Management of Leukocytosis and Thrombocytosis
The management of a patient with leukocytosis and thrombocytosis should focus on identifying and treating the underlying cause, with cytoreductive therapy (such as hydroxyurea) recommended for symptomatic cases or those with high risk of complications. 1
Initial Assessment
Laboratory Evaluation
- Complete blood count with differential
- Peripheral blood smear examination
- Bone marrow aspiration and biopsy if myeloproliferative neoplasm is suspected
- Molecular testing for:
- BCR-ABL1 fusion gene (Philadelphia chromosome)
- JAK2, CALR, and MPL mutations
- Comprehensive metabolic panel
- Inflammatory markers (CRP, ESR)
Clinical Evaluation
- Assess for signs of infection (fever, tachycardia, localized symptoms)
- Evaluate for symptoms of leukostasis (neurological symptoms, visual disturbances)
- Check for bleeding or thrombotic complications
- Assess spleen size (splenomegaly is common in myeloproliferative disorders)
Differential Diagnosis
Primary Causes (Clonal)
- Myeloproliferative neoplasms:
- Essential thrombocythemia
- Chronic myeloid leukemia
- Polycythemia vera
- Primary myelofibrosis
Secondary Causes (Reactive)
- Infections (most common cause of secondary thrombocytosis) 2
- Inflammation/autoimmune disorders
- Iron deficiency anemia
- Post-splenectomy
- Malignancy
- Tissue damage/trauma
- Drug-induced
Management Approach
For Symptomatic Leukocytosis
Cytoreductive therapy options: 1, 3
- Hydroxyurea (first-line): 15-30 mg/kg/day, adjust to maintain WBC <10,000/μL
- Leukapheresis: For severe symptoms of leukostasis or WBC >100,000/μL
- TKIs: If BCR-ABL1 positive (CML)
Supportive measures:
- Aggressive hydration
- Monitor for tumor lysis syndrome
- Allopurinol if at risk for hyperuricemia
For Thrombocytosis
Cytoreductive therapy options: 1
- Hydroxyurea: First-line for symptomatic thrombocytosis
- Anti-aggregants: Consider low-dose aspirin for thrombosis prevention
- Anagrelide: Alternative for hydroxyurea intolerance
- Apheresis: For severe symptomatic thrombocytosis
Risk stratification for thrombotic complications: 4
- 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 mutation present
- High risk: Thrombosis history or age >60 years with JAK2 mutation
Treatment Algorithm
Asymptomatic with mild elevations:
- Monitor CBC regularly
- Investigate underlying cause
- No immediate cytoreductive therapy needed
Symptomatic or high-risk features:
- Start hydroxyurea at 15-30 mg/kg/day
- Target platelet count <450,000/μL and WBC <10,000/μL
- Monitor CBC every 2-4 weeks until stable
Emergency situations:
- For leukostasis: Consider leukapheresis or exchange transfusion
- For severe thrombocytosis with bleeding: Consider platelet apheresis
Special Considerations
- CML with thrombocytosis: May present with marked thrombocytosis without significant leukocytosis, especially in young females 5
- Infection-related thrombocytosis: More common in patients with diabetes, dementia, indwelling prostheses, or quadriplegia/paraplegia 2
- Laboratory artifacts: Verify abnormal counts with peripheral smear review to exclude spurious results 6
Monitoring
- CBC with differential every 2-4 weeks until counts stabilize
- Once stable, CBC every 1-3 months
- Bone marrow evaluation at 6 and 12 months if myeloproliferative neoplasm is diagnosed 1
- Monitor for complications of cytoreductive therapy
Pitfalls to Avoid
- Treating the numbers without identifying the underlying cause
- Missing CML diagnosis in patients with isolated thrombocytosis
- Overlooking infection as a common cause of secondary thrombocytosis
- Failing to recognize laboratory artifacts causing spurious results
- Delaying treatment in patients with symptoms of leukostasis or thrombosis
Remember that infection is a common cause of secondary thrombocytosis and should be thoroughly investigated, especially in patients with fever, tachycardia, or other signs of infection 2, 7.