What vitamin K antagonists are recommended for the treatment of Budd-Chiari syndrome?

Vitamin K Antagonists for Budd-Chiari Syndrome

Warfarin, acenocoumarol, and phenprocoumon are the recommended vitamin K antagonists for long-term anticoagulation in Budd-Chiari syndrome, with warfarin being the most commonly used agent targeting an INR of 2.0-3.0. 1

Specific VKA Agents

The vitamin K antagonists used in clinical practice include:

• Warfarin - the most widely prescribed VKA globally and the predominant agent used in BCS management 2, 1
• Acenocoumarol - commonly used in Europe as an alternative to warfarin 2
• Phenprocoumon - another European VKA option with a longer half-life 2
• Phenindione and fluindione - less commonly prescribed VKAs that remain available 2

Treatment Protocol for BCS

Initial anticoagulation should begin with low molecular weight heparin (LMWH) for 5-7 days, followed by transition to oral VKA therapy targeting an INR of 2.0-3.0, which must be continued indefinitely. 1

Initiation Strategy

• Start LMWH immediately upon diagnosis of BCS 1, 3
• Overlap VKA with parenteral anticoagulation for at least 5 days 2
• Continue parenteral therapy until INR has been 2.0-3.0 for two consecutive days 2
• For warfarin specifically: start with 10 mg daily in younger patients (<60 years) who are otherwise healthy, or 5 mg daily in older or hospitalized patients 2

Monitoring Requirements

• Check INR at least weekly during initiation phase 2
• Once stable, INR testing can be extended to monthly intervals 2
• For patients with consistently stable INRs, testing frequency can be extended up to 12 weeks rather than every 4 weeks 2

Critical Contraindications

Vitamin K antagonists are absolutely contraindicated during pregnancy due to risk of fetal hemorrhage and teratogenicity. 2

• LMWH is the anticoagulant of choice during pregnancy for women with BCS 2
• VKAs are acceptable during breastfeeding 2

Bleeding Risk Considerations

Patients with mutations in CYP2C9 and/or VKORC1 genes have a 3-fold higher risk of bleeding complications on warfarin (crude OR 3.13,95% CI 1.1-8.9) and require more intensive INR monitoring. 4

• Bleeding complications on anticoagulation have decreased from 50% in older studies to 17% in recent data due to better procedural management and adequate portal hypertension prophylaxis 1
• Portal hypertension complications (varices, ascites), when adequately treated, are NOT contraindications to anticoagulation 1

Reversal When Needed

If urgent reversal of VKA is required (e.g., for intracranial hemorrhage):

• Administer vitamin K 10 mg IV immediately 2
• Give 3-factor or 4-factor prothrombin complex concentrate (PCC) based on weight and INR 2, 5:
  • INR 2 to <4: 25 units/kg
  • INR 4-6: 35 units/kg
  • INR >6: 50 units/kg
• If INR remains elevated ≥1.4 within 24-48 hours, redose vitamin K 10 mg IV 2

Emerging Alternative: Direct Oral Anticoagulants

While VKAs remain the guideline-recommended standard, recent evidence suggests DOACs may be effective alternatives:

• A multicenter Austrian study showed DOACs (edoxaban, apixaban, rivaroxaban, dabigatran) achieved complete response in 63.6% of BCS patients with transplant-free survival of 91.6% at 5 years 6
• Major bleeding rate was 18.2% (8.8 per 100 patient-years) on DOACs 6
• However, DOACs remain off-label for BCS and require confirmation by larger prospective studies before they can be recommended over VKAs 6

Common Pitfalls to Avoid

• Do not delay anticoagulation initiation while awaiting complete thrombophilia workup 1
• Do not discontinue anticoagulation after interventional procedures (TIPS, angioplasty); lifelong therapy is required 1
• Do not use INR values alone to guide DOAC reversal if a patient is switched from VKA, as INR does not reliably reflect DOAC activity 5
• Do not assume normal blood counts exclude myeloproliferative neoplasm; 71% of BCS patients have MPN, including some with normal counts at diagnosis 3