What is the recommended workup and management for a patient with suspected polycythemia vera (PV), including a patient with a history of thrombotic events or myeloproliferative neoplasms?

Workup for Polycythemia Vera

All patients with suspected polycythemia vera require JAK2V617F mutation testing as the initial diagnostic step, followed by complete blood count, peripheral blood smear, and bone marrow biopsy if JAK2 testing is negative or diagnosis remains uncertain. 1

Initial Diagnostic Testing

Essential Laboratory Studies

• JAK2V617F mutation testing is mandatory as the first-line molecular test, present in >95% of PV patients 1, 2, 3
• Complete blood count (CBC) to document erythrocytosis (hemoglobin >16.5 g/dL in men or >16.0 g/dL in women), and assess for thrombocytosis (present in 53%) and leukocytosis (present in 49%) 3
• Peripheral blood smear to evaluate cell morphology and rule out other causes 1

Secondary Molecular Testing (If JAK2V617F Negative)

• Calreticulin (CALR) mutation screening should be performed in JAK2V617F-negative patients 1
• Bone marrow aspirate and biopsy with histology is indicated when both JAK2V617F and CALR mutations are negative, or when diagnosis remains uncertain 1
• Refer to hematologist for further evaluation in mutation-negative cases 1

Thrombophilia and Prothrombotic Risk Assessment

Comprehensive Thrombophilia Screening

In patients with thrombotic events or unusual site thrombosis (splanchnic veins), perform complete thrombophilia workup 1:

• Protein C, protein S, and antithrombin levels 1
• Factor V Leiden (FVL) mutation 1
• Prothrombin G20210A gene variant 1
• Anti-phospholipid antibodies (APA) - if positive, repeat after 12 weeks 1
• Paroxysmal nocturnal hemoglobinuria (PNH) testing in patients with splanchnic vein thrombosis 1

Additional Prothrombotic Evaluation

• Screen for autoimmune disorders as part of comprehensive prothrombotic workup 1
• Evaluate for local risk factors including intra-abdominal inflammatory conditions and abdominal malignancies, particularly in patients with Budd-Chiari syndrome or portal vein thrombosis 1

Baseline Disease Assessment

Clinical Evaluation

• Document thrombosis history (arterial events occur in 16%, venous events in 7% at or before diagnosis) 3
• Assess for disease-related symptoms: pruritus (33%), erythromelalgia (5.3%), transient visual changes (14%) 3
• Physical examination for splenomegaly (present in 36% of patients) 3

Coagulation Studies

• Coagulation tests to evaluate for acquired von Willebrand disease are recommended for patients with elevated platelet count (≥1000 × 10⁹/L), splenomegaly, or unexplained bleeding 1, 3
• This is critical before high-risk surgical procedures 1

Risk Stratification

Classify patients into risk categories to guide treatment decisions 1:

High-Risk Criteria

• Age ≥60 years and/or
• History of thrombosis 1

Low-Risk Criteria

• Age <60 years AND
• No history of thrombosis 1

Additional Baseline Studies

Cardiovascular Risk Assessment

• Evaluate all cardiovascular risk factors including hypertension, hyperlipidemia, diabetes, and smoking status 1, 4
• Mandatory smoking cessation counseling 4

Imaging Studies

• Abdominal ultrasound or CT if splenomegaly suspected or to evaluate for splanchnic vein thrombosis 1

Critical Pitfalls to Avoid

• Do not rely solely on hematocrit levels - in PV, plasma volume expansion can mask true erythrocytosis, particularly in young women with isolated thrombocytosis 5
• Do not stop workup after finding one risk factor - identification of one prothrombotic factor should not deter from looking for additional risk factors 1
• Do not delay JAK2V617F testing - this is the cornerstone diagnostic test and should be ordered immediately when PV is suspected 1, 2
• Do not overlook unusual thrombosis sites - PV can present with splanchnic vein thrombosis (Budd-Chiari syndrome, portal vein thrombosis) requiring specific evaluation 1, 3