Workup for Essential Thrombocythemia and Initiate Risk-Stratified Treatment
This 26-year-old patient with chronic thrombocytosis, neurological symptoms (headaches, peripheral neuropathy), and hepatomegaly requires immediate evaluation for essential thrombocythemia (ET), a myeloproliferative neoplasm, followed by risk-stratified cytoreductive therapy if confirmed.
Diagnostic Workup
Obtain JAK2 V617F mutation testing, CALR mutation, and MPL mutation testing to confirm the diagnosis of essential thrombocythemia, as 86% of primary thrombocytosis cases have at least one molecular marker indicative of myeloproliferative neoplasms 1. These driver mutations have simplified the diagnostic approach and are essential for distinguishing primary from secondary thrombocytosis 1.
Perform bone marrow examination with aspirate and biopsy to exclude other myeloproliferative disorders such as polycythemia vera or primary myelofibrosis 2. Flow cytometry and cytogenetic testing should be included to rule out chronic lymphocytic leukemia or other lymphoproliferative disorders that can present with thrombocytosis 2.
Rule out secondary causes of thrombocytosis by checking for infection (complete infectious workup), tissue injury, chronic inflammatory conditions, and iron deficiency anemia, which collectively account for over 70% of secondary thrombocytosis cases 1. However, the 7-year chronicity, neurological symptoms, and hepatomegaly strongly suggest primary thrombocythemia rather than reactive thrombocytosis.
Risk Stratification
Classify this patient as intermediate-risk based on age ≤60 years with presence of JAK2 mutation (if positive) and symptomatic disease 3. The neurological manifestations (headaches and peripheral neuropathy) are classic complications of essential thrombocythemia, occurring in up to 64% of patients, and indicate active disease requiring treatment 4, 5.
The combination of headaches, peripheral neuropathy, and hepatomegaly represents significant disease burden. Headaches in ET are associated with considerable morbidity and indicate microvascular complications 5. Peripheral neuropathy, though rare, suggests either intraneural hemorrhage or autoimmune mechanisms affecting both platelets and myelin 6.
Treatment Recommendations
Initiate hydroxyurea as first-line cytoreductive therapy targeting platelet count <400,000/μL 3. Hydroxyurea is the standard cytoreductive agent recommended by the National Comprehensive Cancer Network for symptomatic patients with essential thrombocythemia 3.
Alternative: Consider interferon alfa-2b or peginterferon alfa-2a/2b given the patient's young age (26 years), as interferon may be preferable in younger patients who may require decades of treatment 3. Interferon avoids the theoretical long-term leukemogenic risk of hydroxyurea in young patients.
Add low-dose aspirin 81-100 mg daily for vasomotor symptoms (headaches, peripheral neuropathy) once platelet count is confirmed to be <1,500 × 10⁹/L 3. Aspirin addresses the microvascular complications causing neurological symptoms 4. However, if platelet count exceeds 1,500 × 10⁹/L, aspirin must be avoided due to paradoxical hemorrhagic risk from acquired von Willebrand disease 3.
Monitoring and Follow-up
Monitor platelet count weekly initially during cytoreductive therapy titration, then monthly once stable 3. The neurological symptoms (headaches, peripheral neuropathy) should improve with platelet reduction, as these manifestations respond satisfactorily to treatment in the vast majority of cases 4.
Assess for thrombotic complications given that primary thrombocytosis carries significantly higher thrombosis risk compared to secondary thrombocytosis 1. The median platelet count and thrombosis incidence are both elevated in primary versus secondary thrombocytosis 1.
Critical Pitfalls to Avoid
Do not delay treatment based on platelet count alone in this symptomatic patient. Treatment decisions for primary thrombocytosis should be based on individual risk factors for thrombosis and symptoms rather than platelet count thresholds 7.
Do not use platelet transfusion even if bleeding develops, as transfusion is not indicated for thrombocytosis 7.
Do not assume secondary thrombocytosis despite the patient's young age. While secondary thrombocytosis accounts for 83% of cases overall 1, the chronicity (7 years), neurological symptoms, and hepatomegaly strongly indicate primary disease requiring molecular testing and bone marrow evaluation.