Most Common Myeloproliferative Neoplasms in Budd-Chiari Syndrome
Polycythemia vera and essential thrombocythemia are the most common myeloproliferative neoplasms associated with Budd-Chiari syndrome, with polycythemia vera being particularly predominant. 1
Prevalence and Specific MPN Subtypes
Myeloproliferative disorders represent the most common underlying cause of Budd-Chiari syndrome, accounting for approximately 40-49% of all cases 1, 2, 3. Among the specific MPN subtypes:
- Polycythemia vera is the single most frequent MPN in Budd-Chiari syndrome and is significantly more prevalent in BCS compared to other forms of splanchnic vein thrombosis 1, 3
- Essential thrombocythemia is the second most common MPN subtype 1
- Primary myelofibrosis occurs less frequently but is still recognized as a causative disorder 1
The AASLD guidelines specifically identify polycythemia vera and essential thrombocytosis as the predominant myeloproliferative disorders causing Budd-Chiari syndrome 1.
Diagnostic Considerations
JAK2V617F Mutation Screening
The JAK2V617F mutation is detected in approximately 41-42% of Budd-Chiari syndrome patients, making it a critical diagnostic marker 2, 4, 3. This mutation testing is particularly valuable because:
- It identifies MPN in 17.1% of BCS patients who lack typical hematologic features of myeloproliferative disease 3
- The mutation is found in approximately 45% of Budd-Chiari patients overall 2
- JAK2V617F screening should be an initial test for MPN in all patients presenting with Budd-Chiari syndrome 4, 3
Hematologic Parameters
Even when overt MPN is not apparent, specific blood count thresholds warrant JAK2V617F testing 4:
- Platelet count ≥190,000/mm³ (sensitivity/specificity threshold for JAK2V617F positivity) 4
- White blood cell count ≥8,150/mm³ (sensitivity/specificity threshold for JAK2V617F positivity) 4
- Thrombocytosis is present in approximately 42.5% of patients with spontaneous erythroid colony formation and Budd-Chiari syndrome 5
Additional Diagnostic Testing
Beyond JAK2V617F mutation analysis, comprehensive MPN workup should include 2:
- Calreticulin (CALR) mutation screening 1, 2
- MPL mutation testing 1
- Bone marrow biopsy and histology to identify latent or unclassified myeloproliferative disorders 2, 5
- Spontaneous erythroid colony (EEC) formation testing, which identifies PMD in 78% of apparently idiopathic Budd-Chiari cases 5
Clinical Pitfalls and Important Caveats
Latent Myeloproliferative Disease
A critical pitfall is missing latent or unclassified myeloproliferative disorders that do not meet classical diagnostic criteria 5. Using spontaneous EEC formation and bone marrow biopsies, primary myeloproliferative disorders are identified in 78% of apparently idiopathic Budd-Chiari cases, far exceeding the 10% diagnosed using classical PV criteria alone 5.
Patient Demographics
Budd-Chiari syndrome associated with MPN predominantly affects females younger than 45 years, which differs from the typical MPN demographic 5. This should lower the threshold for MPN screening in young women presenting with hepatic vein thrombosis.
Normal Blood Counts Do Not Exclude MPN
Approximately 30% of splanchnic vein thrombosis patients without overt MPN (including those with normal blood counts or cytopenias) still harbor JAK2V617F mutations 4. Therefore, molecular testing must be performed regardless of hematologic parameters.
Management Implications
Once MPN is identified as the underlying cause of Budd-Chiari syndrome 2:
- Immediate and indefinite anticoagulation is required to prevent clot extension 2
- Cytoreductive therapy with hydroxyurea or interferon-alpha to normalize blood counts 6, 2
- Maintain hematocrit <45% in polycythemia vera patients 6, 2
- Aspirin 81-100 mg daily for vascular symptoms 6
The best transplantation outcomes occur in patients with thrombosis limited to hepatic veins where the underlying MPN can be corrected by liver replacement 1.