Management of Slightly Elevated Platelets and Hematocrit
The priority is to determine whether this represents a primary myeloproliferative neoplasm (MPN) such as polycythemia vera or essential thrombocythemia, which requires risk stratification and potential cytoreductive therapy, versus secondary causes that need different management. 1, 2
Initial Diagnostic Approach
Obtain JAK2 mutation testing immediately - this is the cornerstone of diagnosis for myeloproliferative neoplasms. 3, 4, 5, 6, 7
- JAK2 mutation is present in nearly 100% of polycythemia vera cases and approximately 50-70% of essential thrombocythemia cases 3, 4, 5
- If JAK2 is negative in suspected polycythemia vera, measure serum erythropoietin level - normal or elevated EPO combined with absent JAK2 mutation excludes PV 3, 4, 5
- For thrombocytosis with negative JAK2, test for CALR and MPL mutations (present in approximately 25% and 3% of ET cases respectively) 5, 6, 7
- Bone marrow biopsy with morphology is essential to distinguish essential thrombocythemia from prefibrotic myelofibrosis, which has different prognosis and management 5, 6, 7
Risk Stratification for Primary Myeloproliferative Neoplasms
For Polycythemia Vera:
Two risk categories determine treatment intensity: 6, 7
- High-risk: Age >60 years OR history of thrombosis
- Low-risk: Age ≤60 years AND no thrombosis history
For Essential Thrombocythemia:
Four risk categories guide management: 6, 7
- Very low-risk: Age ≤60 years, no thrombosis history, JAK2 wild-type
- Low-risk: Age ≤60 years, no thrombosis history, JAK2 mutation present
- Intermediate-risk: Age >60 years, no thrombosis history, JAK2 wild-type
- High-risk: Thrombosis history present OR age >60 years with JAK2 mutation
Treatment Recommendations
For Polycythemia Vera:
All patients require phlebotomy to maintain hematocrit <45% - this is non-negotiable regardless of risk category. 6, 7
All patients should receive aspirin 81 mg once or twice daily unless contraindications exist (such as extreme thrombocytosis with acquired von Willebrand syndrome). 6, 7
High-risk patients require cytoreductive therapy with hydroxyurea as first-line treatment, targeting platelet count <400,000/μL. 1, 2, 6, 7
- Hydroxyurea initial dosage: 500 mg twice daily 8
- Second-line options if hydroxyurea fails: interferon-α (3 million units subcutaneously 3 times weekly) or busulfan (4 mg/day) 8, 6, 7
- Ruxolitinib is NOT recommended unless severe protracted pruritus or marked splenomegaly unresponsive to other drugs 6, 7
For Essential Thrombocythemia:
Very low-risk patients may not require any therapy - observation alone is acceptable. 6, 7
Low-risk patients should receive aspirin 81-100 mg daily. 1, 6, 7
Intermediate-risk patients should receive aspirin; cytoreductive therapy is not mandatory but may be considered if symptomatic. 1, 6, 7
High-risk patients require cytoreductive therapy with hydroxyurea plus aspirin, targeting platelet count <400,000/μL. 1, 2, 6, 7
Critical Pitfalls to Avoid
Screen for acquired von Willebrand syndrome before starting aspirin if platelet count >1,000 × 10⁹/L - extreme thrombocytosis paradoxically increases bleeding risk. 3, 4, 5, 6, 7
Do NOT use platelet count alone to guide treatment decisions - risk stratification is based on age and thrombosis history, not platelet number. 1, 2
Erythromelalgia (burning pain in hands/feet with erythema) responds dramatically to aspirin within days - this symptom is particularly common in myeloproliferative disorders and confirms the diagnosis. 8
Monitor for disease transformation: 10-year leukemic transformation risk is <1% for ET and 3% for PV; fibrotic transformation is <1%/10% for ET and 10% for PV. 3, 4, 5
Special Considerations
If thrombosis develops with thrombocytosis and platelet count >50 × 10⁹/L, initiate full therapeutic anticoagulation immediately plus urgent cytoreduction. 1, 2
Cardiovascular risk factors (hypertension, diabetes, smoking, hyperlipidemia) are additional thrombosis risk factors that should influence treatment intensity. 4, 5
For women of childbearing age with high-risk disease, interferon-α is preferred over hydroxyurea due to teratogenicity concerns with hydroxyurea and busulfan. 8
Monitoring
Regular complete blood count monitoring is essential to assess response to cytoreductive therapy and detect disease progression (leukocytosis is a poor prognostic sign). 1, 6, 7
Monitor for hydroxyurea toxicity: neutropenia and mucocutaneous changes (leg ulcers, oral ulcers, skin hyperpigmentation). 8