What is the management and additional testing for a patient with thrombocytosis (elevated platelet count)?

Management of Thrombocytosis: Therapeutic Blood Draw and Additional Testing

Therapeutic phlebotomy is indicated for patients with thrombocytosis due to polycythemia vera or other myeloproliferative neoplasms to reduce thrombotic risk, but is not a standard treatment for isolated thrombocytosis from other causes.

Patient Education About Therapeutic Blood Draw

When discussing therapeutic blood draw (phlebotomy) with patients who have elevated platelets, explain:

• Therapeutic phlebotomy is primarily used for polycythemia vera to maintain hematocrit <45%, not for isolated thrombocytosis 1
• The procedure involves removing approximately 450-500mL of blood (similar to blood donation)
• The goal is to reduce blood viscosity and thrombotic risk, not directly reduce platelet count
• Frequency depends on individual response, typically every 2-4 weeks initially, then less frequently
• Common side effects include lightheadedness, fatigue, and potential iron deficiency with repeated procedures
• This is different from plateletpheresis, which may be used only in emergencies with extreme thrombocytosis causing acute life-threatening thrombosis 1

Diagnostic Approach for Elevated Platelets

Step 1: Determine if thrombocytosis is primary or secondary

• Primary thrombocytosis (12.5% of cases) 2:

  • Myeloproliferative neoplasms (essential thrombocythemia, polycythemia vera, primary myelofibrosis)
  • Usually persistent elevation
  • Higher risk of thrombotic complications

• Secondary/reactive thrombocytosis (83.1% of cases) 2:

  • Common causes: tissue injury (32.2%), infection (17.1%), chronic inflammatory disorders (11.7%), iron deficiency anemia (11.1%)
  • Usually transient and resolves when underlying condition is treated

Step 2: Essential laboratory testing

1. Complete blood count with peripheral smear

   • Evaluate for other cytopenias or abnormal cells
   • Assess platelet morphology

2. Iron studies

   • Ferritin, iron, TIBC, transferrin saturation
   • Iron deficiency is a common cause of reactive thrombocytosis

3. Inflammatory markers

   • ESR, CRP to assess for inflammatory conditions
   • Elevated in reactive thrombocytosis

4. Molecular testing for JAK2V617F mutation

   • Present in 50-60% of essential thrombocythemia cases
   • Present in >95% of polycythemia vera cases
   • Helps distinguish primary from secondary thrombocytosis

5. Additional genetic testing if JAK2 negative

   • CALR and MPL mutations (found in ~25% and ~5% of ET cases respectively)
   • These mutations are found in 86% of primary thrombocytosis cases 2

Step 3: Specialized testing based on clinical suspicion

• Bone marrow biopsy and aspiration

  • Required to confirm diagnosis of myeloproliferative neoplasm
  • Essential for diagnosing essential thrombocythemia
  • Evaluates megakaryocyte morphology and clonality

• Coagulation studies

  • If bleeding symptoms present
  • Assess for acquired von Willebrand disease which can occur with extreme thrombocytosis 1

• D-dimer and other thrombosis markers

  • If thrombosis is suspected
  • D-dimer >4000 μg/mL may indicate thrombotic complications 1

Management Considerations

Risk stratification for thrombosis

• High risk factors:
  • Age >60 years
  • Prior thrombotic event
  • Platelet count >1,000/μL
  • Cardiovascular risk factors (hypertension, diabetes, smoking)
  • JAK2V617F mutation positivity

Treatment approach

• For primary thrombocytosis:

  • Low-dose aspirin for thrombosis prevention in most patients
  • Cytoreductive therapy (hydroxyurea, interferon) for high-risk patients
  • Monitor for both thrombotic and bleeding complications

• For secondary thrombocytosis:

  • Treat underlying cause
  • Usually self-limiting and rarely requires specific platelet-lowering therapy
  • Rarely associated with thrombotic complications

Special Considerations

• Cancer screening if unexplained persistent thrombocytosis, as it may be a paraneoplastic phenomenon
• Vaccine-induced immune thrombocytopenia and thrombosis (VITT) should be considered in patients with recent COVID-19 vaccination (5-30 days) who present with thrombocytopenia and thrombosis 1
• Plateletpheresis is reserved only for patients with acute life-threatening thrombosis or severe bleeding 1

Remember that while primary thrombocytosis carries significant thrombotic risk, secondary thrombocytosis rarely leads to complications and typically resolves with treatment of the underlying condition.