What is the initial step in the workup of a patient presenting with thrombocytosis (elevated platelet count)?

Initial Workup of Thrombocytosis

The initial step in the workup of a patient presenting with thrombocytosis should be to distinguish between primary (clonal) and secondary (reactive) causes through a complete blood count with peripheral blood smear examination, inflammatory markers, and iron studies. 1

Diagnostic Algorithm

Step 1: Initial Laboratory Assessment

• Complete blood count with peripheral blood smear examination
  • Look for abnormal platelet morphology, giant platelets, or other cell line abnormalities
  • Assess for leukocytosis, anemia, or other hematologic abnormalities
• Basic inflammatory markers: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)
• Iron studies: ferritin, transferrin saturation
• Renal and liver function tests

Step 2: Clinical Assessment for Secondary Causes

Secondary (reactive) thrombocytosis accounts for the majority of cases and should be ruled out first:

• Inflammatory conditions (check CRP/ESR)
• Iron deficiency (check ferritin, transferrin saturation)
• Recent infection
• Post-surgical state or trauma
• Malignancy (consider age-appropriate cancer screening)
• Medication-induced
• Post-splenectomy state
• Recent COVID-19 vaccination

Step 3: If Secondary Causes Are Not Identified

If no secondary cause is found and thrombocytosis persists:

• JAK2 V617F mutation testing (most common mutation in primary thrombocytosis)
• If JAK2 negative, consider testing for CALR and MPL mutations
• Bone marrow examination with cytogenetic studies

Special Considerations

When to Suspect Primary Thrombocytosis

• Persistent thrombocytosis without obvious secondary cause
• History of thrombotic events
• Splenomegaly
• Abnormal blood cell morphology on peripheral smear
• Family history of myeloproliferative disorders

Risk Factors That May Indicate Primary Thrombocytosis

• History of arterial thrombosis is particularly suggestive of essential thrombocythemia 2
• Higher mean platelet volume (MPV) and red cell distribution width (RDW) are associated with primary thrombocytosis 2

Factors More Suggestive of Secondary Thrombocytosis

• Active malignancy
• Chronic inflammatory disease
• Recent splenectomy
• Iron deficiency anemia
• Higher white blood cell and neutrophil counts 2

Treatment Considerations

Treatment depends on the underlying cause:

• For secondary thrombocytosis: treat the underlying condition
• For primary thrombocytosis: risk stratification for thrombotic complications and consideration of cytoreductive therapy and antiplatelet agents

Pitfalls to Avoid

1. Overinvestigation: Not all patients with thrombocytosis require extensive molecular testing. Consider clinical context first.
2. Missing secondary causes: Thoroughly investigate for common secondary causes before pursuing workup for primary thrombocytosis.
3. Ignoring persistent thrombocytosis: If thrombocytosis persists after addressing potential secondary causes, further evaluation is warranted.
4. Overlooking thrombotic risk: Even with secondary thrombocytosis, patients with very high platelet counts (>1,000/mm³) may require intervention to prevent complications 3.

By following this systematic approach, clinicians can efficiently differentiate between primary and secondary thrombocytosis, leading to appropriate management decisions and avoiding unnecessary testing.