Initial Approach to Managing Thrombocytosis
The initial management of thrombocytosis requires first distinguishing between primary (clonal) and secondary (reactive) causes, as this fundamentally determines treatment strategy—primary thrombocytosis requires risk-stratified cytoreductive therapy to prevent thrombosis, while secondary thrombocytosis is managed by addressing the underlying condition. 1, 2
Diagnostic Differentiation: Primary vs Secondary Thrombocytosis
Clinical factors strongly predictive of secondary thrombocytosis include:
- Active malignancy 2
- Chronic inflammatory disease 3, 2
- History of splenectomy 2
- Iron deficiency anemia 3, 2
- Tissue injury (32.2% of secondary cases) 3
- Active infection (17.1% of secondary cases) 3
Clinical factors predictive of primary thrombocytosis (essential thrombocythemia):
- History of arterial thrombosis 2
- Higher hemoglobin, mean corpuscular volume (MCV), red cell distribution width (RDW), and mean platelet volume (MPV) 2
- Platelet counts typically higher than secondary causes (median significantly elevated) 3
Laboratory workup for suspected primary thrombocytosis:
- JAK2V617F mutation testing (present in ~60% of essential thrombocythemia) 4, 5
- CALR and MPL mutation testing if JAK2 negative (collectively 80% of patients harbor driver mutations) 5
- Bone marrow biopsy showing increased mature-appearing megakaryocytes in loose clusters 5
- Complete blood count with differential 2
- Ferritin level to exclude iron deficiency 2
Risk Stratification for Primary Thrombocytosis
Once essential thrombocythemia is confirmed, assign patients to thrombotic risk categories:
Very low risk: Age ≤60 years, no thrombosis history, JAK2 wild-type 5
Low risk: Age ≤60 years, no thrombosis history, JAK2 mutation present 5
Intermediate risk: Age >60 years, no thrombosis history, JAK2 wild-type 5
High risk: History of thrombosis at any age OR age >60 years with JAK2 mutation 6, 5
Treatment Algorithm Based on Risk Category
High-Risk Patients (History of Thrombosis or Age >60 with JAK2 Mutation)
Initiate cytoreductive therapy with hydroxyurea as first-line agent 6, 5
Add once-daily low-dose aspirin (40-325 mg) if platelet count <1,500 × 10⁹/L 6, 5
If hydroxyurea is not tolerated, use pegylated interferon-α or anagrelide as alternatives 6, 5
Intermediate-Risk Patients (Age >60, No Thrombosis, JAK2 Wild-Type)
Cytoreductive therapy is optional; consider based on additional cardiovascular risk factors 5
Once-daily low-dose aspirin is advised for all patients 5
Low-Risk and Very Low-Risk Patients
Once-daily low-dose aspirin for low-risk (JAK2-mutated) patients 5
Twice-daily low-dose aspirin for very low-risk (JAK2 wild-type) patients 5
Observation without cytoreductive therapy is appropriate 6, 5
Exception: If platelet count >1,500 × 10⁹/L, consider cytoreductive therapy even in low-risk patients due to paradoxical bleeding risk 6
Management of Secondary Thrombocytosis
Address the underlying cause (infection, inflammation, malignancy, iron deficiency) 3, 2
No cytoreductive therapy is indicated for secondary thrombocytosis 3
Thrombosis risk is significantly lower than primary thrombocytosis 3
Platelet counts typically normalize once underlying condition is treated 3
Critical Pitfalls to Avoid
Do not initiate cytoreductive therapy based solely on platelet count elevation without confirming primary thrombocytosis 3, 2
Do not use aspirin if platelet count ≥1,500 × 10⁹/L due to acquired von Willebrand syndrome and paradoxical bleeding risk 6, 5
Do not overlook bone marrow biopsy when molecular testing is negative but clinical suspicion for myeloproliferative neoplasm remains high 4, 5
Avoid overinvestigation with costly next-generation sequencing in patients with clear secondary causes (active malignancy, chronic inflammation, splenectomy, iron deficiency) 2
Special Populations
Pregnant patients with high-risk essential thrombocythemia: Use interferon-α as the cytoreductive agent of choice (hydroxyurea is teratogenic) 6, 5
Patients requiring anticoagulation: Full therapeutic anticoagulation can be safely administered with platelet counts >50 × 10⁹/L 1, 7