What is the workup for thrombocytosis?

Workup for Thrombocytosis

Begin with a complete blood count (CBC) with peripheral blood smear examination by a qualified hematologist or pathologist to confirm true thrombocytosis (platelet count ≥450×10⁹/L) and exclude pseudothrombocytosis from EDTA-dependent platelet agglutination. 1, 2

Initial Clinical Assessment

History should focus on:

• Personal and family history of bleeding or thrombotic events 1
• Constitutional symptoms (fever, weight loss, night sweats) suggesting myeloproliferative neoplasm or malignancy 2
• Medication review including over-the-counter products 3
• Recent infections, tissue injury, surgery, or chronic inflammatory conditions 4
• Iron deficiency symptoms 4

Physical examination must assess for:

• Splenomegaly (mild splenomegaly may occur in younger patients with primary thrombocytosis; moderate/massive suggests alternative diagnosis) 2, 1
• Hepatomegaly or lymphadenopathy (suggests lymphoproliferative disease) 2
• Signs of chronic inflammation or infection 1

Laboratory Investigations

First-line tests include: 1

• CBC with differential and peripheral blood smear 2, 1
• Basic coagulation studies (PT, aPTT) 2, 1
• JAK2 V617F mutation analysis (essential for suspected myeloproliferative neoplasms) 1, 5

Additional testing based on clinical suspicion:

• Iron studies if iron deficiency suspected 4
• Inflammatory markers (CRP, ESR) if chronic inflammation suspected 4
• Imaging studies if malignancy or tissue injury suspected 4

Distinguishing Primary from Secondary Thrombocytosis

Secondary thrombocytosis is far more common (83% of cases) and major causes include: 4

• Tissue injury (32.2%)
• Infection (17.1%)
• Chronic inflammatory disorders (11.7%)
• Iron deficiency anemia (11.1%)

Primary thrombocytosis features: 4, 5

• Higher median platelet counts (often >600×10⁹/L)
• Significantly higher incidence of thrombosis
• 86% have at least one molecular marker (JAK2, CALR, or MPL mutation) 4

Bone Marrow Examination Indications

Bone marrow aspiration and biopsy with cytogenetic testing and flow cytometry are indicated when: 1, 2

• Age >60 years with unexplained thrombocytosis
• Abnormal findings on peripheral blood smear
• Systemic symptoms present
• Suspected myeloproliferative disorder
• No obvious secondary cause identified

Avoid unnecessary bone marrow examination when obvious secondary causes are present (infection, recent surgery, iron deficiency). 1

WHO Diagnostic Criteria for Essential Thrombocythemia

All four criteria must be met: 1

1. Sustained platelet count ≥450×10⁹/L
2. Bone marrow biopsy showing proliferation mainly of megakaryocytic lineage
3. Demonstration of JAK2, CALR, or MPL mutation, OR in their absence, no evidence of reactive thrombocytosis
4. Exclusion of other myeloid neoplasms

Risk Stratification

Thrombotic risk assessment is essential in confirmed primary thrombocytosis. 1 Patients with primary thrombocytosis and thrombosis have significantly higher reticulated platelet percentages (14.7% vs 3.4% in asymptomatic patients) and absolute reticulated platelet counts (98×10⁹/L vs 30×10⁹/L), indicating increased platelet turnover. 6

Special Considerations

In children: Secondary thrombocytosis with platelet count >500×10⁹/L is common but benign with infections, and antiplatelet therapy is not necessary. 1 Primary thrombocytosis is extremely rare (1 per million children). 7

Common pitfalls to avoid:

• Failing to exclude pseudothrombocytosis before extensive workup 3
• Missing secondary causes (infection, inflammation, iron deficiency, malignancy) 3
• Delaying bone marrow examination in older patients where myelodysplastic syndromes are more common 3