What is the workup for thrombocytosis (elevated platelet count)?

Workup for Thrombocytosis

The diagnostic workup for thrombocytosis should begin with distinguishing between primary (clonal) and secondary (reactive) causes, as this fundamentally determines management and prognosis.

Initial Evaluation

• Complete blood count (CBC) with peripheral blood smear to confirm thrombocytosis (platelet count >450 × 10^9/L) 1
• Review of medication list to identify drugs that may cause thrombocytosis
• Inflammatory markers: ESR, CRP to assess for inflammatory conditions
• Iron studies: Serum ferritin, iron, TIBC to rule out iron deficiency 2
• Renal and liver function tests to evaluate for underlying organ dysfunction

Distinguishing Primary vs. Secondary Thrombocytosis

Secondary (Reactive) Thrombocytosis

Secondary thrombocytosis accounts for approximately 83% of cases 3 and should be ruled out first:

• Infection: Acute or chronic infections
• Inflammation: Chronic inflammatory disorders (11.7% of cases) 3
• Tissue injury: Most common cause (32.2% of cases) 3
• Iron deficiency anemia: Common cause (11.1% of cases) 3
• Post-surgical state
• Malignancy: Solid tumors can cause paraneoplastic thrombocytosis
• Post-splenectomy
• Medications: Corticosteroids, epinephrine, vincristine

Primary Thrombocytosis Workup

If secondary causes are excluded or platelet count remains persistently elevated:

1. Molecular testing:

   • JAK2 V617F mutation testing (first-line)
   • If JAK2 negative, proceed with CALR and MPL mutation testing 2
   • 86% of primary thrombocytosis cases have at least one molecular marker 3

2. Bone marrow aspiration and biopsy:

   • Essential for diagnosis of myeloproliferative neoplasms
   • Assess megakaryocyte morphology and number
   • Look for increased numbers of enlarged, mature megakaryocytes 1

3. Cytogenetic studies:

   • To rule out other myeloid neoplasms 2
   • Philadelphia chromosome testing to exclude CML

Diagnostic Criteria for Essential Thrombocythemia

According to the revised WHO criteria, diagnosis of essential thrombocythemia requires all 4 criteria 1:

1. Sustained platelet count ≥450 × 10^9/L
2. Bone marrow biopsy showing proliferation mainly of megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes
3. Not meeting WHO criteria for other myeloproliferative neoplasms (PV, PMF, CML), MDS, or other myeloid neoplasms
4. Presence of JAK2, CALR, or MPL mutation OR in absence of these mutations, no evidence for reactive thrombocytosis

Risk Stratification

For confirmed primary thrombocytosis, risk stratification is essential:

• High risk: Age >60 years and/or history of thrombosis 1
• Low risk: Age ≤60 years with no history of thrombosis 1
• Very low risk: Age ≤60 years, no JAK2 mutation, no prior thrombosis 1

Special Considerations

• Extreme thrombocytosis (>1,000 × 10^9/L) may paradoxically increase bleeding risk due to acquired von Willebrand syndrome
• Secondary thrombocytosis in children is common and benign in 72-86% of cases 4
• Pregnancy: Special management considerations required if essential thrombocythemia is diagnosed 2

When to Refer to Hematology

• Persistent unexplained thrombocytosis
• Platelet count >1,000 × 10^9/L
• Presence of symptoms (bleeding or thrombosis)
• Confirmed or suspected primary thrombocytosis

Remember that primary thrombocytosis carries a significantly higher risk of thrombotic complications compared to secondary thrombocytosis 3, making accurate diagnosis crucial for proper management and prevention of morbidity and mortality.