagulation (LMWH, fondaparinux, or unfractionated heparin) before switching to the oral agent 1

When DOACs Are Contraindicated

If DOACs cannot be used (severe renal impairment CrCl <30 mL/min, antiphospholipid syndrome, pregnancy, or patient preference), use the following approach 1, 2:

• LMWH (enoxaparin): 1 mg/kg subcutaneously twice daily OR 1.5 mg/kg once daily 1
• Fondaparinux (weight-based): 5 mg if <50 kg, 7.5 mg if 50–100 kg, 10 mg if >100 kg, subcutaneously once daily 1
• Unfractionated heparin: 80 U/kg IV bolus followed by 18 U/kg/h infusion, titrated to aPTT 1.5–2.5 × control 1

Warfarin Bridging Protocol

• Start warfarin on day 1 simultaneously with parenteral anticoagulation 1, 2
• Continue parenteral therapy for minimum 5 days AND until INR ≥2.0 for ≥24 hours 1, 2
• Target INR 2.0–3.0 (optimal 2.5) throughout treatment 1, 2

Treatment Duration Algorithm

Stop at 3 Months

• Provoked DVT with major transient risk factor (surgery, major trauma, hospitalization): Discontinue anticoagulation exactly at 3 months; annual recurrence risk after stopping is <1% 1, 2
• Provoked DVT with minor transient risk factor (estrogen therapy, prolonged travel, minor injury): Stop at 3 months in most patients 1, 2

Continue Indefinitely

• Unprovoked DVT with low-to-moderate bleeding risk: Extend anticoagulation indefinitely because annual recurrence risk after stopping exceeds 5%, outweighing bleeding risk 1, 2
• DVT with persistent risk factor (active cancer, chronic immobility, antiphospholipid syndrome): Indefinite anticoagulation required 1, 2
• Second unprovoked DVT: Lifelong anticoagulation mandatory regardless of bleeding risk 1, 2
• Reassess risk-benefit balance at least annually 1, 2

Treatment Setting and Mobilization

• Manage at home rather than hospitalize when the patient has stable living conditions, adequate support, and rapid access to care 1
• Encourage early ambulation immediately after anticoagulation initiation; bed rest does not reduce pulmonary embolism risk and may worsen outcomes 1
• Apply 30–40 mmHg knee-high compression stockings during mobilization to reduce acute symptoms and prevent post-thrombotic syndrome 1

Special Populations

Cancer-Associated DVT

• Oral factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) are now preferred over LMWH 1, 2
• In patients with luminal gastrointestinal malignancies, avoid edoxaban and rivaroxaban; use apixaban or LMWH instead due to higher GI bleeding risk 1
• Continue anticoagulation indefinitely while malignancy or chemotherapy remains active 1

Antiphospholipid Syndrome

• Adjusted-dose warfarin (target INR 2.5) is preferred over DOACs because DOACs increase recurrent thrombosis risk in this population 1, 2
• Overlap with parenteral anticoagulation during warfarin initiation 1

Severe Renal Impairment (CrCl <30 mL/min)

• Unfractionated heparin is the preferred initial anticoagulant: 80 U/kg IV bolus followed by 18 U/kg/h infusion, adjusted by aPTT monitoring 2
• Warfarin is the long-term anticoagulant of choice with target INR 2.0–3.0 2
• LMWH, fondaparinux, and all DOACs must be avoided due to renal elimination and accumulation risk 2

Isolated Distal (Calf) DVT

• Without severe symptoms or high-risk features: Perform serial duplex ultrasound every 2 weeks for 2 weeks rather than immediate anticoagulation 1, 2
• If thrombus extends distally: Initiate anticoagulation 1
• If thrombus extends proximally: Anticoagulation is mandatory 1
• With severe symptoms or high-risk features (active cancer, prior VTE, extensive clot burden): Immediate anticoagulation required 2
• When anticoagulation is started, treat for 3 months—same duration as proximal DVT 2

Interventions to Avoid

• Do not use catheter-directed thrombolysis, systemic thrombolysis, or surgical thrombectomy routinely; 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 and low bleeding risk 1, 2
• Do not place IVC filters routinely; they are indicated exclusively for patients with absolute contraindications to anticoagulation (active major bleeding, recent neurosurgery) 1, 2
• If a temporary filter is placed, restart anticoagulation as soon as bleeding risk resolves 1

Critical Pitfalls to Avoid

• Never discontinue anticoagulation before 3 months for any acute DVT; early cessation markedly increases recurrence and extension risk 1, 2
• Never prescribe DOACs in confirmed antiphospholipid syndrome; use adjusted-dose warfarin instead 1, 2
• Never use LMWH or fondaparinux in CrCl <30 mL/min due to drug accumulation and major bleeding risk 2
• Never enforce prolonged bed rest based on outdated embolization concerns; early ambulation is safe and beneficial 1
• Never hospitalize patients unnecessarily; home treatment is safe and preferred when circumstances allow 1
• Never use warfarin as first-line therapy when DOACs are available and not contraindicated 1

Monitoring Requirements

• Warfarin therapy: Regular INR measurements targeting 2.0–3.0 1
• DOAC therapy: Routine laboratory monitoring is not required 1
• Unfractionated heparin: Check aPTT every 6 hours initially to maintain 1.5–2.5 × control 2