What test should be ordered to evaluate for an underlying myeloproliferative neoplasm in a patient with Budd-Chiari syndrome and thrombocytosis?

Testing for JAK2 Mutation in Budd-Chiari Syndrome with Thrombocytosis

Testing for JAK2 mutation is the most appropriate next step for this patient with Budd-Chiari syndrome and thrombocytosis, as myeloproliferative neoplasms are the most common underlying cause of this condition. 1

Rationale for JAK2 Mutation Testing

The patient presents with several key findings that strongly suggest an underlying myeloproliferative neoplasm (MPN):

1. Budd-Chiari syndrome - Hepatic venous outflow obstruction confirmed by Doppler ultrasonography and CT
2. Persistent thrombocytosis - Platelet count >600,000/μL on multiple occasions
3. Hepatomegaly - Enlarged liver with right upper quadrant tenderness
4. New-onset ascites - A common presentation of Budd-Chiari syndrome

Epidemiology and Association

• MPNs are found in approximately 49% of patients with Budd-Chiari syndrome 1
• JAK2V617F mutation is detected in 29% of Budd-Chiari syndrome patients 1
• Even with normal peripheral blood counts, JAK2 mutations can be present in splanchnic vein thrombosis 1

Diagnostic Algorithm for Budd-Chiari Syndrome

1. Confirm diagnosis (already completed via Doppler ultrasonography and CT)
2. Investigate for underlying prothrombotic factors (current step)
   • Testing for myeloproliferative neoplasms is a high priority (Grade A1 recommendation) 1
   • JAK2V617F mutation testing should be performed even in patients with normal blood counts 1
3. If JAK2V617F negative, proceed with:
   • Calreticulin mutation screening
   • Bone marrow histology if both are negative 1
   • Referral to hematology

Why JAK2 Testing Over Other Options

Why not flow cytometry?

Flow cytometry would be appropriate for testing for paroxysmal nocturnal hemoglobinuria (PNH), which is found in approximately 19% of Budd-Chiari syndrome cases 1. However, the patient has thrombocytosis without anemia or hemolysis, making MPN a more likely diagnosis than PNH.

Why not peripheral blood smear?

While a peripheral blood smear might show features suggestive of MPN, it is not as specific as molecular testing. The patient already has documented thrombocytosis, and JAK2 mutation testing provides more definitive evidence of an underlying MPN.

Clinical Implications of JAK2 Mutation Detection

If JAK2V617F mutation is detected:

1. Treatment implications:

   • Anticoagulation should be continued indefinitely 1
   • Cytoreductive therapy (hydroxyurea or interferon) should be considered to normalize blood counts 1

2. Prognostic implications:

   • Up to 90.9% of patients who develop overt MPN after Budd-Chiari syndrome diagnosis are JAK2V617F positive 2
   • JAK2V617F mutation can be detected even before the development of overt MPN 2

Important Caveats

• False negatives: Some patients with MPN may have mutations in genes other than JAK2 (e.g., MPL or CALR) 3
• Timing of thrombocytosis: Some patients may present with normal platelet counts initially and develop thrombocytosis later 3
• Need for comprehensive evaluation: Additional thrombophilia testing should still be performed as multiple risk factors may coexist 1

JAK2 mutation testing represents the most direct path to identifying the underlying cause of this patient's Budd-Chiari syndrome, which will guide appropriate long-term management and potentially prevent future thrombotic events.