What are the diagnostic criteria for Budd-Chiari syndrome in a patient with polycythemia vera (a type of myeloproliferative neoplasm)?

Diagnostic Criteria for Budd-Chiari Syndrome

Budd-Chiari syndrome is diagnosed by demonstrating hepatic venous outflow obstruction at any level from the small hepatic veins to the junction of the inferior vena cava with the right atrium, using imaging studies combined with identification of underlying thrombotic disorders, particularly myeloproliferative neoplasms like polycythemia vera. 1

Clinical Presentation Warranting Diagnostic Evaluation

The diagnosis should be suspected when patients present with:

• Hepatomegaly and ascites (often severe) 2
• Abdominal pain in the right upper quadrant 1
• Features of portal hypertension 1
• In the context of polycythemia vera: BCS may be the first manifestation of the underlying myeloproliferative disorder, particularly in young women 3

Imaging Confirmation of Venous Obstruction

Hepatic venography is the definitive test to confirm the site of hepatic vein obstruction or suggest its presence 4. Modern imaging modalities play a critical role:

• Doppler ultrasound, CT, or MRI can demonstrate obstruction of hepatic venous outflow 1
• Hepatic scintiscanning shows characteristic predominant central localization of radiocolloid, reflecting disproportionate enlargement of the caudate lobe (which has separate venous drainage that may be preserved when main hepatic veins are occluded) 4
• Inferior vena cavography demonstrates characteristic narrowing and distortion of the vein throughout its intrahepatic course, or complete occlusion in some cases 4

Histological Confirmation

Percutaneous liver biopsy confirms the diagnosis in the majority of patients, showing features consistent with hepatic venous outflow obstruction 4. This should be performed when imaging is suggestive but not definitive.

Mandatory Evaluation for Underlying Thrombotic Disorders

Critical pitfall: Failure to identify the underlying cause, particularly myeloproliferative neoplasms, leads to inadequate long-term management 3.

Screen for Polycythemia Vera Using WHO Criteria

When BCS is diagnosed, immediately evaluate for polycythemia vera using the 2008 WHO criteria, which require both major criteria plus one minor criterion, OR the first major criterion plus two minor criteria 5:

Major Criteria:

1. Hemoglobin ≥18.5 g/dL in men, ≥16.5 g/dL in women (or other evidence of increased red cell volume) 5
2. Presence of JAK2 V617F or JAK2 exon 12 mutation 5

Minor Criteria:

1. Bone marrow biopsy showing hypercellularity with trilineage growth (panmyelosis) 5
2. Serum erythropoietin level below the reference range 5
3. Endogenous erythroid colony formation in vitro 5

Additional Thrombophilia Screening

Routine screening for inherited thrombophilic states is essential in young women with BCS and polycythemia vera 3:

• Factor V Leiden mutation (prevalence three times greater in BCS patients) 6
• Protein C deficiency 2
• Paroxysmal nocturnal hemoglobinuria 1
• Other hypercoagulable states 1

Diagnostic Algorithm

1. Suspect BCS when hepatomegaly, ascites, or portal hypertension develops, especially with unusual thrombosis patterns 5
2. Confirm venous obstruction with hepatic venography or cross-sectional imaging (Doppler ultrasound, CT, MRI) 1, 4
3. Perform liver biopsy if imaging is equivocal 4
4. Immediately screen for polycythemia vera using complete blood count, JAK2 mutation testing, serum erythropoietin level, and bone marrow biopsy if indicated 5, 3
5. Test for inherited thrombophilias, particularly in young patients without obvious secondary causes 3, 6

Critical Clinical Pearls

• Multiple etiological factors can coexist in the same patient (e.g., polycythemia vera plus Factor V Leiden mutation) 6
• Myeloproliferative disorders are the most common cause of BCS, with polycythemia rubra vera being the most frequent specific etiology 4, 1
• BCS can present as fulminant acute liver failure on rare occasions, requiring urgent recognition 6
• The clinical course is typically chronic, but aggressive multidisciplinary management including cytostatic drugs and anticoagulation is required when associated with myeloproliferative disorders 3