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

Workup for Thrombocytosis

The workup for thrombocytosis (platelet count >450×10^9/L) should begin with a thorough clinical evaluation to distinguish between primary (clonal) and secondary (reactive) causes, followed by targeted laboratory testing based on initial findings. 1, 2

Initial Assessment

• Complete blood count (CBC) with peripheral blood smear examination by a qualified hematologist or pathologist to evaluate platelet morphology and exclude pseudothrombocytosis due to EDTA-dependent platelet agglutination 1

• Comprehensive clinical history focusing on:

  • Personal and family history of bleeding or thrombotic events 1
  • Presence of constitutional symptoms (fever, weight loss) 1
  • Recent tissue injury, surgery, or infection 2
  • Medication review 1
  • Symptoms of chronic inflammatory disorders 2

• Physical examination to assess for:

  • Splenomegaly (suggests myeloproliferative neoplasm) 1
  • Lymphadenopathy (suggests lymphoproliferative disease) 1
  • Signs of chronic inflammation or infection 2
  • Evidence of bleeding or thrombosis 3

Laboratory Investigations

First-line Tests

• Complete blood count with differential 1
• Peripheral blood smear examination to evaluate platelet morphology and exclude pseudothrombocytosis 1
• Basic coagulation studies (PT, aPTT) 1
• Iron studies (serum ferritin, transferrin saturation) to rule out iron deficiency 2, 4
• Inflammatory markers (ESR, CRP) to assess for inflammatory conditions 2
• Liver function tests 5

Second-line Tests (Based on Initial Findings)

• JAK2 V617F mutation analysis - essential for evaluation of suspected myeloproliferative neoplasms 1, 4
• CALR and MPL mutation testing if JAK2 negative but clinical suspicion for myeloproliferative neoplasm remains high 4
• HIV and HCV testing - recommended in all adult patients with suspected primary thrombocytosis 1
• Helicobacter pylori testing - consider in adults where it may have clinical impact 1
• Bone marrow aspiration and biopsy with cytogenetic testing and flow cytometry when:
  • Age >60 years with unexplained thrombocytosis 1
  • Abnormal findings on peripheral blood smear 1
  • Suspected myeloproliferative disorder 1
  • Before splenectomy is considered 1

Diagnostic Algorithm

1. Confirm true thrombocytosis (platelet count >450×10^9/L) and exclude pseudothrombocytosis by repeating CBC with a citrate or heparin tube if necessary 1, 5

2. Evaluate for secondary causes of thrombocytosis:

   • Acute or chronic inflammation 2
   • Infection 2
   • Iron deficiency anemia 2, 4
   • Recent surgery or tissue injury 2
   • Malignancy 2, 4
   • Post-splenectomy 4

3. If secondary causes are excluded or clinical suspicion for primary thrombocytosis exists, proceed with:

   • JAK2 V617F mutation testing 1
   • If JAK2 negative, test for CALR and MPL mutations 4
   • Bone marrow examination with cytogenetics 1

4. Apply WHO diagnostic criteria for essential thrombocythemia if primary thrombocytosis is suspected:

   • Sustained platelet count ≥450×10^9/L 1
   • Bone marrow biopsy showing proliferation mainly of megakaryocytic lineage 1
   • Not meeting WHO criteria for other myeloid neoplasms 1
   • Demonstration of JAK2, CALR, or MPL mutation, or in their absence, no evidence of reactive thrombocytosis 1

Special Considerations

• Thrombotic risk assessment is essential in patients with confirmed primary thrombocytosis 1, 3
• Secondary thrombocytosis (platelet count >500×10^9/L) is common but benign in children with infections; antiplatelet therapy is not necessary 1
• Paradoxical complications of both bleeding and thrombosis can occur in patients with essential thrombocythemia 3, 6
• Molecular testing yield is approximately 52.4% in patients with thrombocytosis, with 92.1% of positive results being mutations in JAK2, CALR, or MPL 4

Common Pitfalls to Avoid

• Overlooking secondary causes - approximately 83% of thrombocytosis cases are secondary rather than primary 2
• Unnecessary bone marrow examination in patients with obvious secondary causes 1
• Failure to test for JAK2 V617F mutation in suspected myeloproliferative disorders 1
• Misdiagnosing essential thrombocythemia in patients with reactive thrombocytosis due to iron deficiency, inflammation, or malignancy 2, 4
• Overlooking thrombotic risk in patients with primary thrombocytosis 1, 3