What is the primary cause of Budd Chiari syndrome?

Etiology of Budd-Chiari Syndrome

Myeloproliferative neoplasms are the most common cause of Budd-Chiari syndrome, accounting for approximately 50% of cases in Western countries. 1, 2, 3

Primary Causes of Budd-Chiari Syndrome

Budd-Chiari syndrome (BCS) is defined as obstruction of hepatic venous outflow that can be located from small hepatic venules up to the entrance of the inferior vena cava (IVC) into the right atrium, excluding cardiac disease, pericardial disease, or sinusoidal obstruction syndrome 1.

Prothrombotic Conditions (Most Common)

1. Myeloproliferative Neoplasms (MPNs)

   • Present in approximately 40-50% of BCS patients 2, 3
   • Often diagnosed by testing for JAK2V617F mutation in peripheral blood granulocytes 1
   • If JAK2V617F negative, calreticulin mutation screening should be performed 1
   • MPNs in BCS often have atypical presentation with normal blood counts 4

2. Inherited Thrombophilias

   • Factor V Leiden mutation (accounts for 25% of cases) 1
   • Protein C deficiency
   • Protein S deficiency
   • Antithrombin deficiency
   • Prothrombin G20210A gene variant 1

3. Acquired Thrombophilias

   • Antiphospholipid syndrome 1
   • Paroxysmal nocturnal hemoglobinuria 1, 2
   • Oral contraceptive use

4. Autoimmune Disorders 1, 2

Important Clinical Considerations

• Multiple risk factors are often combined in the same patient 3, 4
• In Western countries, pure hepatic vein thrombosis is most common 1
• In Asian countries, IVC obstruction or combined IVC/hepatic vein block predominates 1, 5
• Approximately 10% of cases are caused by malignancies through compression or direct invasion of hepatic veins or vena cava 1

Diagnostic Approach

1. Initial Imaging

   • Doppler ultrasound (sensitivity >75%) is the first-line investigation 1, 2
   • If inconclusive, proceed to MRI or CT evaluation 1, 2
   • Venography is recommended if diagnosis remains uncertain 1

2. Thrombophilia Screening

   • Test for protein S, protein C and antithrombin levels
   • Factor V Leiden mutation
   • Prothrombin G20210A gene variant
   • Antiphospholipid antibodies (repeat after 12 weeks if positive) 1

3. Myeloproliferative Neoplasm Testing

   • JAK2V617F mutation testing (even with normal blood counts) 1, 2
   • If negative, test for calreticulin mutation
   • If both negative, consider bone marrow histology 1
   • Refer to hematologist for management 1

4. Additional Investigations

   • Screen for local risk factors including intra-abdominal inflammatory conditions and abdominal malignancies 1

Clinical Implications

The etiology of BCS significantly impacts treatment approach and prognosis:

• Patients with underlying MPNs require indefinite anticoagulation 1, 2
• Patients with malignancy-related BCS and those with combined hepatic and portal vein thrombosis have worse outcomes 1
• Treatment of the underlying prothrombotic cause, especially MPNs, should be initiated concurrently with anticoagulation 2

Common Pitfalls

1. Failure to perform comprehensive thrombophilia screening - Multiple risk factors are often present in the same patient
2. Missing MPNs with normal blood counts - JAK2V617F testing is essential even with normal peripheral blood counts
3. Delayed diagnosis - Consider BCS in any patient with unexplained ascites, hepatomegaly, and signs of portal hypertension
4. Inadequate follow-up - Long-term monitoring is essential as underlying conditions may transform or hepatocellular carcinoma may develop 3, 4

The identification of the underlying etiology is crucial for appropriate management and long-term prognosis of patients with Budd-Chiari syndrome.