Thrombocytosis Workup and Management
The workup for thrombocytosis should focus on distinguishing between primary (clonal) and secondary (reactive) causes, with management tailored to the underlying etiology and thrombotic risk.
Initial Diagnostic Approach
Complete Blood Count and Peripheral Smear
- Confirm thrombocytosis (platelet count >450 × 10^9/L)
- Evaluate other cell lines for abnormalities
- Examine peripheral smear for platelet morphology and other cellular abnormalities
Distinguish Primary vs. Secondary Causes
Primary thrombocytosis (12.5% of cases) 1:
- Essential thrombocythemia (ET)
- Polycythemia vera (PV)
- Primary myelofibrosis
- Other myeloproliferative neoplasms (MPNs)
Secondary thrombocytosis (83.1% of cases) 1:
- Tissue injury (32.2%)
- Infection (17.1%)
- Chronic inflammatory disorders (11.7%)
- Iron deficiency anemia (11.1%)
- Post-surgical state
- Malignancy
- Medication-induced
Laboratory Investigations
For suspected primary thrombocytosis:
- JAK2 V617F mutation testing
- CALR and MPL mutation testing if JAK2 negative
- Bone marrow aspiration and biopsy
- Cytogenetic studies
For suspected secondary thrombocytosis:
- Complete iron studies (ferritin, iron, TIBC)
- Inflammatory markers (ESR, CRP)
- Appropriate cultures if infection suspected
- Age-appropriate cancer screening if malignancy suspected
Management Based on Etiology
Primary Thrombocytosis (Myeloproliferative Neoplasms)
Essential Thrombocythemia
- For high-risk patients (age >60 years, prior thrombosis, platelet count >1,500 × 10^9/L): Cytoreductive therapy with anagrelide starting at 0.5 mg four times daily or 1 mg twice daily 2
- For all patients: Low-dose aspirin (unless contraindicated by bleeding risk or extreme thrombocytosis with acquired von Willebrand syndrome)
- For pregnant patients with ET: Consider pegylated interferon-alpha at 45 mcg subcutaneously weekly throughout pregnancy 3
Polycythemia Vera
- Phlebotomy to maintain hematocrit <45%
- Low-dose aspirin
- Consider cytoreductive therapy in high-risk patients
Secondary Thrombocytosis
- Treat the underlying cause - no specific treatment for the thrombocytosis itself is typically required 3
- Secondary thrombocytosis is common but benign; antiplatelet therapy is not necessary 3
- In children with platelet counts >500 × 10^9/L due to secondary causes, no specific treatment is needed 4
Special Considerations
Thrombocytosis with Concurrent Thrombosis
- For cancer-associated thrombosis with platelet count >50 × 10^9/L: Full therapeutic anticoagulation 5
- For platelet counts between 25-50 × 10^9/L: Reduce anticoagulant to 50% of therapeutic dose 5
- For platelet counts <25 × 10^9/L: Hold anticoagulation 5
Extreme Thrombocytosis (>1,000 × 10^9/L)
- Evaluate for acquired von Willebrand syndrome
- If bleeding risk present, avoid aspirin
- Consider cytoreductive therapy in primary thrombocytosis
Pregnancy
- For pregnant women with MPN-related thrombocytosis:
Monitoring and Follow-up
- Regular monitoring of platelet counts
- For primary thrombocytosis: Lifelong follow-up with a hematologist
- For secondary thrombocytosis: Follow-up until resolution of underlying cause and normalization of platelet count
- Monitor for symptoms of thrombosis or bleeding
Pitfalls and Caveats
- Do not assume all thrombocytosis requires treatment; secondary causes rarely need specific therapy for the elevated platelet count
- Avoid antiplatelet agents in patients with bleeding risk or extreme thrombocytosis with acquired von Willebrand syndrome
- Remember that primary thrombocytosis carries a higher risk of thrombosis than secondary thrombocytosis 1
- In children, primary thrombocytosis is exceedingly rare; focus on identifying and treating secondary causes 4
By following this structured approach to thrombocytosis workup and management, clinicians can effectively identify the underlying cause and implement appropriate treatment strategies to reduce complications and improve outcomes.