In a young male with hepatic hemangiomas who presents with Budd‑Chiari syndrome, what are the likely etiologies and how should the work‑up and management be approached?

Budd-Chiari Syndrome in a Young Male with Hepatic Hemangiomas: Etiologies and Management

Most Likely Etiologies

In a young male presenting with Budd-Chiari syndrome, myeloproliferative neoplasms are the single most important cause, accounting for approximately 49% of cases, and must be investigated first even when hepatic hemangiomas are present. 1, 2

Primary Prothrombotic Causes (Present in 84% of Cases)

Myeloproliferative Neoplasms (49% of cases):

• Polycythemia vera and essential thrombocythemia are the most common subtypes 2, 3
• JAK2 V617F mutation is detected in approximately 29-30% of all Budd-Chiari patients and serves as the molecular marker 1, 2
• Critical point: Even with normal peripheral blood counts, JAK2 V617F testing is mandatory 4
• If JAK2 V617F is negative, calreticulin mutation screening must follow 4, 1
• If both mutations are negative, bone marrow histology should be performed with hematology referral 4

Inherited Thrombophilias:

• Factor V Leiden mutation (7-32% prevalence, confers 4-11 fold increased risk) 2
• Prothrombin G20210A gene variant (2-fold increased risk) 2
• Protein C, protein S, and antithrombin deficiencies (0-5% prevalence) 2

Acquired Thrombophilias:

• Antiphospholipid antibodies (5-15% prevalence; requires repeat testing after 12 weeks for confirmation) 2, 5
• Paroxysmal nocturnal hemoglobinuria (requires flow cytometry testing) 2

Multifactorial Nature (Critical Concept)

46% of patients have two or more concurrent prothrombotic risk factors, and 18% have three or more risk factors. 2 This means:

• Identifying one risk factor should never stop the investigation 4
• Over 60% of patients with inherited thrombophilia have at least one additional risk factor 2
• The hepatic hemangiomas in this patient may be incidental findings rather than causative

Local Risk Factors to Exclude

• Solid malignancies or cysts compressing the hepatic venous tract 2
• Membranous webs of the inferior vena cava 2, 6, 7
• Intra-abdominal inflammatory conditions (e.g., Behçet disease) 2
• Note: Hepatic hemangiomas themselves are benign vascular lesions and are not typically causative of Budd-Chiari syndrome, but must be distinguished from malignancy

Mandatory Diagnostic Work-Up

Immediate Imaging

Doppler ultrasound is the first-line test (sensitivity >75%) and should be performed immediately. 4, 1

• If Doppler is negative but clinical suspicion remains high, contrast-enhanced MRI or CT must be performed immediately 1
• Venography is reserved for uncertain diagnoses or pre-procedural anatomic characterization 4

Complete Thrombophilia Screening (Do Not Delay Anticoagulation While Awaiting Results)

All patients require the following panel: 4, 2

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

Myeloproliferative Neoplasm Testing (Mandatory Even with Normal Blood Counts)

Sequential testing algorithm: 4, 1

1. JAK2 V617F mutation testing first
2. If negative, calreticulin mutation screening
3. If both negative, bone marrow histology with hematology referral

Additional Testing

• Flow cytometry for paroxysmal nocturnal hemoglobinuria 2
• Autoimmune disorder screening 4
• Imaging to exclude intra-abdominal malignancies and inflammatory conditions 4

Concurrent Portal Vein Thrombosis

Approximately 15% of Budd-Chiari patients have simultaneous portal vein thrombosis at presentation, which significantly worsens prognosis. 4, 2 This must be assessed on initial imaging.

Immediate Management

Anticoagulation (Start Immediately)

Anticoagulation must be started as soon as Budd-Chiari syndrome is diagnosed and continued indefinitely. 1, 8

• Initial therapy: low-molecular-weight heparin for at least 5-7 days 1
• Overlap with warfarin targeting INR 2.0-3.0 1
• Do not delay anticoagulation while awaiting complete thrombophilia work-up 1
• Portal hypertension complications (varices, ascites) are NOT contraindications to anticoagulation when adequately managed 1
• Bleeding complications have decreased from ≈50% to ≈17% with modern protocols 1

Treatment of Underlying Myeloproliferative Neoplasm (If Identified)

Targeted therapy is mandatory: 4, 1

• Hydroxyurea or interferon-α to normalize peripheral blood counts 4, 1
• In polycythemia vera, maintain hematocrit <45% 4, 1
• Anticoagulation must be continued indefinitely in myeloproliferative neoplasm patients 4

Portal Hypertension Management

Esophageal varices are present in approximately 58% of Budd-Chiari patients. 4, 1

• Primary prophylaxis with non-selective beta-blockers or endoscopic variceal ligation for high-risk varices 1
• Follow the same treatment recommendations as for cirrhotic portal hypertension 4

Stepwise Interventional Algorithm

Step 1: Medical Management (All Patients)

• Anticoagulation plus treatment of underlying prothrombotic disorder 1
• Management of ascites and varices per cirrhosis guidelines 4
• Clinical response and Doppler ultrasound surveillance guide progression 1

Step 2: Angioplasty/Stenting

Indicated for short, focal venous stenoses or membranous webs. 1, 6, 7

• Present in ≈60% of patients with IVC obstruction and ≈25-30% with hepatic vein obstruction 1
• Stent placement reduces restenosis rates compared with angioplasty alone 1
• Pitfall: Misplaced stents can jeopardize subsequent TIPS or liver transplantation 1

Step 3: Transjugular Intrahepatic Portosystemic Shunt (TIPS)

TIPS is pursued when: 1

• Medical therapy fails
• Angioplasty/stenting is ineffective or not feasible
• Fulminant Budd-Chiari syndrome occurs
• Recurrent variceal bleeding persists despite optimal medical/endoscopic therapy

Outcomes: 1

• Symptom relief >70%
• 5-year survival >70%
• OLT-free survival 88% at 1 year and 78% at 5 years
• Hepatic encephalopathy in ≈15% of patients

Technical considerations: 1

• Use PTFE-covered stents for superior primary patency
• Transcaval approach required in >45% of cases with complete hepatic vein thrombosis
• Doppler ultrasound surveillance every 6 months post-procedure

Step 4: Liver Transplantation

Reserved for patients who fail all other therapies or present with fulminant hepatic failure. 1

• TIPS often used as a bridge to transplantation 1
• Post-transplant anticoagulation should be initiated early and continued lifelong unless the underlying prothrombotic disorder has been definitively corrected 1

Prognostic Considerations

• BCS-TIPS score >7 reliably predicts poor outcomes and should prompt transplant evaluation 1
• Concurrent portal vein thrombosis (15% of cases) worsens prognosis 4, 2
• Screening for hepatocellular carcinoma with hepatospecific-contrast MRI is recommended due to atypical hypervascular nodule development 1

Critical Pitfalls to Avoid

• Do not assume hepatic hemangiomas are causative; they are likely incidental findings (general medicine knowledge)
• Do not stop investigating after finding one risk factor; 46% have multiple concurrent factors 2
• Do not omit myeloproliferative neoplasm testing even when another clear cause is identified 1
• Do not delay anticoagulation while awaiting thrombophilia results 1
• Do not withhold anticoagulation solely because of varices or ascites 1