What tests should be ordered for a patient with suspected thrombocytosis (elevated platelet count)?

Diagnostic Workup for Suspected Thrombocytosis

For a patient with suspected thrombocytosis (elevated platelet count), a complete blood count (CBC) with peripheral blood smear should be ordered first, followed by targeted testing based on initial results to determine whether the thrombocytosis is primary (clonal) or secondary (reactive). 1

Initial Laboratory Evaluation

• Complete blood count (CBC) - Essential first test to confirm thrombocytosis (platelet count ≥450×10^9/L) 2
• Peripheral blood smear - To assess platelet morphology and identify potential causes of thrombocytosis 1
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) - To evaluate coagulation status 1

Secondary Testing Based on Initial Results

If thrombocytosis is confirmed (platelet count ≥450×10^9/L):

Tests to differentiate between primary and secondary thrombocytosis:

• Serum ferritin - Iron deficiency is a common cause of secondary thrombocytosis 3
• C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) - Elevated in inflammatory conditions causing secondary thrombocytosis 2
• Molecular testing for myeloproliferative neoplasm mutations:
  • JAK2 V617F mutation
  • CALR mutation
  • MPL mutation 3

Additional laboratory tests:

• Complete metabolic panel - To assess for underlying organ dysfunction 1
• Reticulocyte count - To evaluate for hemolysis or blood loss 1
• D-dimer - To assess for thrombotic risk, particularly important if platelet count is extremely elevated (>1,000×10^9/L) 4

Specialized Testing for Suspected Primary Thrombocytosis

If initial evaluation suggests primary thrombocytosis or if secondary causes are ruled out:

• Bone marrow aspiration and biopsy with cytogenetic analysis - Gold standard for diagnosing myeloproliferative disorders 5
• Next-generation sequencing (NGS) panel - For detection of less common mutations associated with myeloproliferative neoplasms 3

Additional Considerations

For suspected secondary thrombocytosis:

• Inflammatory marker panel - To identify underlying chronic inflammatory disorders 2
• Iron studies (serum iron, total iron binding capacity, transferrin saturation) - To confirm iron deficiency 3
• Blood cultures - If infection is suspected 2
• Imaging studies - Based on clinical suspicion of underlying malignancy or inflammatory condition 3

For suspected vaccine-induced immune thrombocytosis and thrombosis (VITT):

• Anti-PF4 antibody ELISA - If thrombocytosis is associated with thrombosis following COVID-19 vaccination 1
• Fibrinogen level - To assess for consumptive coagulopathy 1

Common Pitfalls and Caveats

• Thrombocytosis is more commonly secondary (83.1%) than primary (12.5%), so always rule out reactive causes before pursuing extensive hematologic workup 2
• Extreme thrombocytosis (≥1,000×10^9/L) requires urgent evaluation as it carries higher risk of both thrombotic and hemorrhagic complications 4
• Patients with autoimmune disorders (particularly SLE with antiphospholipid antibodies) may develop functional autosplenectomy leading to thrombocytosis - check peripheral smear for Howell-Jolly bodies 6
• Avoid unnecessary molecular testing in patients with clear secondary causes of thrombocytosis (active malignancy, chronic inflammatory disease, recent splenectomy, or iron deficiency) 3
• Patients with thrombocytosis and bleeding symptoms should have platelet function testing to rule out acquired or inherited platelet function disorders 1