Workup for Thrombocytosis (Elevated Platelet Count)
The diagnostic workup for thrombocytosis should first distinguish between primary (clonal) and secondary (reactive) causes, as this fundamentally determines management and prognosis.
Initial Assessment
- Confirm true thrombocytosis: Collect blood in a tube containing heparin or sodium citrate to exclude pseudothrombocytopenia 1
- Review previous platelet counts: Determine if thrombocytosis is acute or chronic
- Complete blood count with differential: Assess for abnormalities in other cell lines
- Peripheral blood smear: Evaluate platelet morphology and other cell abnormalities
Distinguishing Primary vs. Secondary Thrombocytosis
Secondary (Reactive) Thrombocytosis (83.1% of cases) 2
Evaluate for common causes:
- Inflammation/Infection (17.1% of secondary cases)
- Check CRP, ESR, procalcitonin
- Evaluate for bacterial/viral infections
- Tissue injury/Surgery (32.2% of secondary cases)
- Recent surgical history
- Trauma assessment
- Iron deficiency anemia (11.1% of secondary cases)
- Check ferritin, iron, TIBC, transferrin saturation
- Chronic inflammatory disorders (11.7% of secondary cases)
- Assess for autoimmune conditions, inflammatory bowel disease
- Malignancy
- Age-appropriate cancer screening
- Post-splenectomy or hyposplenism
- Review surgical history
- Assess for Howell-Jolly bodies on peripheral smear
Primary Thrombocytosis (12.5% of cases) 2
If secondary causes excluded, evaluate for myeloproliferative neoplasms (MPNs):
- Molecular testing:
- JAK2V617F mutation (most common)
- MPLW515L/K mutations
- CALR mutations
- Bone marrow examination: Essential for diagnosis of MPNs
- Aspiration and biopsy
- Cytogenetic studies
- Assessment of megakaryocyte morphology
Risk Assessment for Thrombotic Complications
For primary thrombocytosis (especially essential thrombocythemia):
- Age (>60 years increases risk)
- Prior history of thrombosis (significant risk factor)
- Cardiovascular risk factors (hypertension, diabetes, hyperlipidemia)
- Leukocytosis (associated with increased thrombotic risk)
- JAK2V617F mutation status (positive status increases thrombotic risk)
Management Considerations
For Secondary Thrombocytosis:
- Treat underlying cause
- Generally lower risk of thrombotic complications than primary thrombocytosis
For Primary Thrombocytosis (Essential Thrombocythemia):
- Low-risk patients: Consider aspirin (81-100 mg/day) 3
- High-risk patients (age >60 years and/or prior history of thrombosis):
- Cytoreductive therapy (hydroxyurea first-line)
- Aspirin therapy
- Management of cardiovascular risk factors 3
Special Considerations
- Patients with platelet counts <50 × 10³/μL should adhere to activity restrictions to avoid trauma-associated bleeding 1
- Patients with newly diagnosed immune thrombocytopenia should undergo testing for HIV, HCV, HBV, and H. pylori 3
- For patients with primary thrombocytosis and platelet counts >1,000 × 10⁹/L, paradoxically assess for bleeding risk due to acquired von Willebrand syndrome
Follow-up
- For suspected primary thrombocytosis: Hematology referral within 24-72 hours 3
- For secondary thrombocytosis: Monitor platelet counts until resolution of underlying condition
By systematically following this approach, clinicians can efficiently determine the cause of thrombocytosis and implement appropriate management strategies to reduce complications.