What is the treatment for a 36-year-old female with leukocytosis and thrombocytosis?

Treatment Approach for Leukocytosis and Thrombocytosis in a 36-Year-Old Female

The first priority is to establish whether this represents a primary myeloproliferative neoplasm (particularly chronic myeloid leukemia or essential thrombocythemia) versus a reactive process, as this fundamentally determines treatment strategy. 1

Immediate Diagnostic Workup Required

Before initiating any treatment, the following tests are mandatory:

• Peripheral blood fluorescence in situ hybridization (FISH) using dual probes for BCR and ABL genes to confirm or exclude chronic myeloid leukemia (CML), as this is the most critical diagnosis to rule out given the combined leukocytosis and thrombocytosis 1
• JAK2V617F, CALR, and MPL mutation testing to evaluate for essential thrombocythemia (ET) or polycythemia vera, as approximately 90% of ET patients express one of these mutations 2
• Bone marrow biopsy with cytogenetics remains the cornerstone of diagnosis and is essential to distinguish between myeloproliferative neoplasms and exclude prefibrotic myelofibrosis 2
• Peripheral blood smear examination to verify automated counts and exclude spurious results from platelet clumping, which can falsely elevate WBC counts 3

The microcytic indices (MCH 25.9, MCHC 31.1) and elevated RDW (16.1) suggest possible iron deficiency, which is relevant as this can mask polycythemia vera 2.

Treatment Algorithm Based on Diagnosis

If CML is Confirmed (BCR-ABL1 Positive):

Tyrosine kinase inhibitors should be started immediately once the Philadelphia chromosome or BCR-ABL1 fusion gene is detected 1

• Imatinib is the first-line treatment for chronic phase CML 1, 4
• Hydration is usually sufficient for tumor lysis syndrome prevention; allopurinol is only required if tumor lysis parameters are deranged or uric acid levels increase after therapy initiation 1
• BCR-ABL transcript levels must be measured every 3 months during treatment 1
• Bone marrow cytogenetics should be performed at 6 and 12 months from therapy initiation 1

Important caveat: Young females with CML can present with marked thrombocytosis (>2,000×10³/µL) without significant leukocytosis, potentially mimicking essential thrombocythemia 5. This subgroup may have normal neutrophil alkaline phosphatase scores and lack immature myeloid cells in peripheral blood, making diagnosis challenging 5.

If Essential Thrombocythemia is Confirmed:

Risk stratification determines treatment intensity 2:

• Very low-risk (age ≤60 years, no thrombosis history, JAK2 wild-type): May not require therapy 2
• Low-risk (age ≤60 years, no thrombosis history, JAK2 mutation present): Aspirin 81 mg once or twice daily 2
• Intermediate-risk (age >60 years, no thrombosis history, JAK2 wild-type): Aspirin therapy advised; cytoreductive therapy not mandatory 2
• High-risk (thrombosis history or age >60 with JAK2 mutation): Cytoreductive therapy recommended 2

For this 36-year-old patient, if JAK2 wild-type, observation alone may be appropriate; if JAK2-mutated, aspirin therapy is indicated 2

Cytoreductive Therapy When Indicated:

Hydroxyurea is the first-line drug of choice for cytoreductive therapy in both ET and CML when needed 1, 4, 2

• Dosing for symptomatic thrombocytosis: Hydroxyurea 2-4 g per day to restore platelet counts to <400×10⁹/L 1, 4
• Dosing for symptomatic leukocytosis: Hydroxyurea 50-60 mg/kg per day until WBC <10-20×10⁹/L 1
• Time to 50% WBC reduction: 1-2 weeks 1

Second-line options include interferon-α and busulfan 2. Interferon is particularly important for women of childbearing age, as it is the preferred agent during pregnancy 1, 4.

Anagrelide can be considered as second-line therapy specifically for essential thrombocythemia 1, 4

Management of Symptomatic Disease:

For symptomatic thrombocytosis (platelet count 426×10³/µL is mildly elevated but may be symptomatic):

• Evaluate for microvascular symptoms (headache, visual disturbances, erythromelalgia) 1
• Consider age, cardiovascular risk factors, and degree of thrombocytosis when deciding treatment 1
• Aspirin is contraindicated in this age group if diagnosis is CML due to risk of acquired von Willebrand syndrome with high platelet counts and bleeding complications 1
• Low-dose aspirin cannot be recommended in pediatric/young patients with CML due to risk of Reye syndrome and platelet dysfunction 1

For symptomatic leukocytosis (WBC 12.0×10³/µL is only mildly elevated):

• Treatment options include hydroxyurea, apheresis, or tyrosine kinase inhibitors if CML 1, 4
• Apheresis should be reserved for severe symptoms of leukostasis 1, 4

Critical Pitfalls to Avoid

1. Do not assume reactive thrombocytosis without molecular testing, especially in a young female where CML can present atypically with predominant thrombocytosis 5

2. Verify automated counts with peripheral smear, as platelet clumping can cause spurious leukocytosis and falsely low platelet counts 3

3. Do not use aspirin empirically before establishing diagnosis, as bleeding risk may be elevated despite normal or high platelet counts due to acquired von Willebrand syndrome in myeloproliferative disorders 1

4. Evaluate for iron deficiency given the microcytic indices, as this can mask underlying polycythemia vera 2

5. If starting hydroxyurea, monitor for Grade 3-4 cytopenias: Hold drug if ANC <1000/mm³ until ANC ≥1500/mm³, then resume at reduced dose 1

Monitoring Strategy

Once diagnosis is established and treatment initiated:

• Complete blood counts weekly until stable, then every 2-4 weeks 1
• BCR-ABL transcript levels every 3 months if CML 1, 4
• Bone marrow cytogenetics at 6 and 12 months if CML 1
• Assess for thrombotic and bleeding complications at each visit 1, 2